Clinical trial NCT04411082: A Study of IMR-687 in Subjects With Beta Thalassemia
Official title: A Phase 2 Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects With Beta Thalassemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: β Thalassemia
Keywords: Transfusion
TDT
NTDT
Lead sponsor: Cardurion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Imara, Inc.
First posted: 2020-06-02
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: IMR-687 Safety and Tolerability
timeFrame: Baseline to Week 40
Secondary outcomes:
measure: TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24
timeFrame: Baseline to Week 24
measure: NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.
timeFrame: Baseline to Week 24
measure: 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
timeFrame: Baseline to Week 24
measure: TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36
timeFrame: Baseline to Week 36
measure: TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24
timeFrame: Baseline to Week 24
measure: TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36
timeFrame: Baseline to Week 36
measure: NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions
timeFrame: Baseline to Week 36
measure: 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
timeFrame: Baseline to Week 36
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Herlev Hospital
state: Hovedstaden
city: Toulouse cedex 9
country: France
facility: Institut Universitaire du Cancer de Toulouse Oncopole
state: Haute-Garonn
city: Lyon Cedex 03
country: France
facility: Hôpital Edouard Herriot
state: Rhone
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Tbilisi
country: Georgia
facility: M. Zodelava Hematology Centre
state: Borjomi
city: Tbilisi
country: Georgia
facility: National Center of Surgery
city: Tbilisi
country: Georgia
facility: Medinvest - Institute of Hematology and Transfusiology
city: Athens
country: Greece
facility: Aghia Sofia General Children's Hospital
state: Attica
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
state: Attica
city: Thessaloníki
country: Greece
facility: Ippokrateio General Hospital of Thessaloniki
state: Central Macedonia
city: Patra
country: Greece
facility: University General Hospital of Patras
state: Peloponnese
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: Haifa District
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
state: Jerusalem District
city: Nahariya
country: Israel
facility: The Galilee Medical Center
state: Northern District
city: Afula
country: Israel
facility: Emek Medical Center
city: Orbassano
country: Italy
facility: Azienda Ospedaliera Giuseppe Brotzu
state: Turin
city: Orbassano
country: Italy
facility: Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
state: Turin
city: Hazmiyeh
country: Lebanon
facility: Chronic Care Center
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah Johor Bharu
state: Johor
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah
state: Kedah
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
state: Penang
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
state: Perak
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth - Kota Kinabalu
state: Sabah
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
state: Sarawak
city: Rabat
country: Morocco
facility: Hôpital d'Enfants Rabat
city: Amsterdam
country: Netherlands
facility: Amsterdam Universitair Medische Centra - Academisch Medisch Centrum
state: North Holland
city: Sousse
country: Tunisia
facility: Centre Hôpital Universitaire Farhat Hached
city: Tunis
country: Tunisia
facility: Centre National de Greffe de la Moelle Osseuse
city: Tunis
country: Tunisia
facility: Hospital Aziza Othmana
city: Mersin
country: Turkey
facility: Akdeniz Üniversitesi
state: Icel
city: Mersin
country: Turkey
facility: Mersin Üniversitesi Tıp Fakültesi
state: Icel
city: Ankara
country: Turkey
facility: Hacettepe Üniversitesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: London
country: United Kingdom
facility: Whittington Health NHS Trust
state: England
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
state: England
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
state: England
Study officials:
affiliation: Cardurion Pharmaceuticals
name: Steve Luperchio
role: STUDY_DIRECTOR
References: