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| ID | Type | Description | Link |
|---|---|---|---|
| 2026-525660-17-00 | EU Trial (CTIS) Number |
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The main aim of this study is to find out how well elritercept works to improve anemia in participants with myelofibrosis (MF) who are taking ruxolitinib when compared to placebo.
Other aims are to learn how elritercept improves anemia compared to placebo; to learn if elritercept reduces tiredness, improves symptoms related to MF, and helps participants do physical activities more easily. The study also aims to find out how elritercept affects the bone marrow, the spleen, and whether participants develop antibodies to the study drug.
The study will also check how safe elritercept is compared to placebo, and if elritercept stays safe over a long period of time. Participants will receive study treatment for at least 9 months (36 weeks). After this period, participants who received placebo will have the option to switch to elritercept.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Elritercept | Experimental | Participants will receive elritercept at a starting dose of 3.75 milligrams per kilogram (mg/kg) subcutaneously (SC) once every 4 weeks (Q4W) on Day 1 of each 28-day cycle for approximately 36 weeks during the double-blinded treatment period, with possible up-titration to 5.0 mg/kg from Cycle 3 Day 1 based on response and safety/tolerability. Participants may continue to receive elritercept during the extended open-label treatment period. |
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| Placebo | Placebo Comparator | Participants will receive elritercept-matching placebo with equivalent volume to elritercept SC Q4W on Day 1 of each 28-day cycle for approximately 36 weeks during the double-blinded treatment period. Eligible participants may initiate elritercept at a starting dose of 3.75 mg/kg SC Q4W on Day 1 of each 28-day cycle during the extended open-label treatment period, with possible up-titration to 5.0 mg/kg after 2 cycles, based on response and safety/tolerability. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Elritercept-matching placebo |
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| Elritercept |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants Who Are Red Blood Cell-Transfusion Independent (RBC-TI) for Any Consecutive Greater Than or Equal to (≥) 12-Week Period During the 36-Week Double-Blinded Treatment Period | RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants Who Achieve ≥50 Percent (%) Reduction in RBC Transfusion Burden From Baseline Over Any Consecutive 12-Week Period | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) | |
| Proportion of Participants Who Are RBC-TI for Any Consecutive ≥16-Week Period |
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Inclusion Criteria:
Exclusion Criteria:
Prior treatment with luspatercept, sotatercept, or other transforming growth factor beta inhibitors or activin receptor ligand traps.
Systemic treatment within 28 days before randomization with any of the following:
Initiation of new iron chelation therapy or dose adjustments to existing iron chelation therapy ≤8 weeks prior to randomization. Participants on stable doses of iron chelation therapy for ≥8 weeks are allowed.
Clinically significant anemia that is due to causes other than MF or Janus kinase (JAK) inhibitor therapy (for example, thalassemia, iron deficiency, vitamin B12 and/or folate deficiencies, autoimmune or hemolytic anemia, infections, or any active clinically significant bleeding or sequestration).
Receipt of RBC transfusion for any reason(s) other than underlying MF within 12 weeks before randomization.
Life expectancy <12 months per investigator's judgment.
Clinically significant cardiovascular disease, defined as:
Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure of ≥160 millimetres of mercury (mmHg) and/or diastolic blood pressure ≥100 mmHg despite adequate treatment.
Medical history of thromboembolic events within 6 months before screening, including history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (including proximal and distal), pulmonary or arterial embolism, arterial thrombosis, or other venous thrombosis. Participants with prior superficial thrombophlebitis are allowed.
Prior history of malignancies, other than MF. Participants who are free of other malignant disease for ≥2 years and have completed treatment, including maintenance, are allowed. Participants with a history or concurrent diagnosis of the following conditions are allowed if not requiring systemic therapy:
History of solid organ or bone marrow transplantation.
Active infection requiring intravenous antibiotics within 28 days or oral antibiotics within 7 days before randomization. Prophylactic antibiotics and/or antifungals for neutropenia are allowed.
Known positivity for Human Immunodeficiency Virus (HIV), active hepatitis B virus (HBV), or active hepatitis C virus (HCV). Participants without known history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
Body mass index ≥40 kilograms per square meter (kg/m^2).
Major surgery within 28 days before randomization.
History of allergy/anaphylaxis to recombinant proteins, investigational product, or excipients (refer to the current elritercept investigator's brochure for a list of excipients), or ruxolitinib.
Any of the following local laboratory abnormalities:
Ongoing participation in another interventional clinical trial.
Participant is unwilling or, in the opinion of the investigator, the participant is unable to comply with the requirements of the protocol.
Is a person of childbearing potential but does not agree to use at least 1 form of highly effective contraception from the time of signing the ICF until at least 60 days after the last dose of elritercept or placebo.
Participants of male birth who are fertile and who have partners of childbearing potential, who do not agree to use acceptable barrier contraception, that is, a male condom, during the entire treatment period until at least 60 days after the last dose of elritercept or placebo.
If applicable, participant with a positive serum pregnancy test during the screening period or known to be pregnant or a lactating participant who does not agree to forego breastfeeding during the entire treatment period until at least 60 days after the last dose of elritercept or placebo.
For participants in France: Persons under court protection, persons not affiliated with a social security system, and protected adults.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Takeda Contact | Contact | +1-877-825-3327 | medinfoUS@takeda.com |
| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
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| Label | URL |
|---|---|
| Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language. | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
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| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| D000740 | Anemia |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| Drug |
Elritercept, SC, injection |
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RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment.
| From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Proportion of Participants Who Are RBC-TI for Any Consecutive ≥12-Week Period With Concurrent Mean Hemoglobin (Hgb) Increase ≥1.5 Grams per Deciliter (g/dL) From Baseline | RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Proportion of Participants Who Are RBC-TI for Any Consecutive ≥24-Week Period | RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Proportion of Participants Who Are RBC-TI for Any Consecutive ≥12-Week Period With Concurrent Mean Hgb Increase of ≥1.0 g/dL and ≥2.0 g/dL From Baseline | RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Proportion of Participants Who Are RBC-TI for Any Consecutive 16- or 24-Week Period With a Concurrent Mean Hgb Increase of ≥1.0 g/dL, ≥1.5 g/dL, and ≥2.0 g/dL From Baseline | RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Maximum Duration of RBC-TI for Participants Who Achieved RBC-TI for a Consecutive ≥12 Weeks | RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Maximum Duration of RBC-TI With Concurrent Mean Hgb Increase of ≥1.5 g/dL for Participants Who Achieved Consecutive ≥12 Weeks RBC-TI With Concurrent Mean Hgb Increase of ≥1.5 g/dL | RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Time to Onset of Anemia Response | Time to onset of anemia response is defined as the duration between the date of randomization and the date participant first achieved anemia response status. Anemia response is evaluated as: achievement of RBC-TI for any consecutive ≥12-week, ≥16-week, or ≥24-week period or ≥50% reduction in red blood cell transfusion burden from baseline over any consecutive 12 weeks. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Mean Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Fatigue 7a T-Score at Week 36 | PROMIS Short Form v1.0 - Fatigue 7a is a 7-item, patient-reported measure designed to assess fatigue symptoms and impact over the past 7 days. Response options are on a 5-point scale from never (1) to always (5). Raw scores are computed by summing responses to all 7 items and then converted to a standardized T-score on a scale from 0 to 100 with a mean of 50 and SD of 10 with higher scores representing worse fatigue. T-scores can be produced using a conversion table available from the instrument developer or using response pattern scoring performed by the Health Measures Scoring Service. | Baseline, Week 36 |
| Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Fatigue Scale Score at Week 36 | EORTC QLQ-C30 is a 30-item, participant-reported multidomain questionnaire designed to assess functioning, wellbeing, and symptom experience of participants with cancer. The questionnaire's items are divided among 5 multi-item scales measuring functioning (physical, role, emotional, cognitive, and social), 3 multi-item scales measuring symptoms (fatigue, nausea/vomiting, and pain), 6 items measuring symptoms (dyspnea, insomnia, appetite loss, constipation, and diarrhea) as well as financial difficulties, and a 2-item scale measuring global health status (GHS))/quality of life (QoL). Items included in GHS/QoL scale use a 7-point response metric ranging from very poor to excellent, while other items use a 4-point response metric with categories including not at all, a little, quite a bit, and very much. Scale scores are transformed to range from 0 to 100 with higher scores indicating better functioning, GHS/QoL, or worse symptomatology. | Baseline, Week 36 |
