A Study of IMR-687 in Subjects With Beta Thalassemia

A Phase 2 Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects With Beta Thalassemia

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

Study Overview

• Status: Terminated
• Conditions: β Thalassemia
• Intervention / Treatment: Drug: IMR-687; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Hovedstaden
    • Herlev, Hovedstaden, Denmark, 2730
      • Herlev Hospital
• France
  • Paris, France, 75015
    • Hôpital Necker-Enfants Malades
  • Haute-Garonn
    • Toulouse cedex 9, Haute-Garonn, France, 31059
      • Institut Universitaire du Cancer de Toulouse Oncopole
  • Rhone
    • Lyon Cedex 03, Rhone, France, 69437
      • Hôpital Edouard Herriot
• Georgia
  • Tbilisi, Georgia, 0159
    • National Center of Surgery
  • Tbilisi, Georgia, 0186
    • Medinvest - Institute of Hematology and Transfusiology
  • Borjomi
    • Tbilisi, Borjomi, Georgia, 0112
      • M. Zodelava Hematology Centre
• Greece
  • Attica
    • Athens, Attica, Greece, 11527
      • Aghia Sofia General Children's Hospital
    • Athens, Attica, Greece, 11527
      • Laiko General Hospital of Athens
  • Central Macedonia
    • Thessaloníki, Central Macedonia, Greece, 54642
      • Ippokrateio General Hospital of Thessaloniki
  • Peloponnese
    • Patra, Peloponnese, Greece, 26504
      • University General Hospital of Patras
• Israel
  • Afula, Israel, 18101
    • Emek Medical Center
  • Haifa District
    • Haifa, Haifa District, Israel, 3109601
      • Rambam Health Care Campus
  • Jerusalem District
    • Jerusalem, Jerusalem District, Israel, 9112001
      • Hadassah University Hospital Ein Kerem
  • Northern District
    • Nahariya, Northern District, Israel, 2210001
      • The Galilee Medical Center
• Italy
  • Turin
    • Orbassano, Turin, Italy, 10043
      • Azienda Ospedaliera Giuseppe Brotzu
    • Orbassano, Turin, Italy, 10043
      • Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
• Lebanon
  • Hazmiyeh, Lebanon, 213
    • Chronic Care Center
• Malaysia
  • Johor
    • Johor Bahru, Johor, Malaysia, 80100
      • Hospital Sultanah Aminah Johor Bharu
  • Kedah
    • Alor Setar, Kedah, Malaysia, 05460
      • Hospital Sultanah Bahiyah
  • Penang
    • George Town, Penang, Malaysia, 10450
      • Hospital Pulau Pinang
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Hospital Raja Permaisuri Bainun
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Hospital Queen Elizabeth - Kota Kinabalu
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Hospital Umum Sarawak
• Morocco
  • Rabat, Morocco, 10100
    • Hôpital d'Enfants Rabat
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Amsterdam Universitair Medische Centra - Academisch Medisch Centrum
• Tunisia
  • Sousse, Tunisia, 4000
    • Centre Hôpital Universitaire Farhat Hached
  • Tunis, Tunisia, 1006
    • Centre National de Greffe de la Moelle Osseuse
  • Tunis, Tunisia, 1008
    • Hospital Aziza Othmana
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi
  • Izmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi
  • Icel
    • Mersin, Icel, Turkey, 33110
      • Akdeniz Universitesi
    • Mersin, Icel, Turkey, 33110
      • Mersin Üniversitesi Tıp Fakültesi
• United Kingdom
  • England
    • London, England, United Kingdom, N19 5NF
      • Whittington Health NHS Trust
    • London, England, United Kingdom, NW1 2PG
      • University College London Hospitals Nhs Foundation Trust
    • Manchester, England, United Kingdom, M13 9WL
      • Manchester University NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IMR-687 Safety and Tolerability	Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events	Baseline to Week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 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)	Baseline to Week 24
NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.	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.	Baseline to Week 24
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	Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions	Baseline to Week 24
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 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)	Baseline to Week 36
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 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)	Baseline to Week 24
TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 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)	Baseline to Week 36
NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions	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.	Baseline to Week 36
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	Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions	Baseline to Week 36

Collaborators and Investigators

• Sponsor: Imara, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2020
• Primary Completion (Actual): March 11, 2022
• Study Completion (Actual): May 4, 2022

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Transfusion; NTDT; TDT
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: IMR-BTL-201; 2019-002989-12 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No