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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003454-41 | EudraCT Number |
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| Name | Class |
|---|---|
| Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA | INDUSTRY |
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The study will be conducted in compliance with the International Council on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.
This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in participants with anemia due to the Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate MDS with ring sideroblasts who require red blood cell (RBC) transfusions.
Anemia is considered to be one of the most prevalent cytopenias in patients who have myelodysplastic syndromes, an umbrella term used to describe disorders relating to the ineffective production of red blood cells, white blood cells, and/or platelets. Ranging in severity from mild (asymptomatic) to severe, anemia can result in patients requiring regular red blood cell (RBC) transfusions, which can lead to further complications from iron overload. The goal of this study is to assess the safety and efficacy of luspatercept versus placebo in anemic patients who are categorized as International Prognostic Scoring System-Revised (IPSS-R) very low, low, or intermediate risk Myelodysplastic syndrome (MDS), have ring sideroblasts present, and require constant RBC transfusions. The design of the study will allow a period of initial randomization of patients into either the luspatercept or placebo arm, followed by a double-blind treatment period, and then an MDS disease assessment visit. For those patients that are determined to be experiencing clinical benefit as judged from the study Investigator by this disease assessment visit, they will be permitted to enter the double-blind Extension Phase of the study. Once patients are discontinued from study treatment, they will enter a post treatment follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental Arm - Luspatercept (ACE-536) | Experimental | Starting dose of 1.0 mg/kg subcutaneous injection every 3 weeks |
|
| Control Arm: Placebo | Placebo Comparator | Subcutaneous injection every 3 weeks |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Luspatercept | Drug |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 to Week 24 | RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders. | From Week 1 through Week 24 of study treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 24 | RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 24 weeks of treatment. | From Week 1 through Week 24 of study treatment |
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Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
Ring sideroblast ≥ 15% of erythroid precursors in bone marrow or ≥ 5% (but < 15%) if SF3B1 mutation is present.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
Prior therapy with disease modifying agents for underlying MDS disease.
Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
MDS associated with del 5q cytogenetic abnormality
Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
- iron deficiency to be determined by serum ferritin less than or equal to 15 ug/L and additional testing if clinically indicated (eg, calculated transferrin saturation [iron/total iron binding capacity less than or equal to 20%] or bone marrow aspirate stain for iron).
Prior allogeneic or autologous stem cell transplant
Known history of diagnosis of acute myeloid leukemia (AML)
Use of any of the following within 5 weeks prior to randomization:
Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed:
Major surgery within 8 weeks prior to randomization. Subjects must have completely recovered from any previous surgery prior to randomization
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| Name | Affiliation | Role |
|---|---|---|
| Rodrigo Ito, MD | Celgene | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford Cancer Center | Stanford | California | 94305 | United States | ||
| Yale University School of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30504333 | Background | Porter J. Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):361-370. doi: 10.1182/asheducation-2018.1.361. | |
| 30617198 | Background | Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7. |
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229 participants were randomized and treated.
