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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-000322-35 | EudraCT Number | ||
| U1111-1197-1202 | Registry Identifier | WHO |
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This is a Phase 2, multicenter, open-label study to evaluate the efficacy and safety of luspatercept in subjects with MPN-associated myelofibrosis and anemia with and without RBC-transfusion dependence. The study is divided into a Screening Period, a Treatment Period (consisting of a Primary Phase, a Day 169 Disease Response Assessment, and an Extension Phase), followed by a Posttreatment Follow-up Period.
Subjects satisfying the eligibility criteria will be assigned to 1 of the following cohorts (which are enrolling in parallel) based on their eligibility:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Luspatercept in subjects with MPN-associated myelofibrosis | Experimental | Subjects across each of the cohorts (Cohort 1, Cohort 2, Cohort 3A, and Cohort 3B) will receive luspatercept. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Luspatercept | Drug | Luspatercept is a recombinant fusion protein consisting of a modified form of the extracellular domain of the human active in receptor type IIB linked to the IgG1 Fc domain. Luspatercept, through a mechanism of action different from erythropoietin, works to correct ineffective erythropoiesis by promoting late-stage maturation of erythroblasts. |
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Participants With Anemia Responses Over Any 84-Day Period During the Primary Treatment Period | The number of participants that achieved anemia response as it relates to hemoglobin (Hgb) increase and red blood cell (RBC)-transfusion independence is defined below: Cohorts 1 (anemia only) and 3A: The number of participants achieving ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion from Day 1 up through and including Day 168. Cohorts 2 (RBC-transfusion dependent) and 3B: The number of participants who become RBC-transfusion free over any consecutive 84-day period from Day 1 up through and including Day 168. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose. | Any consecutive "rolling" 84-day period from Day 1 through and including Day 168 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Anemia Response During the Primary Treatment Period | Time to anemia response follows the definitions below: Cohorts 1 (anemia only) and 3A: Time between first administration of luspatercept and the first hemoglobin increase of ≥ 1.5 g/dL from baseline that starts a consecutive 84-day period of consecutive increase ≥ 1.5 g/dL without RBC transfusions. Cohorts 2 (RBC-transfusion dependent) and 3B: Time between first administration of luspatercept and the first day of an RBC transfusion-free period of 84 days. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose. |
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Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study (with the enrollment date defined as the date in which the subject is assigned a cohort in Integrated Response Technology [IRT]) and receive their first dose of luspatercept:
Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
Subject has Myeloproliferative neoplasm (MPN)-associated myelofibrosis (PMF, post- Post-polycythemia vera myelofibrosis (PV MF), and/or Post-essential thrombocythemia myelofibrosis (post-ET MF)) as confirmed from the most recent local bone marrow biopsy report according to the World Health Organization 2016 criteria.
Subject has anemia defined as:
Cohorts 1 and 3A
Cohorts 2 and 3B
Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
Subject is not anticipated during the 6 months from the C1D1 date to receive a hematopoietic cell transplant.
A female of childbearing potential (FCBP) for this study is defined as a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). FCBP participating in the study must:
Male subjects must:
a. Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal half-life of luspatercept based on multiple-dose PK data) following investigational product discontinuation, even if he has undergone a successful vasectomy
Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment (with the enrollment date defined as the date in which the subject is assigned a cohort in Integrated Response Technology (IRT)):
Subject use of hydroxyurea or other drugs with potential effects on hematopoiesis or ongoing adverse events from previous treatment ≤ 112 days immediately up to the enrollment date.
a. Systemic corticosteroids are permitted for nonhematological conditions providing the subject is receiving a stable or decreasing dose for ≥ 84 days immediately up to enrollment and is receiving a constant dose equivalent to ≤ 10 mg prednisone for the 28 days immediately up to enrollment.
Cohort 1 and 2 only: subjects treated with Janus kinase 2 gene (JAK2) inhibitors ≤ 112 days immediately up to the enrollment date or if anticipated/substantial likelihood for subject to receive ruxolitinib within the first 168 days on the study.
Cohort 3 only: subjects not receiving ruxolitinib:
Subject use of ESAs or androgenic steroids ≤ 112 days immediately up to the enrollment date.
Initiation of iron chelation therapy (ICT) or change with ICT dose within ≤ 112 days up to the enrollment date.
Subject with anemia from iron deficiency, B12 and folate deficiencies, hemolytic anemia, infection, or bleeding.
Pregnant or breastfeeding females.
Subject with blood myeloblasts ≥ 5%.
Subject with major surgery within 8 weeks up to the enrollment date. Subject must have completely recovered from any previous surgery immediately up to the enrollment date.
Subject with prior history of malignancies, other than disease under study, unless the subject has been free of the disease for ≥ 5 years. However, subject with the following history/concurrent conditions is allowed:
Subject with prior therapy of luspatercept or sotatercept.
Subject participation in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices within 30 days immediately up to the enrollment date.
Subject with prior hematopoietic cell transplant.
Subject with any of the following laboratory abnormalities:
Neutrophils < 1 x 109/L
White blood count (WBC) > 100 x 109/L
Platelets
Estimated glomerular filtration rate < 45 mL/min/1.73 m2 (via the 4-variable modification of diet in renal disease [Modification of diet in renal disease (MDRD)] formula)
Aspartate aminotransferase (AST) or alanine transaminase (ALT) > 3.0 x upper limit of normal (ULN)
Direct bilirubin ≥ 2 x ULN
Uncontrolled hyperthyroidism or hypothyroidism
Subject with stroke, deep venous thrombosis, pulmonary or arterial embolism within 6 months immediately up to the enrollment date.
Subject with diastolic blood pressure ≥ 90 mmHg or systolic blood pressure ≥ 140 mmHg measured during the Screening Period despite appropriate treatment.
Subject with inadequately controlled heart disease and/or have a known left ventricular ejection fraction <35%.
Subject with history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see luspatercept Investigator's Brochure (IB)).
Subject with uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
Subject with human immunodeficiency virus (HIV), evidence of active infectious Hepatitis B (HepB), and/or evidence of active Hepatitis C (HepC).
Subject with any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that would prevent the subject from participating in the study.
Subject with any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
Subject with any condition or concomitant medication that confounds the ability to interpret data from the study.
Subject on anticoagulant therapy not under appropriate control or subject not on a stable dose of anticoagulant therapy for ≥ 8 weeks up to the enrollment date.
Subject on anagrelide within 28 days immediately up to the enrollment date.
Subject with a major bleeding event (defined as symptomatic bleeding in a critical area or organ and/or bleeding causing a decrease in hemoglobin of ≥ 2g/dL or leading to transfusion of ≥ 2 units of packed red cells) in the last 6 months prior to enrollment.
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Local Institution - 102 | Phoenix | Arizona | 85054 | United States | ||
| Mayo Clinic - Arizona |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38820422 | Derived | Gerds AT, Harrison C, Kiladjian JJ, Mesa R, Vannucchi AM, Komrokji R, Bose P, Kremyanskaya M, Mead AJ, Gotlib J, Rose S, Sanabria F, Marsousi N, Giuseppi AC, Jiang H, Palmer JM, McCaul K, Ribrag V, Passamonti F. Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis. Blood Adv. 2024 Sep 10;8(17):4511-4522. doi: 10.1182/bloodadvances.2024012939. |
| Label | URL |
|---|---|
| BMS Clinical Trial Information | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: Anemia Only | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 19, 2020 |
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| From first dose up to first onset of anemia response (calculated from Day 1 through and including Day 168) |
| Duration of Anemia Response | The duration of anemia response is defined as the duration of time from first day of longest response to the last day of longest response. Participants who achieved and maintained the anemia response at the time of the analysis are censored at the efficacy cutoff date. For Cohorts 1 and 3A, an anemia responder was defined as a subject with ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion. For Cohorts 2 and 3B, an anemia responder was defined as a subject who becomes RBC transfusion free over any consecutive 84-day period. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose. | From first dose through last day of longest response (calculated from Day 1 through end of treatment, up to approximately 232 weeks) |
| The Number of RBC Units Transfused Per Participant Per 28 Days (Cohorts 2 and 3B Only) | Frequency of RBC transfusion is defined as the mean number of RBC units transfused per participant every 4 weeks (28 days). The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. | From Day 1 through end of treatment (up to approximately 232 weeks). |
| The Number Participants Achieving >=50% RBC Transfusion Burden Reduction From Baseline Over Any 84-Day Period (Cohorts 2 and 3B Only) | The number of participants who reduce their transfusion burden by ≥ 50% from baseline over any consecutive 84-day period. Baseline is defined as average number of RBC units per 28 days over the 84 days period on or prior to the C1D1 date. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. | Baseline and from Day 1 through end of treatment (up to approximately 232 weeks). |
| The Number of Participants Who Achieve ≥ 50% Reduction in Fatigue Symptom as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Symptoms response improvement will be assessed using the number of participants who achieve ≥ 50% reduction in fatigue symptoms. Fatigue is 1 out of 10 total symptoms scored on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as the last value on or before the first dose of study drug. Last Available = Last available assessment on or before the end of the treatment period. Mean = Mean value of the weekly assessments over the treatment period. | Baseline and from Day 1 through end of treatment (up to approximately 232 weeks) |
| The Number of Participants Who Achieve ≥ 50% Reduction in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | TSS includes 10 items - worst fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers, scored on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). For participants who completed at least six of these 10 items, the MPN-SAF TSS was computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus had a possible range of 0 to 100. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as the last value on or before the first dose of study drug. Last Available = Last available assessment on or before the end of the treatment period. Mean = Mean value of the weekly assessments over the treatment period. | Baseline and from Day 1 through end of treatment (up to approximately 232 weeks) |
| Mean Changes in the Functional Assessment of Cancer Therapy - Anemia (FACT-An) Total Scores Over the Study Compared to Baseline | The Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire includes 47 items rating on a 5-point Likert scale from 0 (not at all) to 4 (very much) on five primary subscales:
A total score for the FACT-An can be calculated by summing the five primary subscales with a score range from 0-188. Higher scores representing better quality of life. Baseline is defined as the last value on or before the first dose of study drug. | Day 169 and End of treatment (up to approximately 232 weeks) |
| Mean Change in EQ-5D-5L Utility Score Compared to Baseline | The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index for this analysis will be derived using the United Kingdom (UK) value sets based on UK time trade-off (TTO) valuation techniques and will use the Decision Support Unit (DSU) model to cross-walk to the EQ-5D-3L value set from the UK to derive a single index value. The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility. | Day 169 and End of treatment (up to approximately 232 weeks) |
| The Number of Participants Treatment-Emergent Adverse Events (TEAE) | TEAE is defined as any AEs that begin or worsen on or after the day of the first dose. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. An SAE is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or constitutes an important medical event. The severity/intensity of AEs will be graded based on the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death. | From first dose through 42 days after the last dose (up to approximately 238 weeks) |
| CL/F (L/Day) | Apparent clearance | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| V1/F (L) | Apparent volume of distribution of the central compartment | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| Ka (Day-1) | First-order rate constant of absorption | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| T1/2 (Day) | Elimination half-life | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| Tmax (Day) | Time to reach the maximum concentration for the first dose (Cmax) | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| Cmax (µg/mL) | Maximum concentration for the first dose | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| Cmax.ss (µg/mL) | Maximum concentration for the first dose (Cmax) at steady state for the starting dose | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| AUCss (Day* µg/mL) | Area under the concentration-time curve at the steady state for the starting dose | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| The Number of Participants With Antidrug Antibody (ADA) Measurements | The ADA status of a participant during treatment is determined based on the longitudinal ADA results as follows: Negative: All samples (baseline and post-baseline) are negative. Positive to treatment-emergent ADA: At least one post-baseline sample is positive if the baseline sample is negative, or at least one post-baseline sample is positive with a titer ≥ 4-fold of the baseline titer if the baseline sample is positive | C1D1 (pre- dose), C2D1, C4D1, C6D1, C8D1, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
| Mean Changes in Hemoglobin Over the Study Compared to Baseline in the Absence of RBC Transfusions (Cohorts 1 and 3A) | Calculated based on average hemoglobin measurements collected during the treatment period.The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. The baseline RBC transfusion is defined as average number of RBC units/28 days over the 84 days period immediately prior to the C1D1 date. | Baseline and Day 1 through end of treatment (up to approximately 232 weeks) |
| The Number of Participants With a Mean Hemoglobin Increase >= 1.5 g/dL From Baseline Over Any Consecutive 84-day Period (Cohorts 1 and 3A) | The number of participants with a Mean hemoglobin increase of ≥ 1.5 g/dL from baseline over any consecutive 84-day period without an RBC transfusion. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as all non-missing Hgb records within 28 days on or prior to date of first dose (or date of enrollment if not treated). | Baseline and Day 1 through end of treatment (up to approximately 232 weeks) |
| Phoenix |
| Arizona |
| 85054 |
| United States |
| Local Institution - 103 | Stanford | California | 94305 | United States |
| Stanford Cancer Center | Stanford | California | 94305 | United States |
| Local Institution - 101 | Jacksonville | Florida | 32224 | United States |
| Mayo Clinic - Jacksonville | Jacksonville | Florida | 32224 | United States |
| Local Institution - 107 | Orange City | Florida | 32763 | United States |
| Mid Florida Hematology and Oncology Centers, PA | Orange City | Florida | 32763 | United States |
| H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States |
| Local Institution - 108 | Tampa | Florida | 33612 | United States |
| Local Institution - 104 | New York | New York | 10029 | United States |
| Mount Sinai Medical Center | New York | New York | 10029 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Local Institution - 109 | Cleveland | Ohio | 44195 | United States |
| Avera Research Institute | Sioux Falls | South Dakota | 57105 | United States |
| Local Institution - 105 | Sioux Falls | South Dakota | 57105 | United States |
| Local Institution - 100 | Houston | Texas | 77030 | United States |
| MD Anderson Cancer Center The University of Texas | Houston | Texas | 77030 | United States |
| Local Institution - 106 | San Antonio | Texas | 78229 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| CHRU de Brest - Hopital Morvan | Brest | 29609 | France |
| Local Institution - 203 | Brest | 29609 | France |
| Centre Hospitalier de Lens | Lens | 62307 | France |
| Local Institution - 201 | Lens | 62307 | France |
| Hopital Saint Louis | Paris | 75010 | France |
| Local Institution - 200 | Paris | 75010 | France |
| Gustave Roussy | Villejuif | 94805 | France |
| Local Institution - 202 | Villejuif | 94805 | France |
| Azienda Ospedaliera Papa Giovanni XXIII | Bergamo | 24127 | Italy |
| Local Institution - 304 | Bergamo | 24127 | Italy |
| Azienda Ospedaliera Universitaria Careggi | Florence | 50134 | Italy |
| Local Institution - 300 | Florence | 50134 | Italy |
| Fondazione IRCCS Policlinico San Matteo | Pavia | 27100 | Italy |
| Local Institution - 301 | Pavia | 27100 | Italy |
| Istituto Clinico Humanitas | Rozzano (MI) | 20089 | Italy |
| Local Institution - 303 | Rozzano (MI) | 20089 | Italy |
| Local Institution - 302 | Varese | 21100 | Italy |
| Ospedale di Circolo di Varese | Varese | 21100 | Italy |
| Belfast Health and Social Care Trust | Belfast Northern Ireland | BT9 7AB | United Kingdom |
| Local Institution - 404 | Cardiff | CF14 4XW | United Kingdom |
| University Hospital of Wales | Cardiff | CF14 4XW | United Kingdom |
| Local Institution - 400 | Headington, Oxford | OX3 7LE | United Kingdom |
| University of Oxford | Headington, Oxford | OX3 7LE | United Kingdom |
| Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital | London | SE1 9RT | United Kingdom |
| Local Institution - 403 | London | SE1 9RT | United Kingdom |
| Imperial College London | London | W12 0HS | United Kingdom |
| Local Institution - 402 | London | W12 0HS | United Kingdom |
| BMS Clinical Trial Patient Recruiting | View source |
| FG001 | Cohort 2: RBC-Transfusion Dependent | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| FG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| FG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| COMPLETED | Treatment ongoing |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: Anemia Only | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| BG001 | Cohort 2: RBC-Transfusion Dependent | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| BG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| BG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
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| Primary | The Number of Participants With Anemia Responses Over Any 84-Day Period During the Primary Treatment Period | The number of participants that achieved anemia response as it relates to hemoglobin (Hgb) increase and red blood cell (RBC)-transfusion independence is defined below: Cohorts 1 (anemia only) and 3A: The number of participants achieving ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion from Day 1 up through and including Day 168. Cohorts 2 (RBC-transfusion dependent) and 3B: The number of participants who become RBC-transfusion free over any consecutive 84-day period from Day 1 up through and including Day 168. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose. | Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept. | Posted | Count of Participants | Participants | No | Any consecutive "rolling" 84-day period from Day 1 through and including Day 168 |
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| Secondary | Time to Anemia Response During the Primary Treatment Period | Time to anemia response follows the definitions below: Cohorts 1 (anemia only) and 3A: Time between first administration of luspatercept and the first hemoglobin increase of ≥ 1.5 g/dL from baseline that starts a consecutive 84-day period of consecutive increase ≥ 1.5 g/dL without RBC transfusions. Cohorts 2 (RBC-transfusion dependent) and 3B: Time between first administration of luspatercept and the first day of an RBC transfusion-free period of 84 days. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose. | ITT population who achieved anemia response. (Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept.) | Posted | Mean | Standard Deviation | Days | From first dose up to first onset of anemia response (calculated from Day 1 through and including Day 168) |
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| Secondary | Duration of Anemia Response | The duration of anemia response is defined as the duration of time from first day of longest response to the last day of longest response. Participants who achieved and maintained the anemia response at the time of the analysis are censored at the efficacy cutoff date. For Cohorts 1 and 3A, an anemia responder was defined as a subject with ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion. For Cohorts 2 and 3B, an anemia responder was defined as a subject who becomes RBC transfusion free over any consecutive 84-day period. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose. | ITT population who achieved anemia response. (Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept.) | Posted | Mean | Standard Deviation | Days | From first dose through last day of longest response (calculated from Day 1 through end of treatment, up to approximately 232 weeks) |
