Sickle Cell Disease MedDRA version: 21.0 Level: PT Classification code 10040644 Term: Sickle cell disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
IMARA, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female aged =18 to =65 years at the time of informed consent form (ICF) signing. 2.Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia) in the medical record; if not available, the diagnosis must be confirmed at the site’s local laboratory instead. 3.Subjects must have had at least 1 and no more than 12 documented episodes of VOC in the past 12 months at the time of ICF signing and at randomization (Day 1). For study eligibility, VOC is defined as a documented episode of an acute painful crisis (for which there was not an explanation other than VOC) that involved moderate to severe pain lasting for at least 2 hours and at least one of the following: •Use of escalated analgesia (including healthcare professional-instructed use of an analgesic prescription) •A hospital, emergency department, or clinic visit and/or healthcare telephone consultation at the time of occurrence •Diagnosis of acute chest syndrome (ACS) (defined as an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X ray), hepatic sequestration, or splenic sequestration 4.Hemoglobin (Hb) of >5.5 and =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1.Hospital discharge for sickle cell crisis or other vaso occlusive event within the 4 days prior to randomization (Day 1). 2.Red blood cell transfusion within 60 days of signing the ICF or on chronic transfusion therapy regimen. Transfusion status must be reassessed at randomization (Day 1). Note: If a subject requires a transfusion during the screening period, they may be rescreened up to one time. 3.Subjects with hereditary persistence of HbF (i.e., HbF >25% at screening). 4.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). 5.For female subjects of childbearing potential, a positive serum human chorionic gonadotropin (hCG) test (screening) or a positive urine hCG test at randomization (Day 1). 6.Estimated glomerular filtration rate (eGFR) 3 × the upper limit of normal. 8.Body mass index (BMI) 35 kg/m2. 9.Current or history of malignancies (solid tumors and hematological malignancies), unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for =5 years. However, subjects with the following history/concurrent conditions are allowed if, in the opinion of the investigator, the condition has been adequately diagnosed and is determined to be clinically in remission, and the subject’s participation in the study would not represent a safety concern: a.Basal or squamous cell carcinoma of the skin b.Carcinoma in situ of the cervix c.Carcinoma in situ of the breast d.Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis clinical staging system) 10.A history of a clinically significant allergic reaction or hypersensitivity, as judged by the investigator, to any drug or any component of the study drug formulations used in the study (see Investigator’s Brochure). 11.History of unstable or deteriorating cardiac or pulmonary disease within 6 months before signing the ICF, including but not limited to the following: a.Unstable angina pectoris or myocardial infarction or elective coronary intervention b.Congestive heart failure requiring hospitalization c.Uncontrolled clinically significant arrhythmias 12.Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable). 13.On ECG testing at ICF signing and/or randomization (Day 1), a corrected QT interval, Fridericia’s formula (QTcF) >450 ms in men and >470 ms in women or the presence of clinically significant ECG abnormalities as determined by the investigator. 14.A history of major surgery within 4 weeks or minor surgery within 2 weeks of randomization (Day 1). 15.Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1). 16.Subjects taking direct acting oral anti-coagulants (DOACs) apixaban, dabigatran, rivaroxaban, edoxaban, or ticagrelor, or taking warfarin, are excluded due to the possibility of a cytochrome P450 (CYP)3A-mediated drug interaction, unless they stopped the treatment at least 28 days prior to randomization (Day 1); other oral anti coagulants and anti-platelet drugs ar
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the fetal hemoglobin (HbF) response to IMR-687 versus placebo •To evaluate the safety of IMR-687 versus placebo ;Secondary Objective: Secondary Efficacy Objectives •To evaluate the effect of IMR-687 versus placebo on HbF associated biomarkers •To evaluate the effect of IMR-687 versus placebo on indices of red cell hemolysis •To evaluate the effect of IMR-687 versus placebo on indices of white blood cell (WBC) adhesion •To evaluate the effect of IMR-687 versus placebo on the incidence of vaso-occlusive crises (VOCs) •To evaluate the effect of IMR-687 versus placebo on quality of life measures Pharmacokinetic Objectives •To evaluate the PK of IMR-687 and any major circulating metabolites Exploratory Efficacy Objectives •To evaluate the effect of IMR-687 versus placebo on changes in red blood cell (RBC) characteristics and total Hb •To evaluate the effect of IMR-687 versus placebo on renal function •To evaluate the effect of IMR-687 versus placebo on indices associated with cardiovascular pathophysiology and ischemic stroke risk ;Primary end point(s): Primary Efficacy Endpoint: Subject response as defined by an increase of =3% in HbF from baseline to Week 24 Primary Safety Endpoints: AEs, SAEs, clinically significant changes in laboratory tests, clinically significant changes in vital signs, and clinically significant changes in ECGs;Timepoint(s) of evaluation of this end point: Primary Efficacy: An interim analysis (IA) will be performed after 33 subjects have reached Week 24, and a primary analysis will be performed after all subjects have reached Week 24 or terminated early. A final analysis will be conducted at study completion (i.e., when all subjects have reached Week 56 or terminated early). Primary Safety Endpoints: throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: •Change in HbF from baseline to Week 24, Week 36, and Week 52 •Subject response as defined by an increase of =3% in HbF from baseline to Week 36 and Week 52 •Change in % F cells from baseline to Week 24, Week 36, and Week 52 •Change in hemolysis markers (% and absolute reticulocytes) and related measures (unconjugated bilirubin and lactate dehydrogenase [LDH]) from baseline to Week 24, Week 36, and Week 52 •Change in soluble E-selectin (E-sel), P-selectin (P-sel), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and myeloperoxidase (MPO) from baseline to Weeks 24, 36, and 52 •Change in the number of VOCs from baseline to Week 24, Week 36, and Week 52 VOC is defined as a documented episode of an acute painful crisis (for which there was not an explanation other than VOC) that involves moderate to severe pain lasting for at least 2 hours and at least one of the following: - Use of escalated analgesia (including healthcare professional-instructed use of an analgesic prescription). - A hospital, emergency department, or clinic visit and/or healthcare telephone consultation at the time of occurrence - Diagnosis of ACS (defined as an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray), hepatic sequestration, or splenic sequestration •Change in each measured subdomain of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®) questionnaire from baseline to Week 24, Week 36, and Week 52 •Change in total preference score and individual domain scores of the Patient-Reported Outcomes Measurements Information System – Preference (PROMIS® 29 + 2 Profile v2.1 [PROPr]) questionnaire from baseline to Week 24, Week 36, and Week 52 •Change in overall score of the Sickle Cell Self-Efficacy Scale (SCSES) from baseline to Week 24, Week 36, and Week 52 Pharmacokinetic endpoints: •PK | — |
Countries
Egypt, France, Ghana, Greece, Israel, Kenya, Lebanon, Morocco, Netherlands, Oman, Senegal, Tunisia, Uganda, United Kingdom, United States
Contacts
Public ContactKevin B. Johnson
IMARA, Inc.
Outcome results
None listed