A Phase 2a Study of IMR-687 in Adult volunteers with Sickle Cell Anaemia.
- Conditions
- Sickle cell disease (SCD) is a rare inherited red blood cell (RBC) disorder characterized by chronic hemolysis, debilitating pain, progressive multiorgan damage, and premature death. SCD is caused by a specific point mutation in the gene encoding hemoglobin subunit beta that results in the substitution of a hydrophobic valine residue for glutamic acid in the 6th position from the N-terminus of the beta-chain leading to the production of HbS.MedDRA version: 21.0Level: PTClassification code 10040644Term: Sickle cell diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-000653-39-GB
- Lead Sponsor
- Imara, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 54
Each patient must meet all of the following criteria to be enrolled in the study:
1. Male or female =18 or =50 years of age.
2. Confirmed diagnosis of SCA (HbSS or sickle-B0 thalassemia). Note, if not already documented in the patient’s record, the diagnosis of SCA must be confirmed via electrophoresis, HPLC, and/or genotyping.
3. Use of HU:
• For patients in the Population A: Have not received HU within 90 days prior to Screening and are not planning to take HU within the next 6 months
• For patients in Population B: Have received HU for at least 6 months, have been on a stable dose for at least 60 days prior to Screening, and are not planning to change the dose level, dose regimen, or discontinue HU within the next 6 months.
4. Female patients must not be pregnant and be highly unlikely to become pregnant. Male patients must be unlikely to impregnate a partner. Male or female patients must meet at least one of the following criteria:
• A female patient who is not of reproductive potential is eligible without requiring the use of contraception. A female patient who is not of reproductive potential is defined as one who: (1) has reached natural menopause (defined as 12 months of spontaneous amenorrhea without an alternative medical cause, and can be confirmed with serum follicle-stimulating hormone levels in the postmenopausal range as determined by the local laboratory; (2) is 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or (3) has undergone bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (i.e., anorexia nervosa).
• A male patient who is not of reproductive potential is eligible without requiring the use of contraception. A male patient who is not of reproductive potential is defined as one who has undergone a successful vasectomy. A successful vasectomy is defined as (1) microscopic documentation of azoospermia, or (2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post vasectomy.
• A male or female patient who is of reproductive potential agrees to remain truly abstinent or use (or have their partner use) acceptable methods of highly effective contraception starting from the time of consent through 3 months after the completion of study therapy. True abstinence is defined as abstinence that is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of the trial and withdrawal are not acceptable methods of contraception. Acceptable methods of highly effective birth control are combined or progestogen-only hormonal contraception that is associated with inhibition of ovulation, intrauterine device, and intrauterine hormone-releasing system.
5. Be capable of giving informed consent and reading and signing the informed consent form after the nature of the study has been fully explained by the investigator or investigator designee.
6. Be willing and able to complete all study assessments and procedures and to communicate effectively with the investigator and site staff.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Total Hb at Screening >12.5 g/dL or < 6 g/dL.
2.Reticulocyte count <100 x 109/L for Population A; reticulocyte count <80 x 109/L for Population
B.
3. >7 hospitalizations (for at least 24 hours) for vaso-occlusive crises (VOC), including acute chest syndrome (ACS) and priapism, within the prior year.
4. Blood transfusion or donation of blood or any blood product within 60 days of Day 1 or on chronic transfusion therapy regimen.
5. Positive for human immunodeficiency virus (HIV), hepatitis C (HCV) antibodies (unless the patient has successfully completed drug therapy that results in cure/clearance of HCV), and hepatitis B surface antigen.
6. For female patients of childbearing potential, a positive serum human chorionic gonadotropin (hCG) test (Screening) or a positive urine hCG test on Day 1.
7. Estimated glomerular filtration rate (eGFR) <50 mL/min as calculated by the equation from the Modification of Diet in Renal Disease (MDRD) Study using creatinine, age, sex, and ethnicity.
8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x the upper limit of normal (ULN)
9. Body Mass Index (BMI) < 17.5 or > 35 kg/m2; a total body weight < 50 kg
10. Use of PDE type 5 inhibitors (including but not limited to sildenafil, tadalafil, vardenafil) within 7 days prior to the first dose of study drug, or planning to use any time during study
11. A history of drug or alcohol abuse as judged by the investigator within the past 1year, or a positive alcohol (breathalyser) test (Screening or Day -1).
12. A cancer that has not been in complete remission for at least 5 years. Patients with squamous cell or basal cell carcinoma of the skin, localised cervical cancer, or localised prostate cancer are eligible if, in the opinion of the investigator, the condition has been adequately diagnosed, and is determined to be clinically in remission, and the patient’s participation in the study would not represent a safety concern.
13. 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.
14. On ECG, a corrected QT interval, Fridericia’s formula (QTcF) >450 ms in men and >470 ms in women or the presence of clinically significant abnormalities as determined by the investigator.
15. A history of major surgery within 4 weeks or minor surgery within 2 weeks of Day 1.
16. Any flu-like syndrome or other respiratory infection within 2 weeks of Day 1 or vaccination with attenuated live virus within 4 weeks of Day 1.
17. Participation in an investigational drug or device study within 30 days prior to Day 1.
18. Use within 30 days prior to Day 1, or planning to use during the study, of any drugs or substances that are known to strongly inhibit or induce cytochrome P450 (CYP) enzymes, including but not limited to cimetidine, cyclosporine, erythromycin, omeprazole, rifampin, ritonavir, and St. John’s wort. If there is any question as to whether a substance is permitted, please review the product labelling (if applicable) and consult the Sponsor.
19. Consumption of grapefruit, grapefruit juice, or grapefruit products within 24 hours prior to Day 1 or planning to consume grapefruit products during the study.
20. Use within 30 days prior to Day 1, or planning to use during the study, of any CYP3A sensitive substrates, (excluding opioids), including but not limited to alfentanil, avanafil, budeso
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method