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| Secondary | The Number of RBC Units Transfused Per Participant Per 28 Days (Cohorts 2 and 3B Only) | Frequency of RBC transfusion is defined as the mean number of RBC units transfused per participant every 4 weeks (28 days). The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. | Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept. Pre-specified to be collected for Cohorts 2 and 3B only. | Posted | Mean | Standard Deviation | RBC Units | From Day 1 through end of treatment (up to approximately 232 weeks). |
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| Secondary | The Number Participants Achieving >=50% RBC Transfusion Burden Reduction From Baseline Over Any 84-Day Period (Cohorts 2 and 3B Only) | The number of participants who reduce their transfusion burden by ≥ 50% from baseline over any consecutive 84-day period. Baseline is defined as average number of RBC units per 28 days over the 84 days period on or prior to the C1D1 date. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. | Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept. Pre-specified to be collected for Cohorts 2 and 3B only. | Posted | Count of Participants | Participants | Baseline and from Day 1 through end of treatment (up to approximately 232 weeks). |
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| Secondary | The Number of Participants Who Achieve ≥ 50% Reduction in Fatigue Symptom as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | Symptoms response improvement will be assessed using the number of participants who achieve ≥ 50% reduction in fatigue symptoms. Fatigue is 1 out of 10 total symptoms scored on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as the last value on or before the first dose of study drug. Last Available = Last available assessment on or before the end of the treatment period. Mean = Mean value of the weekly assessments over the treatment period. | Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept. | Posted | Count of Participants | Participants | Baseline and from Day 1 through end of treatment (up to approximately 232 weeks) |
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| Secondary | The Number of Participants Who Achieve ≥ 50% Reduction in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) | TSS includes 10 items - worst fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers, scored on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). For participants who completed at least six of these 10 items, the MPN-SAF TSS was computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus had a possible range of 0 to 100. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as the last value on or before the first dose of study drug. Last Available = Last available assessment on or before the end of the treatment period. Mean = Mean value of the weekly assessments over the treatment period. | Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept. | Posted | Count of Participants | Participants | Baseline and from Day 1 through end of treatment (up to approximately 232 weeks) |
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| Secondary | Mean Changes in the Functional Assessment of Cancer Therapy - Anemia (FACT-An) Total Scores Over the Study Compared to Baseline | The Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire includes 47 items rating on a 5-point Likert scale from 0 (not at all) to 4 (very much) on five primary subscales:
A total score for the FACT-An can be calculated by summing the five primary subscales with a score range from 0-188. Higher scores representing better quality of life. Baseline is defined as the last value on or before the first dose of study drug. | ITT population with available health related quality of life (HRQOL) assessments. (Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept.) | Posted | Mean | Standard Deviation | Score on a scale | Day 169 and End of treatment (up to approximately 232 weeks) |
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| Secondary | Mean Change in EQ-5D-5L Utility Score Compared to Baseline | The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index for this analysis will be derived using the United Kingdom (UK) value sets based on UK time trade-off (TTO) valuation techniques and will use the Decision Support Unit (DSU) model to cross-walk to the EQ-5D-3L value set from the UK to derive a single index value. The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility. | Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept. | Posted | Mean | Standard Deviation | Score on a scale | Day 169 and End of treatment (up to approximately 232 weeks) |
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| Secondary | The Number of Participants Treatment-Emergent Adverse Events (TEAE) | TEAE is defined as any AEs that begin or worsen on or after the day of the first dose. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. An SAE is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or constitutes an important medical event. The severity/intensity of AEs will be graded based on the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death. | Safety population: All enrolled participants who received at least 1 dose of luspatercept. | Posted | Count of Participants | Participants | From first dose through 42 days after the last dose (up to approximately 238 weeks) |
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| Secondary | CL/F (L/Day) | Apparent clearance | All treated participants with available serum concentration measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter/day | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | V1/F (L) | Apparent volume of distribution of the central compartment | All treated participants with available serum concentration measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | Ka (Day-1) | First-order rate constant of absorption | All treated participants with available serum concentration measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | Day-1 | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | T1/2 (Day) | Elimination half-life | All treated participants with available serum concentration measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | Day | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | Tmax (Day) | Time to reach the maximum concentration for the first dose (Cmax) | All treated participants with available serum concentration measurements | Posted | Median | Full Range | Day | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | Cmax (µg/mL) | Maximum concentration for the first dose | All treated participants with available serum concentration measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | Cmax.ss (µg/mL) | Maximum concentration for the first dose (Cmax) at steady state for the starting dose | All treated participants with available serum concentration measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | AUCss (Day* µg/mL) | Area under the concentration-time curve at the steady state for the starting dose | All treated participants with available serum concentration measurements | Posted | Geometric Mean | Geometric Coefficient of Variation | day* µg/mL | C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | The Number of Participants With Antidrug Antibody (ADA) Measurements | The ADA status of a participant during treatment is determined based on the longitudinal ADA results as follows: Negative: All samples (baseline and post-baseline) are negative. Positive to treatment-emergent ADA: At least one post-baseline sample is positive if the baseline sample is negative, or at least one post-baseline sample is positive with a titer ≥ 4-fold of the baseline titer if the baseline sample is positive | Safety population: All enrolled participants who received at least 1 dose of luspatercept. | Posted | Count of Participants | Participants | C1D1 (pre- dose), C2D1, C4D1, C6D1, C8D1, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment. |
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| Secondary | Mean Changes in Hemoglobin Over the Study Compared to Baseline in the Absence of RBC Transfusions (Cohorts 1 and 3A) | Calculated based on average hemoglobin measurements collected during the treatment period.The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. The baseline RBC transfusion is defined as average number of RBC units/28 days over the 84 days period immediately prior to the C1D1 date. | Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept. Pre-specified to be collected for Cohorts 1 and 3A only. | Posted | Mean | Standard Deviation | g/dL | Baseline and Day 1 through end of treatment (up to approximately 232 weeks) |
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| Secondary | The Number of Participants With a Mean Hemoglobin Increase >= 1.5 g/dL From Baseline Over Any Consecutive 84-day Period (Cohorts 1 and 3A) | The number of participants with a Mean hemoglobin increase of ≥ 1.5 g/dL from baseline over any consecutive 84-day period without an RBC transfusion. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as all non-missing Hgb records within 28 days on or prior to date of first dose (or date of enrollment if not treated). | Intent-to-treat (ITT) population: All enrolled participants regardless of whether or not the participant received luspatercept. Prespecified to be reported for Cohorts 1 and 3A only. | Posted | Count of Participants | Participants | Baseline and Day 1 through end of treatment (up to approximately 232 weeks) |
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Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 4 years and 8 months) SAEs and Other AEs were assessed from first dose through 42 days after the last dose (up to approximately 238 weeks)
Not provided
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: Anemia Only | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. | 6 | 22 | 8 | 22 | 21 | 22 |
| EG001 | Cohort 2: RBC-Transfusion Dependent | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. | 12 | 21 | 8 | 21 | 19 | 21 |
| EG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. | 2 | 14 | 4 | 14 | 13 | 14 |
| EG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. | 13 | 38 | 17 | 38 | 33 | 38 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 25.0 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | 25.0 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | 25.0 | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | 25.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Diverticular perforation | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Enteritis | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Small intestinal haemorrhage | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Asthenia | General disorders | 25.0 | Systematic Assessment |
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| Fatigue | General disorders | 25.0 | Systematic Assessment |
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| Gait disturbance | General disorders | 25.0 | Systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | 25.0 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | 25.0 | Systematic Assessment |
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| Systemic inflammatory response syndrome | General disorders | 25.0 | Systematic Assessment |
