Clinical study to review how safe and how well tolerated IMR-687 is in subjects with Beta Thalassemia
- Conditions
- ß-thalassemiaMedDRA version: 20.1Level: LLTClassification code 10054660Term: Thalassemia betaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-002989-12-FR
- 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
- 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 hemoglobine (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 units 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 units 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 of the protocol).
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. Detailed information is available in the protocol.
9. Subjects receiving hydroxyurea must have received it continuously for at least 6 months prior to signing the ICF, and must have been on a stable dose for at least 3 months prior to signing the ICF, with no anticipated need for dose adjustments during the study including the screening period, in the opinion of the investigator.
10. For NTDT subjects only: Subjects must have mean baseline Hb =10.0 g/dL, based on a minimum of 2 measurements =1 week apart within 4 weeks prior to randomization; Hb values within 21 days post-transfusion will be excluded.
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 118
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
Subjects meeting any of the following criteria must be excluded from the study:
1. Any significant medical condition, lab 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., HbH) or HbS/ ß-thalassemia.
4. BMI <17.0 kg/m2 or a total body weight <45 kg; or BMI >35 kg/m2.
5. Subjects with known active HAV, HBV, or HCV, 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 × 10^9/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 proteinuria (>3 g/L).
15. Subjects who have received chronic systemic glucocorticoid
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