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| ID | Title | Description |
|---|---|---|
| FG000 | Luspatercept | Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle |
| FG001 | Placebo | Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle |
| 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 | Yes | No | No | Study Protocol | May 9, 2017 | Apr 30, 2020 |
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| Other |
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| Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 48 | RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 48 weeks of treatment. | From Week 1 through Week 48 of study treatment |
| Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 Through Week 48 | RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during Week 1 through Week 48. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 48 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to Week 48 were counted as non-responders. | From Week 1 through Week 48 of study treatment |
| Change From Baseline in RBC Units Transfused Over Fixed 16-Week Period | Mean change in total number of Red Blood Cells (RBC) units transfused over a fixed 16-week period (Week 9-24 or Week 33-48) from the total number of RBC units transfused in the 16 weeks immediately on or prior to first dose of study treatment. | At Baseline (16 weeks prior to first dose of study treatment) and Weeks 9 to 24 or Weeks 33 to 48 |
| Percentage of Participants Who Achieved a Modified Hematologic Erythroid Response (mHI-E) Over Any Consecutive 56-Day Period | A modified HI-E response was defined as the percentage of participants meeting the modified HI-E per the International Working Group (IWG) sustained over 56-day consecutive period during the Treatment period. For participants with a baseline RBC transfusion burden of ≥ 4 units/8 weeks, a mHI-E was defined as a reduction in RBC transfusion of at least 4 units/8 weeks; for participants with baseline RBC transfusion burden of <4 units/8 weeks, mHI-E, was defined as a mean increase in hemoglobin of ≥ 1.5 g/dL for 8 weeks in the absence of RBC transfusions. | Week 1 through 24 or Week 1 Through Week 48 |
| Percentage of Participants Who Achieved a Mean Hemoglobin (Hgb) Increase of at Least 1.0 g/dL Over Any Consecutive 56-Day Period in Absence of Red Blood Cells (RBC) Transfusions | A mean hgb increase of ≥ 1.0 g/dL was analyzed as the percentage of participants with a hgb increase ≥ 1.0 g/dL compared with baseline (after applying the 14/3 day rule) that was sustained over any consecutive 56-day (8-week) period in the absence of RBC transfusions during the treatment period. (Week 1 through Week 24 and Week 1 through Week 48). | Week 1 though Week 24 and Week 1 through 48 |
| Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24 | Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 24. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method. | From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks |
| Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48 | Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 48. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method. | From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks |
| Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Score | The EORTC questionnaire is a validated health-related quality of life (HRQoL) measure applicable to participants with any cancer diagnosis. Version 3.0 of the questionnaire was used in the study. It is composed of 30 items that address 15 domains, including one global health status, functional domains, and symptom domains. Domain scores are transformed to a 0 to 100 scale, where higher scores on the global quality of life score indicate better function. As such, a positive change from Baseline score indicates an improvement in quality of life. | Baseline and Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, every other cycle during extension phase (C1 D1, C3 D1, C5 D1, etc. up to C59 D1) and end of treatment. Each cycle is composed of 21 days. |
| Percentage of Participants Who Achieved a Hematologic Improvement in Neutrophil Response (HI-N) Over Any Consecutive 56-day Period | Percentage of participants who achieved a hematologic improvement in neutrophil response (HI-N) per IWG criteria sustained over any consecutive 56-day (8-week) period, during the treatment period (Week 1 to Week 24 and Week 1 to Week 48) HI-N was defined as at least a 100% increase and an absolute increase > 0.5 X 10^9/L. | Week 1 through Week 24 or Week 1 Through Week 48 of study treatment |
| Percentage of Participants Who Achieved a Hematologic Improvement in Platelet Response (HI-P) Over Any Consecutive 56-day Period | Percentage of participants who achieved a hematologic improvement platelet response (HI-P) was defined as the percentage of participants meeting the HI-P criteria per the IWG sustained over any consecutive 56-day (8-week) period (Week 1 to Week 24 and Week 1 to Week 48) during the treatment period. HI - P reponse was defined as:
| Week 1 through Week 24 or Week 1 Through Week 48 of study treatment |
| Change From Baseline in Mean Serum Ferritin | Mean change from baseline in mean serum ferritin was calculated as the difference of postbaseline mean serum ferritin (averaged over the specified timepoints) and baseline mean serum ferritin. | Baseline and Week 9 through Week 24 and Week 33 through Week 48 |
| Change From Baseline in Mean Daily Dose of Iron Chelation Therapy (ICT) | Mean change from baseline in mean daily dose of ICT averaged over Week 9 to Week 24 or Week 33 to Week 48. For each participant, the mean change in daily dose of ICT was calculated as the difference of postbaseline mean daily dose and baseline mean daily dose. | Baseline and Week 9 through Week 24 and Week 33 through Week 48 of study treatment |
| Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24 | Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 24 | From first dose to Week 24 of study treatment |
| Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48 | Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 48 | From first dose to Week 48 of study treatment |
| Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML) | Percentage of participants progressing to AML throughout the course of the study | From randomization to study completion (up to approximately 57 months) |
| Time to Acute Myeloid Leukemia (AML) Progression | Time to AML progression was defined as the time between randomization date and the first diagnosis of AML as per World Health Organization (WHO) classification of ≥ 20% blasts in peripheral blood or bone marrow. Participants with a diagnosis of AML were considered to have had an event, participants who did not progress to AML at the time of analysis were censored at the last assessment date which did not indicate progression to AML. | From randomization to study completion (up to approximately 57 months) |
| Overall Survival | Overall Survival was defined as the time from the date of study drug randomization to death due to any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for those who discontinued from the study or were lost to follow-up. | From randomization to study completion (up to approximately 57 months) |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | The outcome measure describes the number of participants who experienced different types of Treatment-emergent adverse events (TEAEs). TEAEs were defined as Adverse Events (AEs) that started on or after the day of the first dose and on or before 42 days after the last dose of IP. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. | From date of first dose up to 42 days after the last dose (up to approximately 83 weeks) |
| Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F) | Apparent total plasma clearance was calculated as Dose/Area Under the Curve to infinity (ꝏ). | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
| Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F) | Apparent volume of distribution of luspatercept was calculated according to the equation Vz = (CL)/λ. | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
| Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2) | Terminal phase half-life was calculated according to the following equation: t1/2 = 0.693/λz. | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
| Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax) | Tmax was defined as the observed time to maximum plasma concentration of luspatercept. | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
| Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the First Dose (Cmax) | Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration versus time. | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
| Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax) at Steady State | Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration at a steady state. | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
| Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Area Under the Curve at Steady State for Starting Dose (AUC^ss) | Area under the curve steady state was defined as the area under the plasma concentration-time curve for a steady state. calculated by the linear trapezoidal rule. | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
| Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA) | Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as "treatment-emergent" if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as "preexisting" if the baseline sample was ADA positive and the participant was not qualified for "treatment-emergent." | From randomization to 1 year post first dose |
| New Haven |
| Connecticut |
| 06510 |
| United States |
| H Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States |
| Emory University Hospital | Atlanta | Georgia | 30322 | United States |
| Ochsner Medical Institutions | New Orleans | Louisiana | 70123 | United States |
| Johns Hopkins Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | 21287 | United States |
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Columbia-Presbyterian Medical Center | New York | New York | 10032 | United States |
| Montefiore Medical Center Albert Einstein Cancer Center | The Bronx | New York | 10467 | United States |
| Gabrail Cancer Center | Canton | Ohio | 44718 | United States |
| Cleveland Clinic Taussig Cancer Institute | Cleveland | Ohio | 44195-0001 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Algemeen Ziekenhuis Klina | Brasschaat | 2930 | Belgium |
| AZ Sint-Jan AV Brugge | Bruges | 8000 | Belgium |
| UZ Brussels | Brussels | 1090 | Belgium |
| Grand Hopital de Charleroi | Charleroi | 6000 | Belgium |
| UZ Gent | Ghent | 9000 | Belgium |
| UZ Leuven | Leuven | 3000 | Belgium |
| Cliniques Universitaires UCL de Mont-Godine | Yvoir | 5530 | Belgium |
| Tom Baker Cancer Center | Calgary | Alberta | T2N 4N2 | Canada |
| Juravinski Cancer Centre | Hamilton | Ontario | L8V 1C3 | Canada |
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| CHU d'Angers | Angers | 49033 | France |
| CHU Hotel | Grenoble | 38043 | France |
| CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang | Lille | 59037 | France |
| Institut Paoli Calmettes | Marseille | 13273 | France |
| CHU de Nice Archet I | Nice | 06202 | France |
| Hopital Saint Louis | Paris | 75010 | France |
| Hopital Haut Leveque | Pessac | 33604 | France |
| Centre hospitalier Lyon Sud Hematologie | Pierre-Bénite | 69495 | France |