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| Hepatic failure | Hepatobiliary disorders | 25.0 | Systematic Assessment |
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| Biliary tract infection | Infections and infestations | 25.0 | Systematic Assessment |
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| Cerebral toxoplasmosis | Infections and infestations | 25.0 | Systematic Assessment |
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| Diverticulitis | Infections and infestations | 25.0 | Systematic Assessment |
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| Escherichia bacteraemia | Infections and infestations | 25.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | 25.0 | Systematic Assessment |
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| Influenza | Infections and infestations | 25.0 | Systematic Assessment |
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| Kidney infection | Infections and infestations | 25.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | 25.0 | Systematic Assessment |
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| Pulmonary sepsis | Infections and infestations | 25.0 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | 25.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | 25.0 | Systematic Assessment |
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| Septic shock | Infections and infestations | 25.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | 25.0 | Systematic Assessment |
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| Urosepsis | Infections and infestations | 25.0 | Systematic Assessment |
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| Ankle fracture | Injury, poisoning and procedural complications | 25.0 | Systematic Assessment |
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| Humerus fracture | Injury, poisoning and procedural complications | 25.0 | Systematic Assessment |
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| Post procedural haemorrhage | Injury, poisoning and procedural complications | 25.0 | Systematic Assessment |
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| Subdural haematoma | Injury, poisoning and procedural complications | 25.0 | Systematic Assessment |
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| Ejection fraction decreased | Investigations | 25.0 | Systematic Assessment |
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| Troponin T increased | Investigations | 25.0 | Systematic Assessment |
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| Chest wall haematoma | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
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| Acute leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 25.0 | Systematic Assessment |
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| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 25.0 | Systematic Assessment |
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| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 25.0 | Systematic Assessment |
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| Chloroma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 25.0 | Systematic Assessment |
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| Skin squamous cell carcinoma recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 25.0 | Systematic Assessment |
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| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 25.0 | Systematic Assessment |
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| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 25.0 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | 25.0 | Systematic Assessment |
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| Disturbance in attention | Nervous system disorders | 25.0 | Systematic Assessment |
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| Haemorrhage intracranial | Nervous system disorders | 25.0 | Systematic Assessment |
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| Ischaemic stroke | Nervous system disorders | 25.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | 25.0 | Systematic Assessment |
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| Subarachnoid haemorrhage | Nervous system disorders | 25.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | 25.0 | Systematic Assessment |
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| Confusional state | Psychiatric disorders | 25.0 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | 25.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | 25.0 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | 25.0 | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
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| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
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| Aortic embolus | Vascular disorders | 25.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 25.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | 25.0 | Systematic Assessment |
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| Splenomegaly | Blood and lymphatic system disorders | 25.0 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | 25.0 | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | 25.0 | Systematic Assessment |
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| Glaucoma | Eye disorders | 25.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Mouth haemorrhage | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | 25.0 | Systematic Assessment |
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| Asthenia | General disorders | 25.0 | Systematic Assessment |
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| Chills | General disorders | 25.0 | Systematic Assessment |
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| Early satiety | General disorders | 25.0 | Systematic Assessment |
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| Fatigue | General disorders | 25.0 | Systematic Assessment |
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| Influenza like illness | General disorders | 25.0 | Systematic Assessment |
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| Injection site pain | General disorders | 25.0 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | 25.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | 25.0 | Systematic Assessment |
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| Pain | General disorders | 25.0 | Systematic Assessment |
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| Peripheral swelling | General disorders | 25.0 | Systematic Assessment |
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| Pyrexia | General disorders | 25.0 | Systematic Assessment |
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| Abscess limb | Infections and infestations | 25.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | 25.0 | Systematic Assessment |
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| Cystitis | Infections and infestations | 25.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | 25.0 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | 25.0 | Systematic Assessment |
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| Sinusitis | Infections and infestations | 25.0 | Systematic Assessment |
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| Tooth infection | Infections and infestations | 25.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | 25.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | 25.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | 25.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | 25.0 | Systematic Assessment |
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| Lower limb fracture | Injury, poisoning and procedural complications | 25.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | 25.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | 25.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | 25.0 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | 25.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | 25.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | 25.0 | Systematic Assessment |
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| Blood glucose increased | Investigations | 25.0 | Systematic Assessment |
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| Weight decreased | Investigations | 25.0 | Systematic Assessment |
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| White blood cell count increased | Investigations | 25.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | 25.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Neck mass | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | 25.0 | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | 25.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | 25.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | 25.0 | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | 25.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | 25.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | 25.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | 25.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | 25.0 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | 25.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | 25.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | 25.0 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | 25.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | 25.0 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | 25.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | 25.0 | Systematic Assessment |
| |
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | 25.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | 25.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | 25.0 | Systematic Assessment |
|
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Please email | Clinical.Trials@bms.com |
| Jul 18, 2023 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| D000740 | Anemia |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000621232 | luspatercept |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria.
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| Cohort 2: RBC-Transfusion Dependent |
Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
|
|
|
|
| Cohort 2: RBC-Transfusion Dependent |
Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG001 | Cohort 2: RBC-Transfusion Dependent | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG001 | Cohort 2: RBC-Transfusion Dependent | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG001 | Cohort 2: RBC-Transfusion Dependent | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle). The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 |
| Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) |
Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
|
| OG002 | Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
| OG003 | Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib) | Participants receive a starting dose level of luspatercept at 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle) while being on a stable dose of ruxolitinib for at least 112 days immediately prior to the enrollment date. The starting dose can be titrated (increased) during the Treatment Period to 1.33 mg/kg, up to a maximum of 1.75 mg/kg, provided that the participant meets the appropriate criteria. The participant's dose may also be delayed, reduced, or discontinued, depending on the specific criteria. |
|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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