A Phase 2 Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia
- Conditions
- Reduced Hb in red blood cells (RBCs), decreased RBC production, and anemia due to reduced or absent synthesis of the ß chain of hemoglobin (Hb) and mutations in the hemoglobin beta (HBB) gene in subjects with ß-thalassemia.Thalassemia
- Registration Number
- LBCTR2020093402
- Lead Sponsor
- IMARA, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 120
Subjects must meet all of the following inclusion criteria to be eligible for the study:
1. Subjects must understand and voluntarily provide informed consent and sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted. Although RBC transfusions and associated Hb laboratory measurements 12 weeks prior to the
Screening visit are not study related, the ICF will specifically request subject consent to collect these data.
2. Subjects must be =18 to =65 years of age at the time of signing the ICF.
3. Subjects must have documented diagnosis of ß-thalassemia or HbE/ß-thalassemia. Concomitant single alpha gene deletion, duplication, or triplication is allowed.
4. For TDT subjects only: Subjects must be regularly transfused, defined as >3 to 10 RBC units1 in the 12 weeks prior to screening and no transfusion-free period for =35 days during that period.
For NTDT subjects only: Subjects must be transfusion independent, defined as 0 to =3 units1 of RBCs received during the 12-week period prior to randomization, must not be on a regular transfusion program, must be RBC transfusion-free for at least = 4 weeks prior to randomization, and must not be scheduled to start a regular hematopoietic stem cell transplantation within 9 months.
5. Subjects must have documentation of dates of transfusions and the number of all RBC units within the 12 weeks prior to Screening.
6. Subjects must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.
7. Subjects must have Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1 (Appendix 1).
8. Female subjects must not be pregnant, not be breast feeding, and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner. Male or female subjects must meet at least one of the following criteria:
• A female subject who is not of reproductive potential is eligible without requiring the use of contraception. A female subject who is not of reproductive potential is defined as one who: (1) has reached natural menopause (defined as 12 months of spontaneousamenorrhea without an alternative medical cause, and can be confirmed with serum follicle-stimulating hormone levels in the postmenopausal range as determined by the
central 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 (e.g., anorexia nervosa).
• A female of reproductive potential must have 2 negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, at the end of treatment visit, and at the end of study visit. This applies even if the subject practices true abstinence from heterosexual contact.
• A male subject who is not of reproductive potential is eligible without requiring the use of contraception. A male subject 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 subject who is of reproductive potential agrees to remain trul
Subjects meeting any of the following criteria must be excluded from the study:
1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study, including the presence of laboratory abnormalities that may place the subject at unacceptable risk if he/she were to participate in the study.
2. Any situation or condition that confounds the ability to interpret data from the study (e.g., subjects also receiving RBC transfusions at centers not able to obtain laboratory samples for central processing).
3. Diagnosis of a-thalassemia (e.g., hemoglobin H [HbH]) or hemoglobin S (HbS)/ ß-thalassemia.
4. Body mass index (BMI) <17.0 kg/m² or a total body weight <45 kg; or BMI >35 kg/m².
5. 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).
6. Stroke requiring medical intervention =24 weeks prior to randomization.
7. 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 are permitted. Anti-coagulant therapies for prophylaxis of venous thromboembolism, including pulmonary emboli including when undergoing surgery or high-risk procedures, are allowed if low molecular weight heparins are used in the peri-operative period. Aspirin use is allowed before and during the study.
8. Treatment with an investigational drug or device or participation in an investigational drug or device study =28 days prior to randomization.
9. Platelet count >1000 × 10?/L.
10. Subjects on iron chelation therapy (ICT) at the time of ICF signing must have initiated the treatment with ICT at least 24 weeks before the predicted randomization date. ICT can be initiated at any time during treatment and should be used according to the label.
11. Subjects who have had treatment with erythropoietin-stimulating agents =24 weeks prior to randomization.
12. Uncontrolled hypertension as defined by systolic BP =160 mm Hg or diastolic BP =100 mm Hg, medical intervention indicated, and more than one drug or more intensive therapy than previously used indicated.
13. Poorly controlled diabetes mellitus as defined by 1) fructosamine levels of >340 µmol/L within 12 weeks prior to randomization; 2) short term hyperglycemia leading to hyperosmolar or ketoacidotic crisis; and/or 3) history of diabetic cardiovascular complications.
14. Subjects who have major organ damage, including:
a. Liver disease with ALT or AST >3× ULN, direct bilirubin >2× ULN, or history/evidence of cirrhosis, as well as presence of masses/tumor.
b. Heart disease, heart failure as classified by the New York Heart Association
classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction within 6 months of randomization, or significant cardiac iron T2* <15 ms, or left ventricular ejection fraction <56%.
c. Severe lung disease, including pulmonary fibrosis or pulmonary hypertension, i.e., =Grade 3 NCI CTCAE version 5.0.
d. Estimated glomerular filtration rate <45 mL/min/1.73 m2 (per Modification of Diet in Renal Disease formula).
e. Nephrotic range proteinu
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method