A Study of IMR-687 in Subjects With Beta Thalassemia
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04411082 |
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Recruitment Status :
Terminated
(IMR-BTL-201demonstrated that while IMR-687 was generally well-tolerated, it failed to show any meaningful benefit in transfusion burden or improvement in most disease-related biomarkers. So, the sponsor has decided to discontinue this study)
First Posted : June 2, 2020
Results First Posted : June 30, 2022
Last Update Posted : June 30, 2022
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Sponsor:
Imara, Inc.
Information provided by (Responsible Party):
Imara, Inc.
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Brief Summary:
A Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| β Thalassemia | Drug: IMR-687 Drug: Placebo | Phase 2 |
A phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of IMR-687 (phosphodiesterase (PDE) 9 inhibitor) administered once daily (qd) orally for 36 weeks in 2 populations of adult subjects with β-thalassemia: Population 1 (Transfusion Dependent Thalassemia (TDT) subjects) and Population 2 (Non-Transfusion Dependent Thalassemia (NTDT) subjects).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 122 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Masking Description: | Double-Blind |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2 Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects With Beta Thalassemia |
| Actual Study Start Date : | October 16, 2020 |
| Actual Primary Completion Date : | March 11, 2022 |
| Actual Study Completion Date : | May 4, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Beta thalassemia
MedlinePlus related topics:
Thalassemia
| Arm | Intervention/treatment |
|---|---|
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Experimental: Lower Dose IMR-687
Oral administration of once daily IMR-687
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Drug: IMR-687
Oral administration of once daily IMR-687 |
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Experimental: Higher dose IMR-687
Oral administration of once daily IMR-687
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Drug: IMR-687
Oral administration of once daily IMR-687 |
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Placebo Comparator: Placebo
Oral administration of once daily placebo
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Drug: Placebo
Oral administration of once daily Placebo |
Primary Outcome Measures :
- IMR-687 Safety and Tolerability [ Time Frame: Baseline to Week 40 ]Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events
Secondary Outcome Measures :
- TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24 [ Time Frame: Baseline to Week 24 ]Proportion of patients with ≥33% hematological improvement (as measured by reduced transfusion burden) from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)
- NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions. [ Time Frame: Baseline to Week 24 ]Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 12 to Week 24 in the absence of transfusions.
- NTDT Patients: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 12 to Week 24 in Absence of Transfusions [ Time Frame: Baseline to Week 24 ]Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions
- TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36 [ Time Frame: Baseline to Week 36 ]Proportion of patients with ≥33% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)
- TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24 [ Time Frame: Baseline to Week 24 ]Proportion of patients with ≥50% hematological improvement from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)
- TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36 [ Time Frame: Baseline to Week 36 ]Proportion of patients with ≥50% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)
- NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions [ Time Frame: Baseline to Week 36 ]Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 24 to Week 36 in the absence of transfusions.
- NTDT: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 24 to Week 36 in Absence of Transfusions [ Time Frame: Baseline to Week 36 ]Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Documented diagnosis of β-thalassemia or HbE/ β-thalassemia in their medical history. Concomitant alpha gene deletion, duplication, or triplication is allowed.
- Documentation of the dates of transfusion events and the number of all pRBC units per event within the 12 weeks prior to the Baseline (Day 1) visit. .
- Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.
- TDT Subjects: subjects must be regularly transfused, defined as >3 to 10 pRBC units in the12 weeks prior to Baseline (Day 1) visit and no transfusion-free period for >35 days during that period.
- NTDT subjects: Subjects must be transfusion independent, defined as 0 to ≤3 units of pRBCs received during the 12-week period prior to the Baseline (Day 1) visit, must not be on a regular transfusion program, must be RBC transfusion-free for at least ≥ 4 weeks prior to randomization, and must not be scheduled to start a regular
- hematopoietic stem cell transplantation within 9 months.
- NTDT subjects: Subjects must have Hb ≤10.0 g/dL at Screening; the screening Hb sample must be collected 7 to 28 days prior to randomization. Hb values within 21 days post-transfusion will be excluded.
- ECOG performance score of 0 to 1
- Female subjects must not be pregnant, or breastfeeding and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner.
Exclusion Criteria:
- Diagnosis of α-thalassemia (e.g., hemoglobin H [HbH]) or hemoglobin S (HbS)/ β thalassemia.
- Body mass index (BMI) <17.0 kg/m2 or a total body weight <45 kg; or BMI >35 kg/m2
- Subjects with known active hepatitis A, hepatitis B, or hepatitis C, with active or acute event of malaria, or who are known to be positive for human immunodeficiency virus (HIV).
- Stroke requiring medical intervention ≤24 weeks prior to randomization.
- Platelet count >1000 × 109/L.
- Participated in another clinical study of an investigational agent (or device) within 30 days or 5-half-lives of date of informed consent, whichever is longer, or is currently participating in another study.
- For Subjects on iron chelation therapy (ICT) at the time of ICF signing, initiation of ICT less than 24 weeks before the predicted randomization date.
- Prior exposure to sotatercept or luspatercept, IMR-687, or gene therapy within 6 months prior to randomization (Day 1).
- Subjects who have major organ damage
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04411082
Locations
Show 36 study locations
Sponsors and Collaborators
Imara, Inc.
Investigators
| Study Director: | Kenneth Attie, MD | Imara, Inc. |
Study Documents (Full-Text)
Documents provided by Imara, Inc.:
Documents provided by Imara, Inc.:
Study Protocol [PDF] March 15, 2021
Statistical Analysis Plan [PDF] October 14, 2021
| Responsible Party: | Imara, Inc. |
| ClinicalTrials.gov Identifier: | NCT04411082 |
| Other Study ID Numbers: |
IMR-BTL-201 2019-002989-12 ( EudraCT Number ) |
| First Posted: | June 2, 2020 Key Record Dates |
| Results First Posted: | June 30, 2022 |
| Last Update Posted: | June 30, 2022 |
| Last Verified: | June 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Imara, Inc.:
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Transfusion TDT NTDT |
Additional relevant MeSH terms:
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Thalassemia beta-Thalassemia Anemia, Hemolytic, Congenital Anemia, Hemolytic |
Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |