A Study of IMR-687 in Subjects With Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04474314
• Other study ID #: IMR-SCD-301
• Secondary ID: 2019-004471-39
• Status: Terminated
• Phase: Phase 2
• Start date: August 13, 2020
• Est. completion date: May 4, 2022

Study information

• Verified date: July 2022
• Source: Imara, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects with Sickle Cell Disease

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 information / eligibility

• Status: Terminated
• Enrollment: 115
• Est. completion date: May 4, 2022
• Est. primary completion date: March 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• IMR-687
Oral administration of once daily IMR-687
• Placebo
Oral administration of once daily Placebo

Locations

Country	Name	City	State
Ghana	Korle Bu Teaching Hospital	Accra
Ghana	Kintampo Health Research Centre	Kintampo
Greece	Laiko General Hospital of Athens	Athens	Attica
Greece	University General Hospital of Patras	Patra
Greece	Ippokrateio General Hospital of Thessaloniki	Thessaloníki
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	Fondazione Policlinico Universitario Agostino Gemelli	Roma	Rome
Italy	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Turin	Orbassano
Kenya	Kenya Medical Research Institute - Kisumu	Kisumu	Nyanza
Kenya	Gertrude's Children's Hospital	Nairobi
Kenya	The Centre for Respiratory Diseases Research - Kenya Medical Research Institute	Nairobi
Lebanon	American University of Beirut Medical Center	Beirut
Lebanon	Chronic Care Center	Hazmiyeh
Lebanon	Hopital Nini	Tripoli	North Governorate
Morocco	Hôpital d'Enfants Rabat	Rabat
Netherlands	Hagaziekenhuis Van Den Haag - Leyweg	Den Haag	South Holland
Oman	Sultan Qaboos University Hospital	Muscat
Senegal	Centre National De Transfusion Sanguine - Du Senegal	Dakar
Tunisia	Hedi Chaker Hospital	Sfax
Tunisia	Centre Hôpital Universitaire Farhat Hached	Sousse
Tunisia	Centre National de Greffe de la Moelle Osseuse	Tunis
Tunisia	Hospital Aziza Othmana	Tunis
Uganda	Jinja Regional Referral Hospital	Jinja
Uganda	Joint Clinical Research Center - Lubowa	Kampala
Uganda	Makerere University College of Health Sciences	Kampala
Uganda	Uganda Cancer Institute	Kampala
Uganda	Infectious Diseases Research Collaboration - Tororo	Tororo
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol	England
United Kingdom	Guy's and Saint Thomas' NHS Foundation Trust	London	England
United Kingdom	King's College Hospital NHS Foundation Trust	London	England
United Kingdom	University College London Hospitals NHS	London	England
United Kingdom	Manchester University NHS Foundation Trust	Manchester	England
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford	England
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham School of Medicine - 1917 Clinic	Birmingham	Alabama
United States	The University of Illinois at Chicago College of Medicine	Chicago	Illinois
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	University of Connecticut Health Main Building	Farmington	Connecticut
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Arkansas Primary Care Clinic	Little Rock	Arkansas
United States	Weill Cornell Medicine - Center for Blood Disorders	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Virginia Commonwealth University Health - Ambulatory Care Center	Richmond	Virginia
United States	Center For Inherited Blood Disorders	Santa Ana	California
United States	Baylor Scott & White Medical Center-Temple	Temple	Texas
United States	The Oncology Institute Long Beach	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Imara, Inc.

Countries where clinical trial is conducted

United States,  Ghana,  Greece,  Italy,  Kenya,  Lebanon,  Morocco,  Netherlands,  Oman,  Senegal,  Tunisia,  Uganda,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect on the Incidence of Vaso-occlusive Crises (VOCs)	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.	Baseline to Week 52
Primary	Proportion of Patients With Adverse Events and Serious Adverse Events	Incidence of Adverse Events Incidence of Serious Adverse Events	Baseline to Week 56