A phase 2a Study in Adult Volunteers with Sickle Cell Anaemia - 001
Research type
Research Study
Full title
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study of IMR-687 in Adult Patients with Sickle Cell Anaemia (Homozygous HbSS or Sickle-β0 Thalassemia)
IRAS ID
224732
Contact name
Craig McCarthy
Contact email
Sponsor organisation
Imara, Inc
Eudract number
2017-000653-39
Duration of Study in the UK
1 years, 5 months, 25 days
Research summary
Summary of Research
Patients with sickle cell anaemia (SCA) make an abnormal protein called hemoglobin S, which causes their red blood cells to change shape (i.e.,‘sickling’) and get stuck in small blood vessels and cause serious clogs in these vessels. The overall result of these blockages in the blood vessels is to cause pain, as well as strokes, extreme difficulty with chest pain and breathing and other organ damage. Hydroxyurea (HU) is an available, but difficult to use drug that can increase the patient’s level of an alternative hemoglobin protein, called hemoglobin F (HbF). HbF can work more like normal hemoglobin, so that patients can have more normal red blood cells, and therefore reduce pain.
Imara developed IMR-687 as a chemical that can increase HbF in animals, as well as reduce the formation of red blood cell sickling and therefore blood vessel blockages. IMR-687 has been given to 50 healthy volunteers previously and appears safe and well-tolerated.
This study aims to test the safety of IMR-687 in sickle cell patients, and to explore if it may increase HbF. The study will also measure the way the drug is handled by the body (i.e., pharmacokinetics). Patients with SCA, between the ages of 18 and 50 years old, will take IMR-687 once daily for 16-24 weeks. Blood samples will be taken at set timepoints and patients will be asked about any side effects, and any changes in the pain caused by their disease.
Summary of Results
Study IMR-SCD-102 evaluated the safety, tolerability, and clinical outcomes of an investigational drug called IMR-687 administered once daily for 16 to 24 weeks in patients with sickle cell disease. Some patients received the active drug and some received placebo (inactive drug), which was not known until the end of the study. Of the 93 patients treated in the study, 35 were also receiving treatment with hydroxyurea. IMR-687 was generally well-tolerated, with or without hydroxyurea background therapy, at IMR-687 doses up to 200 mg daily. IMR-687 did not appear to interfere with hydroxyurea treatment. Exploratory analysis of the study demonstrated an increase in the number of red blood cells containing fetal hemoglobin with IMR-687 as compared to placebo, which can impact the red blood cell abnormalities that are characteristic of the disease. A decreased rate of vaso-occlusive (painful) crises (VOCs) was also observed, as well as a delay in the time to first VOC on study and a reduction in VOC-related hospitalizations. In a patient-reported questionnaire, the Adult Sickle Cell Quality of Life Measurement (ASCQ-Me), a reduction in pain episode severity was observed in the higher dose group as compared to placebo.
REC name
London - London Bridge Research Ethics Committee
REC reference
17/LO/1476
Date of REC Opinion
19 Oct 2017
REC opinion
Further Information Favourable Opinion