| Proportion of Participants With Meaningful Improvement and Meaningful Deterioration in PROMIS Short Form v1.0 - Fatigue 7a T-score | PROMIS Short Form v1.0 - Fatigue 7a is a 7-item, patient-reported measure designed to assess fatigue symptoms and impact over the past 7 days. Response options are on a 5-point scale from never (1) to always (5). Raw scores are computed by summing responses to all 7 items and then converted to a standardized T-score on a scale from 0 to 100 with a mean of 50 and SD of 10 with higher scores representing worse fatigue. T-scores can be produced using a conversion table available from the instrument developer or using response pattern scoring performed by the Health Measures Scoring Service. Score cutoffs to define meaningful improvement and meaningful deterioration will be determined prior to the primary analysis based on analysis of blinded trial data in accordance with a prespecified psychometric analysis plan. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Time to Meaningful Improvement and Meaningful Deterioration in PROMIS Short Form v1.0 - Fatigue 7a T-Score From Baseline | PROMIS Short Form v1.0 - Fatigue 7a is a 7-item, patient-reported measure designed to assess fatigue symptoms and impact over the past 7 days. Response options are on a 5-point scale from never (1) to always (5). Raw scores are computed by summing responses to all 7 items and then converted to a standardized T-score on a scale from 0 to 100 with a mean of 50 and SD of 10 with higher scores representing worse fatigue. T-scores can be produced using a conversion table available from the instrument developer or using response pattern scoring performed by the Health Measures Scoring Service. Score cutoffs to define meaningful improvement and meaningful deterioration will be determined prior to the primary analysis based on analysis of blinded trial data in accordance with a prespecified psychometric analysis plan. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Proportion of Participants With Meaningful Improvement and Meaningful Deterioration in EORTC QLQ-C30 Fatigue Scale Score | EORTC QLQ-C30 is a 30-item, participant-reported multidomain questionnaire designed to assess functioning, wellbeing, and symptom experience of participant with cancer. The items are divided among 5 multi-item scales measuring functioning (physical, role, emotional, cognitive, and social), 3 multi-item scales measuring symptoms (fatigue, nausea/vomiting, pain), 6 items measuring symptoms (dyspnea, insomnia, appetite loss, constipation, diarrhea) as well as financial difficulties, and a 2-item scale measuring GHS and QoL. Items included in GHS/QoL scale use a 7-point response metric ranging from very poor to excellent, while other items use a 4-point response metric, categories including not at all, a little, quite a bit, and very much. Scale scores are transformed to range from 0 to 100 with higher scores indicating better functioning, better GHS/QoL, or worse symptomatology. Score cutoffs to define meaningful improvement/deterioration to be determined before primary analysis. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Time to Meaningful Improvement and Meaningful Deterioration in EORTC QLQ-C30 Fatigue Scale Score From Baseline | EORTC QLQ-C30 is a 30-item, participant-reported multidomain questionnaire designed to assess functioning, wellbeing, and symptom experience of participant with cancer. The items are divided among 5 multi-item scales measuring functioning (physical, role, emotional, cognitive, social), 3 multi-item scales measuring symptoms (fatigue, nausea/vomiting, pain), 6 items measuring symptoms (dyspnea, insomnia, appetite loss, constipation, diarrhea) as well as financial difficulties, and a 2-item scale measuring GHS and QoL. Items included in GHS/QoL scale use a 7-point response metric ranging from very poor to excellent, while other items use a 4-point response metric, categories including not at all, a little, quite a bit, and very much. Scale scores are transformed to range from 0 to 100 with higher scores indicating better functioning, better GHS/QoL, or worse symptomatology. Score cutoffs to define meaningful improvement/deterioration to be determined before primary analysis. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Mean Changes From Baseline in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 7-Item Total Symptom Score at Week 36 | MFSAF v4.0 is a unidimensional measure assessing 7 core MF symptoms: fatigue, night sweats, itching, abdominal discomfort, pain under ribs, early satiety, and bone pain. The questionnaire asks participants to rate each symptom at its worst during the past 7 days on a 0 to 10 numeric rating scale ranging from absent (0) to worst imaginable (10). The Total Symptom Score (TSS) is calculated as the average of the 7 individual item responses multiplied by 7, yielding a score range of 0 to 70 with higher scores representing worse symptom severity. | Baseline, Week 36 |
| Proportion of Participants Achieving Confirmed 50% Reduction in MFSAF v4.0 Total Symptom Score (TSS50) | MFSAF v4.0 is a unidimensional measure assessing 7 core MF symptoms: fatigue, night sweats, itching, abdominal discomfort, pain under ribs, early satiety, and bone pain. The questionnaire asks participants to rate each symptom at its worst during the past 7 days on a 0 to 10 numeric rating scale ranging from absent (0) to worst imaginable (10). The TSS is calculated as the average of the 7 individual item responses multiplied by 7, yielding a score range of 0 to 70 with higher scores representing worse symptom severity. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Time to Symptom Response in MFSAF TSS50 From Baseline | MFSAF v4.0 is a unidimensional measure assessing 7 core MF symptoms: fatigue, night sweats, itching, abdominal discomfort, pain under ribs, early satiety, and bone pain. The questionnaire asks participants to rate each symptom at its worst during the past 7 days on a 0 to 10 numeric rating scale ranging from absent (0) to worst imaginable (10). The TSS is calculated as the average of the 7 individual item responses multiplied by 7, yielding a score range of 0 to 70 with higher scores representing worse symptom severity. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Mean Change From Baseline EORTC QLQ-C30 Physical Functioning Scale Score at Week 36 | EORTC QLQ-C30 is a 30-item, participant-reported multidomain questionnaire designed to assess functioning, wellbeing, and symptom experience of participant with cancer. The questionnaire's items include 5 multi-item scales measuring functioning (physical, role, emotional, cognitive, and social). These items use a 4-point response metric with categories including not at all, a little, quite a bit, and very much. Scale scores are transformed to range from 0 to 100 with higher scores indicating better functioning. | Baseline, Week 36 |
| Proportion of Participants With Meaningful Improvement and Meaningful Deterioration in EORTC QLQ-C30 Physical Functioning Scale Score | EORTC QLQ-C30 is a 30-item, participant-reported multidomain questionnaire designed to assess functioning, wellbeing, and symptom experience of participant with cancer. The questionnaire's items include 5 multi-item scales measuring functioning (physical, role, emotional, cognitive, and social). These items use a 4-point response metric with categories including not at all, a little, quite a bit, and very much. Scale scores are transformed to range from 0 to 100 with higher scores indicating better functioning. Score cutoffs to define meaningful improvement and meaningful deterioration will be determined prior to the primary analysis based on analysis of blinded trial data in accordance with a prespecified psychometric analysis plan. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Time to Meaningful Improvement and Meaningful Deterioration in EORTC QLQ-C30 Physical Functioning Scale Score From Baseline | EORTC QLQ-C30 is a 30-item, participant-reported multidomain questionnaire designed to assess functioning, wellbeing, and symptom experience of participant with cancer. The questionnaire's items include 5 multi-item scales measuring functioning (physical, role, emotional, cognitive, and social). These items use a 4-point response metric with categories including not at all, a little, quite a bit, and very much. Scale scores are transformed to range from 0 to 100 with higher scores indicating better functioning. Score cutoffs to define meaningful improvement and meaningful deterioration will be determined prior to the primary analysis based on analysis of blinded trial data in accordance with a prespecified psychometric analysis plan. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Proportion of Participants With Platelet Response During the 36-Week Double-Blinded Treatment Period | Platelet response includes a mean increase of ≥30×10^9/ liter (L) from baseline, a >50% increase from baseline with a count ≥50×10^9/L, and conversion from <100 to ≥100×10^9/L, each sustained for ≥12 weeks. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Proportion of Participants Achieving Spleen Volume Reduction (SVR) From Baseline as Measured by Computed Tomography/Magnetic Resonance Imaging (CT/MRI) During the 36-Week Double-Blinded Treatment Period | Proportion of participants achieving SVR of ≥10%, ≥25%, or ≥35% will be presented for this outcome measure. | From Cycle 1 Day 1 through Week 36 (each cycle is 28 days) |
| Proportion of Participants Who Develop Accelerated Phase (AP) MF | Up to approximately 7 years |
| Time to Progression in Participants Who Develop AP MF | Up to approximately 7 years |
| Proportion of Participants Who Develop Blast Phase (BP) MF | Up to approximately 7 years |
| Time to Progression in Participants Who Develop BP MF | Up to approximately 7 years |
| Plasma Concentration-Time Data for Participants Treated With Elritercept | At multiple time points from Cycle 1 Day 1 (each cycle is 28 days) up to approximately 7 years |
| Proportion of Participants Treated With Elritercept who Have Antidrug Antibodies | At multiple time points from Cycle 1 Day 1 (each cycle is 28 days) up to approximately 7 years |
| Overall Survival (OS) | OS is defined as the time from randomization to the date of death due to any cause. | From randomization to 7 years |