Clinical trial NCT04474314: A Study of IMR-687 in Subjects With Sickle Cell Disease
Official title: A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease
Lead sponsor: Cardurion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Imara, Inc.
First posted: 2020-07-16
Enrollment: 115
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 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.

Eligibility criteria: Inclusion Criteria:

1. Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia)
2. Hemoglobin of \>5.5 and \<10.5 g/dL; Hb values within 21 days post-transfusion will be excluded.
3. 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).
4. 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.
5. Female subjects must not be pregnant or breastfeeding and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner.
6. Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.

Exclusion Criteria:

1. Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4 days prior to randomization (Day 1).
2. 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
3. Subjects with HbF \>25% at screening.
4. Significant kidney disease (eGFR \<45mL/min) and liver dysfunction: alanine aminotransferase or aspartate aminotransferase \>3x upper limit of normal.
5. Body mass index (BMI) \<17.0 kg/m2 and a total body weight \<45 kg; or a BMI \>35 kg/m2.
6. 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).
7. Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1).
8. Prior exposure to IMR-687.
9. 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).
10. A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months prior to signing the informed consent.
11. 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.
12. Prior gene therapy.

Primary outcomes:
measure: Effect on the Incidence of Vaso-occlusive Crises (VOCs)
timeFrame: Baseline to Week 52
measure: Proportion of Patients With Adverse Events and Serious Adverse Events
timeFrame: Baseline to Week 56
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine - 1917 Clinic
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Santa Ana
country: United States
facility: Center For Inherited Blood Disorders
state: California
city: Whittier
country: United States
facility: The Oncology Institute Long Beach
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Main Building
state: Connecticut
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: The University of Illinois at Chicago College of Medicine
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine - Center for Blood Disorders
state: New York
city: Temple
country: United States
facility: Baylor Scott & White Medical Center-Temple
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Health - Ambulatory Care Center
state: Virginia
city: Accra
country: Ghana
facility: Korle Bu Teaching Hospital
city: Kintampo
country: Ghana
facility: Kintampo Health Research Centre
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
state: Attica
city: Patra
country: Greece
facility: University General Hospital of Patras
city: Thessaloníki
country: Greece
facility: Ippokrateio General Hospital of Thessaloniki
city: Turin
country: Italy
facility: Azienda Ospedaliero - Universitaria San Luigi Gonzaga
state: Orbassano
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
state: Rome
city: Genoa
country: Italy
facility: Ente Ospedaliero Ospedali Galliera
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
city: Kisumu
country: Kenya
facility: Kenya Medical Research Institute - Kisumu
state: Nyanza
city: Nairobi
country: Kenya
facility: Gertrude's Children's Hospital
city: Nairobi
country: Kenya
facility: The Centre for Respiratory Diseases Research - Kenya Medical Research Institute
city: Tripoli
country: Lebanon
facility: Hopital Nini
state: North Governorate
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Hazmiyeh
country: Lebanon
facility: Chronic Care Center
city: Rabat
country: Morocco
facility: Hôpital d'Enfants Rabat
city: Den Haag
country: Netherlands
facility: Hagaziekenhuis Van Den Haag - Leyweg
state: South Holland
city: Muscat
country: Oman
facility: Sultan Qaboos University Hospital
city: Dakar
country: Senegal
facility: Centre National De Transfusion Sanguine - Du Senegal
city: Sfax
country: Tunisia
facility: Hedi Chaker Hospital
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: Jinja
country: Uganda
facility: Jinja Regional Referral Hospital
city: Kampala
country: Uganda
facility: Uganda Cancer Institute
city: Kampala
country: Uganda
facility: Makerere University College of Health Sciences
city: Kampala
country: Uganda
facility: Joint Clinical Research Center - Lubowa
city: Tororo
country: Uganda
facility: Infectious Diseases Research Collaboration - Tororo
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: University College London Hospitals NHS
state: England
city: London
country: United Kingdom
facility: Guy's and Saint Thomas' NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
state: England
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
state: England
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: England
Study officials:
affiliation: Imara, Inc.
name: Kenneth Attie, MD
role: STUDY_DIRECTOR
References: