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A Study of IMR-687 in Subjects With Beta Thalassemia

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
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
Last Update Posted : May 13, 2022
Sponsor:
Information provided by (Responsible Party):
Imara, Inc.

Study Description
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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

Detailed Description:
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 Design
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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 related topics: Thalassemia

Arms and Interventions
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Arm Intervention/treatment
Experimental: Lower Dose IMR-687
Oral administration of once daily IMR-687
 Drug: IMR-687
Oral administration of once daily IMR-687
Experimental: Higher dose IMR-687
Oral administration of once daily IMR-687
 Drug: IMR-687
Oral administration of once daily IMR-687
Placebo Comparator: Placebo
Oral administration of once daily placebo
 Drug: Placebo
Oral administration of once daily Placebo


Outcome Measures
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Primary Outcome Measures :
  1. IMR-687 Safety and tolerability [ Time Frame: Baseline to Week 40 ]
    1. Incidence and severity of Adverse Events
    2. Incidence and severity of Serious Adverse Events


Secondary Outcome Measures :
  1. TDT Patients: Reduction in red blood cell (RBC) transfusion burden [ Time Frame: Week 12 to Week 36 ]
    1. Proportion of patients with ≥20% hematological improvement (as measured by reduced transfusion burden) from Week 12 to Week 24, Week 24 to Week 36, and Week 12 to Week 36, compared to the 12 weeks prior to Baseline (Day 1).
    2. Proportion of patients with ≥33% hematological improvement (as measured by reduced transfusion burden) from Week 12 to Week 24, Week 24 to Week 36, and Week 12 to Week 36, compared to the 12 week prior to Baseline (Day 1)

  2. TDT Patients: Mean number of transfusion events [ Time Frame: Baseline to Week 36 ]
    a. Mean number of transfusion events

  3. TDT and NTDT Patients: Mean change in ICT dose and Serum ferritin levels [ Time Frame: Baseline to Week 36 ]
    a. Mean change in ICT daily dose and serum ferritin levels

  4. NTDT Patients: Change in Hb [ Time Frame: Baseline to Week 36 ]
    1. Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 12 to Week 24 and Week 24 to Week 36 in the absence of transfusions.
    2. Mean change from baseline in mean Hb values at Week 12 to Week 24 and Week 24 to Week 36 in the absence of transfusions.

  5. NTDT Patients: Mean change in HbF [ Time Frame: Baseline to Week 36 ]
    1. Mean change from baseline in mean HbF values at Week 12 to Week 24 and Week 24 to Week 36 in the absence of transfusions.
    2. Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 and Week 24 to Week 36 in absence of transfusions.

  6. TDT and NTDT Patients: PK Parameter Cmax [ Time Frame: Baseline to Week 36 ]
    a. Peak Plasma Concentration (Cmax)

  7. TDT and NTDT Patients: PK Parameter AUC 0-24 [ Time Frame: Baseline to Week 36 ]
    a. Area Under the Plasma Concentration versus Time Curve (AUC) from time 0 to 24 hours


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  1. Documented diagnosis of β-thalassemia or HbE/ β-thalassemia in their medical history. Concomitant alpha gene deletion, duplication, or triplication is allowed.
  2. 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. .
  3. Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.
  4. 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.
  5. 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
  6. hematopoietic stem cell transplantation within 9 months.
  7. 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.
  8. ECOG performance score of 0 to 1
  9. 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:

  1. Diagnosis of α-thalassemia (e.g., hemoglobin H [HbH]) or hemoglobin S (HbS)/ β thalassemia.
  2. Body mass index (BMI) <17.0 kg/m2 or a total body weight <45 kg; or BMI >35 kg/m2
  3. 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).
  4. Stroke requiring medical intervention ≤24 weeks prior to randomization.
  5. Platelet count >1000 × 109/L.
  6. 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.
  7. 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.
  8. Prior exposure to sotatercept or luspatercept, IMR-687, or gene therapy within 6 months prior to randomization (Day 1).
  9. Subjects who have major organ damage
Contacts and Locations
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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
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Sponsors and Collaborators
Imara, Inc.
Investigators
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Study Director: Kenneth Attie, MD Imara, Inc.
More Information
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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
Last Update Posted: May 13, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imara, Inc.:
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