| Hopital civil | Strasbourg | 67091 | France |
| Institut Universitaire du Cancer de Toulouse - Oncopole | Toulouse | 31059 | France |
| Hopital Bretonneau | Tours | 37044 | France |
| Universitatsklinikum Bonn | Bonn | 53105 | Germany |
| Universitatsklinikum Carl Gustav Carus an der TU Dresden | Dresden | 01307 | Germany |
| Universitätsklinikum Düsseldorf | Düsseldorf | 40225 | Germany |
| Marien Hospital | Düsseldorf | 40479 | Germany |
| Medizinische Hochschule Hannover | Hanover | 30625 | Germany |
| Klinikum rechts der Isar der Technischen Universität München | München | 81675 | Germany |
| Azienda Ospedaliera Santi Antonio Biagio E Cesare Arrigo | Allessandria | 15100 | Italy |
| Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi | Bologna | 40138 | Italy |
| Azienda Ospedaliera Universitaria Careggi | Florence | 50121 | Italy |
| Azienda Sanitaria Locale Lecce | Lecce | 73100 | Italy |
| Fondazione IRCCS Policlinico San Matteo | Pavia | 27100 | Italy |
| Azienda Ospedaliera Bianchi Melacrino Morelli | Reggio Calabria | 89100 | Italy |
| Fondazione Policlinico Universitario A Gemelli | Roma | 00168 | Italy |
| Fondazione PTV Policlinico Tor Vergata | Roma | 00168 | Italy |
| VU Medisch Centrum | Amsterdam | 1081 HV | Netherlands |
| Universitair Medisch Centrum Groningen | Groningen | 9713 GZ | Netherlands |
| Spaarne Ziekenhuis | Hoofddorp | 2135 | Netherlands |
| Hospital Universitario Cruces | Barakaldo | 48903 | Spain |
| Hospital Universitario Vall D hebron | Barcelona | 08035 | Spain |
| Instituto Catalan de Oncologia-Hospital Duran i Reynals | Barcelona | 08908 | Spain |
| Hospital General Universitario Gregorio Marañon | Madrid | 28007 | Spain |
| Hospital Universitario Central de Asturias | Oviedo | 33011 | Spain |
| Hospital Universitario de Salamanca | Salamanca | 37007 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Hospital Universitario La Fe | Valencia | 46026 | Spain |
| Sahlgrenska Universitetssjukhus | Gothenburg | SE-41685 | Sweden |
| Skanes Universitetssjukhus Lund | Lund | 222 41 | Sweden |
| Karolinska University Hospital | Stockholm | SE-17176 | Sweden |
| Akademiska Sjukhuset | Uppsala | 75185 | Sweden |
| Cukurova University Medical Faculty Balcali Hospital | Adana | 01330 | Turkey (Türkiye) |
| Ankara University Medical Faculty Cebeci Hospital | Ankara | 06590 | Turkey (Türkiye) |
| Istanbul University Cerrahpasa Medical Faculty Hospital | Istanbul | 34098 | Turkey (Türkiye) |
| Ege Universitesi Tip Fakultesi Hastanesi | Izmir | 35100 | Turkey (Türkiye) |
| Aberdeen Royal Infirmary | Aberdeen | AB25 2ZN | United Kingdom |
| John Radcliffe Hospital | Headington | OX3 9DU | United Kingdom |
| St James University Hospital | Leeds | LS1 3EX | United Kingdom |
| Guys Hospital | London | SE1 9RT | United Kingdom |
| Kings College Hospital | London | SE5 9RS | United Kingdom |
| Kings Mill Hospital | Sutton in Ashfield | NG17 4SL | United Kingdom |
| 31914241 | Result | Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Diez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Gotze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellstrom-Lindberg E, Zeidan AM, Ades L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892. |
| 32089218 | Result | Komrokji RS. Luspatercept in Myelodysplastic Syndromes: Who and When? Hematol Oncol Clin North Am. 2020 Apr;34(2):393-400. doi: 10.1016/j.hoc.2019.10.004. Epub 2020 Jan 21. |
| 30602619 | Result | Fenaux P, Kiladjian JJ, Platzbecker U. Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis. Blood. 2019 Feb 21;133(8):790-794. doi: 10.1182/blood-2018-11-876888. Epub 2019 Jan 2. |
| 36635381 | Derived | Germing U, Fenaux P, Platzbecker U, Buckstein R, Santini V, Diez-Campelo M, Yucel A, Tang D, Fabre S, Zhang G, Zoffoli R, Ha X, Miteva D, Hughes C, Komrokji RS, Zeidan AM, Garcia-Manero G. Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study. Ann Hematol. 2023 Feb;102(2):311-321. doi: 10.1007/s00277-022-05071-8. Epub 2023 Jan 13. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Luspatercept | Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle |
| BG001 | Placebo | Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle |
| BG002 | 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 | ||||||||||
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| 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/Ethnicity, Customized | 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 | Percentage Of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 to Week 24 | RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders. | All treated participants | Posted | Number | 95% Confidence Interval | Percent of Participants | From Week 1 through Week 24 of study treatment |
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| Secondary | Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 24 | RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 24 weeks of treatment. | All treated participants | Posted | Number | 95% Confidence Interval | Percent of Participants | From Week 1 through Week 24 of study treatment |
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| Secondary | Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 48 | RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 48 weeks of treatment. | All treated participants | Posted | Number | 95% Confidence Interval | Percent of Participants | From Week 1 through Week 48 of study treatment |
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| Secondary | Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 Through Week 48 | RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during Week 1 through Week 48. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 48 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to Week 48 were counted as non-responders. | All treated participants | Posted | Number | 95% Confidence Interval | Percentage of Participants | From Week 1 through Week 48 of study treatment |
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| Secondary | Change From Baseline in RBC Units Transfused Over Fixed 16-Week Period | Mean change in total number of Red Blood Cells (RBC) units transfused over a fixed 16-week period (Week 9-24 or Week 33-48) from the total number of RBC units transfused in the 16 weeks immediately on or prior to first dose of study treatment. | All treated participants with available measurements at the indicated timepoints | Posted | Mean | Standard Deviation | Units | At Baseline (16 weeks prior to first dose of study treatment) and Weeks 9 to 24 or Weeks 33 to 48 |
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| Secondary | Percentage of Participants Who Achieved a Modified Hematologic Erythroid Response (mHI-E) Over Any Consecutive 56-Day Period | A modified HI-E response was defined as the percentage of participants meeting the modified HI-E per the International Working Group (IWG) sustained over 56-day consecutive period during the Treatment period. For participants with a baseline RBC transfusion burden of ≥ 4 units/8 weeks, a mHI-E was defined as a reduction in RBC transfusion of at least 4 units/8 weeks; for participants with baseline RBC transfusion burden of <4 units/8 weeks, mHI-E, was defined as a mean increase in hemoglobin of ≥ 1.5 g/dL for 8 weeks in the absence of RBC transfusions. | All treated participants | Posted | Number | 95% Confidence Interval | Percentage of Participants | Week 1 through 24 or Week 1 Through Week 48 |
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| Secondary | Percentage of Participants Who Achieved a Mean Hemoglobin (Hgb) Increase of at Least 1.0 g/dL Over Any Consecutive 56-Day Period in Absence of Red Blood Cells (RBC) Transfusions | A mean hgb increase of ≥ 1.0 g/dL was analyzed as the percentage of participants with a hgb increase ≥ 1.0 g/dL compared with baseline (after applying the 14/3 day rule) that was sustained over any consecutive 56-day (8-week) period in the absence of RBC transfusions during the treatment period. (Week 1 through Week 24 and Week 1 through Week 48). | All treated participants | Posted | Number | 95% Confidence Interval | Percentage of Participants | Week 1 though Week 24 and Week 1 through 48 |
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| Secondary | Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24 | Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 24. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method. | All treated participants who achieved RBC-TI ≥ 8 weeks during Week 1 through Week 24 of study treatment | Posted | Median | 95% Confidence Interval | Weeks | From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks |
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| Secondary | Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48 | Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 48. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method. | All treated participants who achieved RBC-TI ≥ 8 weeks during Week 1 through Week 48 of study treatment | Posted | Median | 95% Confidence Interval | Weeks | From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks |
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| Secondary | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Score | The EORTC questionnaire is a validated health-related quality of life (HRQoL) measure applicable to participants with any cancer diagnosis. Version 3.0 of the questionnaire was used in the study. It is composed of 30 items that address 15 domains, including one global health status, functional domains, and symptom domains. Domain scores are transformed to a 0 to 100 scale, where higher scores on the global quality of life score indicate better function. As such, a positive change from Baseline score indicates an improvement in quality of life. | All treated participants who completed the EORTC QLQ-C30 assessment at baseline and at least one post-baseline assessment visit. | Posted | Mean | Standard Deviation | Score on a scale | Baseline and Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, every other cycle during extension phase (C1 D1, C3 D1, C5 D1, etc. up to C59 D1) and end of treatment. Each cycle is composed of 21 days. |
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| Secondary | Percentage of Participants Who Achieved a Hematologic Improvement in Neutrophil Response (HI-N) Over Any Consecutive 56-day Period | Percentage of participants who achieved a hematologic improvement in neutrophil response (HI-N) per IWG criteria sustained over any consecutive 56-day (8-week) period, during the treatment period (Week 1 to Week 24 and Week 1 to Week 48) HI-N was defined as at least a 100% increase and an absolute increase > 0.5 X 10^9/L. | All treated participants with available measurements | Posted | Number | 95% Confidence Interval | Percentage of Participants | Week 1 through Week 24 or Week 1 Through Week 48 of study treatment |
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| Secondary | Percentage of Participants Who Achieved a Hematologic Improvement in Platelet Response (HI-P) Over Any Consecutive 56-day Period | Percentage of participants who achieved a hematologic improvement platelet response (HI-P) was defined as the percentage of participants meeting the HI-P criteria per the IWG sustained over any consecutive 56-day (8-week) period (Week 1 to Week 24 and Week 1 to Week 48) during the treatment period. HI - P reponse was defined as:
| All treated participants with available measurements | Posted | Number | 95% Confidence Interval | Percentage of Participants | Week 1 through Week 24 or Week 1 Through Week 48 of study treatment |
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| Secondary | Change From Baseline in Mean Serum Ferritin | Mean change from baseline in mean serum ferritin was calculated as the difference of postbaseline mean serum ferritin (averaged over the specified timepoints) and baseline mean serum ferritin. | All treated participants with available measurements | Posted | Least Squares Mean | Standard Error | ug/L | Baseline and Week 9 through Week 24 and Week 33 through Week 48 |
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| Secondary | Change From Baseline in Mean Daily Dose of Iron Chelation Therapy (ICT) | Mean change from baseline in mean daily dose of ICT averaged over Week 9 to Week 24 or Week 33 to Week 48. For each participant, the mean change in daily dose of ICT was calculated as the difference of postbaseline mean daily dose and baseline mean daily dose. | All treated participants with available measurements | Posted | Least Squares Mean | Standard Error | mg/day | Baseline and Week 9 through Week 24 and Week 33 through Week 48 of study treatment |
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| Secondary | Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24 | Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 24 | All participants who achieved RBC-TI ≥ 8 weeks during Week 1 through Week 24 | Posted | Mean | Standard Deviation | Days | From first dose to Week 24 of study treatment |
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| Secondary | Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48 | Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 48 | All participants who achieved RBC-TI ≥ 8 weeks during Week 1 through Week 48 | Posted | Mean | Standard Deviation | Days | From first dose to Week 48 of study treatment |
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| Secondary | Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML) | Percentage of participants progressing to AML throughout the course of the study | All treated participants | Posted | Number | Percentage of Participants | From randomization to study completion (up to approximately 57 months) |
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| Secondary | Time to Acute Myeloid Leukemia (AML) Progression | Time to AML progression was defined as the time between randomization date and the first diagnosis of AML as per World Health Organization (WHO) classification of ≥ 20% blasts in peripheral blood or bone marrow. Participants with a diagnosis of AML were considered to have had an event, participants who did not progress to AML at the time of analysis were censored at the last assessment date which did not indicate progression to AML. | All treated participants who progressed to AML | Posted | Median | 95% Confidence Interval | Months | From randomization to study completion (up to approximately 57 months) |
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| Secondary | Overall Survival | Overall Survival was defined as the time from the date of study drug randomization to death due to any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for those who discontinued from the study or were lost to follow-up. | All treated participants | Posted | Median | 95% Confidence Interval | Months | From randomization to study completion (up to approximately 57 months) |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | The outcome measure describes the number of participants who experienced different types of Treatment-emergent adverse events (TEAEs). TEAEs were defined as Adverse Events (AEs) that started on or after the day of the first dose and on or before 42 days after the last dose of IP. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. | All treated participants | Posted | Count of Participants | Participants | From date of first dose up to 42 days after the last dose (up to approximately 83 weeks) |
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| Secondary | Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F) | Apparent total plasma clearance was calculated as Dose/Area Under the Curve to infinity (ꝏ). | Pharmacokinetic (PK) population included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/day | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
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| Secondary | Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F) | Apparent volume of distribution of luspatercept was calculated according to the equation Vz = (CL)/λ. | Pharmacokinetic population included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
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| Secondary | Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2) | Terminal phase half-life was calculated according to the following equation: t1/2 = 0.693/λz. | Pharmacokinetic population Included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | Day | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
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| Secondary | Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax) | Tmax was defined as the observed time to maximum plasma concentration of luspatercept. | Pharmacokinetic population Included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations. | Posted | Median | Full Range | Day | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
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| Secondary | Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the First Dose (Cmax) | Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration versus time. | Pharmacokinetic population Included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
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| Secondary | Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax) at Steady State | Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration at a steady state. | Pharmacokinetic population included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
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| Secondary | Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Area Under the Curve at Steady State for Starting Dose (AUC^ss) | Area under the curve steady state was defined as the area under the plasma concentration-time curve for a steady state. calculated by the linear trapezoidal rule. | Pharmacokinetic population included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | day/μg/mL | Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter. |
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| Secondary | Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA) | Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as "treatment-emergent" if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as "preexisting" if the baseline sample was ADA positive and the participant was not qualified for "treatment-emergent." | Safety population of participants with ADA samples collected. | Posted | Count of Participants | Participants | From randomization to 1 year post first dose |
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All-cause mortality was assessed from first dose to study completion (up to approximately 57 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 91 weeks)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Luspatercept | Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle | 45 | 153 | 66 | 153 | 145 | 153 |
| EG001 | Placebo | Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle | 24 | 76 | 23 | 76 | 63 | 76 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Aortic valve stenosis | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Arteriosclerosis coronary artery | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Atrioventricular block | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Atrioventricular block second degree | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Bradycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Cardiac failure acute | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Supraventricular tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Duodenal ulcer | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Pancreatitis acute | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Death | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Gait disturbance | General disorders | MedDRA 23.0 | Systematic Assessment |
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| General physical health deterioration | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Generalised oedema | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
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| Abdominal infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Diverticulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Epididymitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Localised infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Metapneumovirus infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Orchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Parainfluenzae virus infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Pneumonia moraxella | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia staphylococcal | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Septic shock | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Urinary tract infection bacterial | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Joint injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Pelvic bone injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Spinal column injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| General physical condition abnormal | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Chondritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Gouty arthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Muscle haemorrhage | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Myositis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Polymyalgia rheumatica | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Colon adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Intraductal papillary mucinous neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Refractory anaemia with an excess of blasts | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Systemic mastocytosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Transformation to acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cerebrospinal fluid leakage | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Thrombosis in device | Product Issues | MedDRA 23.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Urethral stenosis | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Aortic stenosis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Granulomatosis with polyangiitis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Shock haemorrhagic | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Iron overload | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.0 | 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 |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 31, 2018 | May 1, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D000740 | Anemia |
| ID | Term |
|---|---|
| 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 |
|
| White |
|
| Not Collected or Reported |
|
| Other |
|
| Odds Ratio (OR) |
| 5.065 |
| 2-Sided |
| 95 |
| 2.278 |
| 11.259 |
| Superiority |
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