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A Study of IMR-687 in Subjects With Beta Thalassemia

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ClinicalTrials.gov Identifier: NCT04411082
Recruitment Status : Recruiting
First Posted : June 2, 2020
Last Update Posted : October 23, 2020
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) 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)
Estimated Enrollment : 120 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
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 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. Proportion of patients with adverse events and serious adverse events [ Time Frame: Baseline to Week 40 ]
    1. Incidence of Adverse Events
    2. Incidence of Serious Adverse Events


Secondary Outcome Measures :
  1. TDT Patients: Reduction in red blood cell (RBC) transfusion burden [ Time Frame: Week 12 through Week 36 ]
    1. Proportion of patients with ≥20% hematological improvement as compared to the 12 week prescreening timeframe
    2. Proportion of patients with ≥33% hematological improvement as compared to the 12 week prescreening timeframe

  2. TDT Patients: Mean number of transfusion events [ Time Frame: Baseline to Week 36, Weeks 24 to 36 ]
    a. Mean number of transfusion events

  3. TDT Patients: Mean change in ICT dose and Serum ferritin levels [ Time Frame: Baseline to Week 36, Weeks 24 to 36 ]
    a. Mean change in ICT dose and Serum ferritin levels

  4. TDT Patients: Proportion of patients that had a decrease in ICT and serum ferritin as compared to the 12 week prescreening timeframe [ Time Frame: Baseline to Week 36, Weeks 24 to 36 ]
    a. Proportion of patients that had a decrease in ICT and serum ferritin as compared to the 12 week prescreening timeframe

  5. NTDT Patients:Mean change in HbF [ Time Frame: Baseline to Week 24, Week 12 to 24, Week 24 to 36 ]
    a. Mean change in HbF

  6. NTDT Patients: Mean change in percent HbF [ Time Frame: Baseline to Week 24, Week 12 to 24, Week 24 to 36 ]
    a. Mean change in percent HbF

  7. NTDT Patients: Mean change in HbF over a continuous 12-week interval in the absence of a transfusion [ Time Frame: Baseline to Week 24, Week 12 to 24, Week 24 to 36 ]
    a. Mean change in HbF over a continuous 12-week interval in the absence of a transfusion

  8. NTDT Patients: Subject Response in HbF (increase of ≥3%) [ Time Frame: Baseline to Week 24, Week 12 to 24, Week 24 to 36 ]
    a. Subject Response in HbF (increase of ≥3%)

  9. NTDT Patients: Mean change in Hb [ Time Frame: Baseline to Week 12 to 24, Week 24 to 36 ]
    a. Mean change in Hb

  10. NTDT Patients: Mean change in Hb over a continuous 12-week interval in the absence of a transfusion [ Time Frame: Baseline to Week 12 to 24, Week 24 to 36 ]
    a. Mean change in Hb over a continuous 12-week interval in the absence of a transfusion

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

  12. TDT and NTDT Patients: PK Parameter Area Under the Plasma Concentration versus Time Curve (AUC) [ Time Frame: Baseline to Week 36 ]
    a. Area Under the Plasma Concentration versus Time Curve (AUC)

  13. TDT and NTDT Patients: PK Parameter Tmax [ Time Frame: Baseline to Week 36 ]
    a. Time to maximum concentration (tmax)

  14. TDT and NTDT Patients: PK Parameter t ½ [ Time Frame: Baseline to Week 36 ]
    a. Apparent terminal half-life t ½ (half-life)

  15. 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

  16. TDT and NTDT Patients: PK Parameter AUClast [ Time Frame: Baseline to Week 36 ]
    a. 0 to the last measurable timepoint (AUClast)

  17. TDT and NTDT Patients: PK Parameter AUC 0-infinity [ Time Frame: Baseline to Week 36 ]
    a. Extrapolated to infinity (AUC0-∞)


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. Concomitant single alpha gene deletion, duplication, or triplication is allowed.
  2. Documentation of dates of transfusions and the number of all RBC units within the 12 weeks prior to Screening.
  3. Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.
  4. ECOG performance score of 0-1
  5. Female subjects must not be pregnant, not be breast feeding, 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. Subjects on iron chelation therapy (ICT) at the time of ICF signing must have initiated the treatment with ICT at least 24 weeks before the predicted randomization date.
  7. Prior exposure to sotatercept, luspatercept, IMR-687, or gene therapy.
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


Contacts
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Contact: Caitlon Jacoby 617-206-2020 trials@imaratx.com
Contact: Joelle Lufkin 617-206-2020 trials@imaratx.com

Locations
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United States, California
The Oncology Institute Long Beach Recruiting
Long Beach, California, United States, 90805
Contact: Omkar Marathe, MD    562-232-0550      
France
Hôpital Necker-Enfants Malades Recruiting
Paris, France, 2401
Contact: Laure Joseph    +33 1 71 19 64 35      
Georgia
M. Zodelava Hematology Centre Recruiting
Tbilisi, Georgia, 0112
Contact: Mamia Zodelava, MD    +995599106010      
National Center of Surgery Recruiting
Tbilisi, Georgia, 0159
Contact: Levani Makhaldiani, MD    +995599773340      
Medinvest - Institute of Hematology and Transfusiology Recruiting
Tbilisi, Georgia, 0186
Contact: Genadi Iosava, MD    +995577411239      
Israel
Shaare Zedek Medical Center Recruiting
Jerusalem, Israel, 1205
Contact: Hagit Miskin    +972-2-5645681      
Hadassah University Hospital Ein Kerem Recruiting
Jerusalem, Israel, 9112001
Contact: Neta Goldschmidt, MD    +97226776744      
Galilee Medical Center Recruiting
Nahariya, Israel, 2210001
Contact: Amir Kuperman, MD    +972 507887457      
Sponsors and Collaborators
Imara, Inc.
Investigators
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Study Director: Eleanor Lisbon, MD, MPH 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: October 23, 2020
Last Verified: October 2020

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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