A Phase 2 Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia
- Conditions
- Beta Thalassemiainherited blood disorder10038158
- Registration Number
- NL-OMON54921
- Lead Sponsor
- IMARA, Inc.
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
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 prior to Screening 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 β-thalassemia or HbE/β-
thalassemia in their medical history. Concomitant alpha gene deletion,
duplication, or triplication is allowed.
4. For TDT subjects only: Subjects must be regularly transfused, defined as >3
to 10 pRBC units (one RBC unit refers to one bag of packed RBCs) in the 12
weeks prior to the Baseline (Day 1) visit 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 pRBCs received during the 12-week period prior to the Baseline
(Day 1) visit, 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 the dates of transfusion events and the
number of pRBC units per event within the 12 weeks prior to the Baseline (Day
1) visit.
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 or breastfeeding 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 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 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 succe
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)/
β 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 (<100 mg per day) is allowed before and during
the study.
8. Participated in another clinical study of an investigational agent (or
medical device) within 30 days or 5 half-lives of date of informed consent,
whichever is longer, or is currently participating in another study of an
investigational agent (or medical device).
9. Platelet count >1000 × 109/L.
10. For subjects on iron chelation therapy (ICT) at the time of ICF signing,
initiation of ICT less than 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, in the opinion of the investigator,
for example 1) Hb A1c >9.0% within 12 weeks prior to randomization (in the
medical history); 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 >3× ULN with
proportion of direct/total bilirubin >0.3; or history/evidence of cirrhosis,
liver transplant, or presence of clinically significant mass/tumor.
b. Heart disease, heart failure as classified by the New York Heart Association
classification 3 or higher, or significant arrhythmia requiring treatm
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Objective<br /><br>The primary objective of this study in both Population 1 (TDT) and Population 2<br /><br>(NTDT) is to assess the safety and tolerability of IMR-687 in adult subjects<br /><br>with β thalassemia.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Objectives<br /><br>The secondary objectives in Population 1 (TDT) subjects are:<br /><br>• To evaluate the effect of IMR-687 versus placebo on reduction in red blood<br /><br>cell (RBC) transfusion burden.<br /><br>• To evaluate the effect of IMR-687 versus placebo on the change in iron<br /><br>overload.<br /><br>• To characterize the pharmacokinetic (PK) profile of IMR-687 and collect data<br /><br>for population PK analysis.<br /><br>The secondary objectives in Population 2 (NTDT) subjects are:<br /><br>• To evaluate the effect of IMR-687 versus placebo on anemia (as defined by<br /><br>total hemoglobin [Hb]).<br /><br>• To evaluate the effect of IMR-687 versus placebo on fetal hemoglobin (HbF).<br /><br>• To evaluate the effect of IMR-687 versus placebo on the change in iron<br /><br>overload.<br /><br>• To characterize the PK profile of IMR-687 and collect data for population PK<br /><br>analysis</p><br>