A Study of IMR-687 in Subjects With Sickle Cell Disease
- Registration Number
- NCT04474314
- Lead Sponsor
- Cardurion Pharmaceuticals, Inc.
- Brief Summary
A Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects with Sickle Cell Disease
- Detailed Description
A phase 2b, randomized, double-blind, placebo-controlled, multicenter study of subjects with sickle cell disease (SCD; homozygous sickle hemoglobin \[HbSS\], sickle-β0 \[HbSβ0\] thalassemia, or sickle-β+ \[HbSβ+\] thalassemia) to evaluate the safety and efficacy of the phosphodiesterase type 9 (PDE9) inhibitor, IMR-687, administered once daily (qd) for 52 weeks.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 115
- Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia)
- Hemoglobin of >5.5 and <10.5 g/dL; Hb values within 21 days post-transfusion will be excluded.
- Subjects must have had at least 2 and no more than 12 documented episodes of VOCs in the past 12 months at the time of informed consent signing and at randomization (Day 1).
- Subjects receiving HU must have received it continuously for at least 6 months prior to signing informed consent, and must have been on a stable dose for at least 3 months prior to signing the informed consent, with no anticipated need for dose adjustments during the study including the screening period, in the opinion of the investigator.
- Female subjects must not be pregnant or breastfeeding and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner.
- Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.
- Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4 days prior to randomization (Day 1).
- Subjects participating in a chronic/prophylactic RBC transfusion program (i.e., regularly scheduled RBC transfusions); any transfusions within 21 days of screening or baseline Hb measurements
- Subjects with HbF >25% at screening.
- Significant kidney disease (eGFR <45mL/min) and liver dysfunction: alanine aminotransferase or aspartate aminotransferase >3x upper limit of normal.
- Body mass index (BMI) <17.0 kg/m2 and a total body weight <45 kg; or a 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 within 24 weeks prior to randomization (Day 1).
- Prior exposure to IMR-687.
- Subjects taking direct acting oral anti-coagulants (apixaban, dabigatran, rivaroxaban, edoxaban, or ticagrelor) or taking warfarin unless they stopped the treatment at least 28 days prior to randomization (Day 1).
- A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months prior to signing the informed consent.
- Receipt of erythropoietin, luspatercept (Reblozyl®)or other hematopoietic growth factor treatment within 3 months of signing the ICF or anticipated need for such agents during the study.
- Prior gene therapy.
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 Placebo Placebo Oral administration of once daily Placebo Higher dose IMR-687 IMR-687 Oral administration of once daily IMR-687
- Primary Outcome Measures
Name Time Method Effect on the Incidence of Vaso-occlusive Crises (VOCs) Baseline to Week 52 Annualized rate of VOCs. For each subject, the total number of VOCs on treatment were divided by the time on treatment divided by 52 weeks. The median was then summarized.
Proportion of Patients With Adverse Events and Serious Adverse Events Baseline to Week 56 Incidence of Adverse Events Incidence of Serious Adverse Events
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (49)
Guy's and Saint Thomas' NHS Foundation Trust
🇬🇧London, England, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧London, England, United Kingdom
Uganda Cancer Institute
🇺🇬Kampala, Uganda
Infectious Diseases Research Collaboration - Tororo
🇺🇬Tororo, Uganda
Jinja Regional Referral Hospital
🇺🇬Jinja, Uganda
Makerere University College of Health Sciences
🇺🇬Kampala, Uganda
The University of Illinois at Chicago College of Medicine
🇺🇸Chicago, Illinois, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Laiko General Hospital of Athens
🇬🇷Athens, Attica, Greece
University of Connecticut Health Main Building
🇺🇸Farmington, Connecticut, United States
University of Alabama at Birmingham School of Medicine - 1917 Clinic
🇺🇸Birmingham, Alabama, United States
University General Hospital of Patras
🇬🇷Patra, Greece
Arkansas Primary Care Clinic
🇺🇸Little Rock, Arkansas, United States
Center For Inherited Blood Disorders
🇺🇸Santa Ana, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
University of California San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Korle Bu Teaching Hospital
🇬🇭Accra, Ghana
Kintampo Health Research Centre
🇬🇭Kintampo, Ghana
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
🇮🇹Turin, Orbassano, Italy
Kenya Medical Research Institute - Kisumu
🇰🇪Kisumu, Nyanza, Kenya
Hopital Nini
🇱🇧Tripoli, North Governorate, Lebanon
Joint Clinical Research Center - Lubowa
🇺🇬Kampala, Uganda
Chronic Care Center
🇱🇧Hazmiyeh, Lebanon
Hôpital d'Enfants Rabat
🇲🇦Rabat, Morocco
Centre Hôpital Universitaire Farhat Hached
🇹🇳Sousse, Tunisia
Hospital Aziza Othmana
🇹🇳Tunis, Tunisia
Manchester University NHS Foundation Trust
🇬🇧Manchester, England, United Kingdom
The Oncology Institute Long Beach
🇺🇸Whittier, California, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Baylor Scott & White Medical Center-Temple
🇺🇸Temple, Texas, United States
Weill Cornell Medicine - Center for Blood Disorders
🇺🇸New York, New York, United States
Ippokrateio General Hospital of Thessaloniki
🇬🇷Thessaloníki, Greece
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Rome, Italy
Ente Ospedaliero Ospedali Galliera
🇮🇹Genoa, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
🇮🇹Palermo, Italy
Hagaziekenhuis Van Den Haag - Leyweg
🇳🇱Den Haag, South Holland, Netherlands
The Centre for Respiratory Diseases Research - Kenya Medical Research Institute
🇰🇪Nairobi, Kenya
Centre National De Transfusion Sanguine - Du Senegal
🇸🇳Dakar, Senegal
Hedi Chaker Hospital
🇹🇳Sfax, Tunisia
Sultan Qaboos University Hospital
🇴🇲Muscat, Oman
Centre National de Greffe de la Moelle Osseuse
🇹🇳Tunis, Tunisia
University Hospitals Bristol NHS Foundation Trust
🇬🇧Bristol, England, United Kingdom
University College London Hospitals NHS
🇬🇧London, England, United Kingdom
American University of Beirut Medical Center
🇱🇧Beirut, Lebanon
Virginia Commonwealth University Health - Ambulatory Care Center
🇺🇸Richmond, Virginia, United States
Gertrude's Children's Hospital
🇰🇪Nairobi, Kenya
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, England, United Kingdom