A Study of IMR-687 in Subjects With Beta Thalassemia
- Registration Number
- NCT04411082
- Lead Sponsor
- Cardurion Pharmaceuticals, Inc.
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 122
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lower Dose IMR-687 IMR-687 Oral administration of once daily IMR-687 Higher dose IMR-687 IMR-687 Oral administration of once daily IMR-687 Placebo Placebo Oral administration of once daily placebo
- Primary Outcome Measures
Name Time Method IMR-687 Safety and Tolerability Baseline to Week 40 Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events
- Secondary Outcome Measures
Name Time Method TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24 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. 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 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 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 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 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 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 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
Trial Locations
- Locations (36)
Hospital Sultanah Aminah Johor Bharu
🇲🇾Johor Bahru, Johor, Malaysia
Herlev Hospital
🇩🇰Herlev, Hovedstaden, Denmark
Hôpital Edouard Herriot
🇫🇷Lyon Cedex 03, Rhone, France
Hôpital Necker-Enfants Malades
🇫🇷Paris, France
Hadassah University Hospital Ein Kerem
🇮🇱Jerusalem, Jerusalem District, Israel
The Galilee Medical Center
🇮🇱Nahariya, Northern District, Israel
Hospital Umum Sarawak
🇲🇾Kuching, Sarawak, Malaysia
Hospital Queen Elizabeth - Kota Kinabalu
🇲🇾Kota Kinabalu, Sabah, Malaysia
Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
🇮🇹Orbassano, Turin, Italy
Chronic Care Center
🇱🇧Hazmiyeh, Lebanon
Hospital Pulau Pinang
🇲🇾George Town, Penang, Malaysia
Hôpital d'Enfants Rabat
🇲🇦Rabat, Morocco
Akdeniz Üniversitesi
🇹🇷Mersin, Icel, Turkey
Hacettepe Üniversitesi
🇹🇷Ankara, Turkey
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
Mersin Üniversitesi Tıp Fakültesi
🇹🇷Mersin, Icel, Turkey
Whittington Health NHS Trust
🇬🇧London, England, United Kingdom
Manchester University NHS Foundation Trust
🇬🇧Manchester, England, United Kingdom
Institut Universitaire du Cancer de Toulouse Oncopole
🇫🇷Toulouse cedex 9, Haute-Garonn, France
National Center of Surgery
🇬🇪Tbilisi, Georgia
Medinvest - Institute of Hematology and Transfusiology
🇬🇪Tbilisi, Georgia
University General Hospital of Patras
🇬🇷Patra, Peloponnese, Greece
Ege Universitesi Tip Fakultesi
🇹🇷Izmir, Turkey
M. Zodelava Hematology Centre
🇬🇪Tbilisi, Borjomi, Georgia
Aghia Sofia General Children's Hospital
🇬🇷Athens, Attica, Greece
Emek Medical Center
🇮🇱Afula, Israel
Azienda Ospedaliera Giuseppe Brotzu
🇮🇹Orbassano, Turin, Italy
Laiko General Hospital of Athens
🇬🇷Athens, Attica, Greece
Ippokrateio General Hospital of Thessaloniki
🇬🇷Thessaloníki, Central Macedonia, Greece
Rambam Health Care Campus
🇮🇱Haifa, Haifa District, Israel
Hospital Raja Permaisuri Bainun
🇲🇾Ipoh, Perak, Malaysia
University College London Hospitals NHS Foundation Trust
🇬🇧London, England, United Kingdom
Hospital Sultanah Bahiyah
🇲🇾Alor Setar, Kedah, Malaysia