A Study of IMR-687 in Subjects With Beta Thalassemia

NCT ID: NCT04411082

Last Updated: 2025-05-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-16
• Study Completion Date: 2022-05-04

Brief Summary

A Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia

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).

Conditions

β Thalassemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lower Dose IMR-687

Oral administration of once daily IMR-687

Group Type: EXPERIMENTAL

IMR-687

Intervention Type: DRUG

Oral administration of once daily IMR-687

Higher dose IMR-687

Oral administration of once daily IMR-687

Group Type: EXPERIMENTAL

IMR-687

Intervention Type: DRUG

Oral administration of once daily IMR-687

Placebo

Oral administration of once daily placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral administration of once daily Placebo

Interventions

IMR-687

Oral administration of once daily IMR-687

Intervention Type: DRUG

Placebo

Oral administration of once daily Placebo

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imara, Inc.

INDUSTRY

Sponsor Role: collaborator

Cardurion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steve Luperchio

Role: STUDY_DIRECTOR

Cardurion Pharmaceuticals

Locations

Herlev Hospital

Herlev, Capital Region, Denmark

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, Haute-Garonn, France

Hôpital Edouard Herriot

Lyon, Rhone, France

Hôpital Necker-Enfants Malades

Paris, , France

M. Zodelava Hematology Centre

Tbilisi, Borjomi, Georgia

National Center of Surgery

Tbilisi, , Georgia

Medinvest - Institute of Hematology and Transfusiology

Tbilisi, , Georgia

Aghia Sofia General Children's Hospital

Athens, Attica, Greece

Laiko General Hospital of Athens

Athens, Attica, Greece

Ippokrateio General Hospital of Thessaloniki

Thessaloniki, Central Macedonia, Greece

University General Hospital of Patras

Patra, Peloponnese, Greece

Rambam Health Care Campus

Haifa, Haifa District, Israel

Hadassah University Hospital Ein Kerem

Jerusalem, Jerusalem, Israel

The Galilee Medical Center

Nahariya, Northern District, Israel

Emek Medical Center

Afula, , Israel

Azienda Ospedaliera Giuseppe Brotzu

Orbassano, Turin, Italy

Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli

Orbassano, Turin, Italy

Chronic Care Center

Hazmiyeh, , Lebanon

Hospital Sultanah Aminah Johor Bharu

Johor Bahru, Johor, Malaysia

Hospital Sultanah Bahiyah

Alor Star, Kedah, Malaysia

Hospital Raja Permaisuri Bainun

Ipoh, Perak, Malaysia

Hospital Pulau Pinang

George Town, Pulau Pinang, Malaysia

Hospital Queen Elizabeth - Kota Kinabalu

Kota Kinabalu, Sabah, Malaysia

Hospital Umum Sarawak

Kuching, Sarawak, Malaysia

Hôpital d'Enfants Rabat

Rabat, , Morocco

Amsterdam Universitair Medische Centra - Academisch Medisch Centrum

Amsterdam, North Holland, Netherlands

Centre Hôpital Universitaire Farhat Hached

Sousse, , Tunisia

Centre National de Greffe de la Moelle Osseuse

Tunis, , Tunisia

Hospital Aziza Othmana

Tunis, , Tunisia

Akdeniz Üniversitesi

Mersin, Mersin, Turkey (Türkiye)

Mersin Üniversitesi Tıp Fakültesi

Mersin, Mersin, Turkey (Türkiye)

Hacettepe Üniversitesi

Ankara, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi

Izmir, , Turkey (Türkiye)

Whittington Health NHS Trust

London, England, United Kingdom

University College London Hospitals NHS Foundation Trust

London, England, United Kingdom

Manchester University NHS Foundation Trust

Manchester, England, United Kingdom

Countries

Denmark; France; Georgia; Greece; Israel; Italy; Lebanon; Malaysia; Morocco; Netherlands; Tunisia; Turkey (Türkiye); United Kingdom

References

Foong WC, Loh CK, Ho JJ, Lau DS. Foetal haemoglobin inducers for reducing blood transfusion in non-transfusion-dependent beta-thalassaemias. Cochrane Database Syst Rev. 2023 Jan 13;1(1):CD013767. doi: 10.1002/14651858.CD013767.pub2.

Reference Type: DERIVED

PMID: 36637054 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002989-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IMR-BTL-201

Identifier Type: -

Identifier Source: org_study_id