| 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 <10.5 g/dL.
5. Absolute reticulocyte count ≥80 × 109
/L.
6. Subjects receiving HU 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.
7. 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 |
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) <45 mL/min as calculated by the equation from the
Modification of Diet in Renal Disease Study using creatinine, age, sex, and ethnicity.
7. Alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal.
8. Body mass index (BMI) <17.0 kg/m2 and a total body weight <45 kg; or a 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)
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 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.
17. Poorly controlled diabetes mellitus as defined by 1) fructosamine levels of >340 µmol/L within
12 weeks prior to randomization (Day 1); 2) short-term hyperglycemia leading to
hyperosmolar or ketoacidotic crisis; and/or 3) history of diabetic cardiovascular complications.
IMR-SCD-301 Protocol, v. 3.0
29 JAN 2020 Proprietary and Confidential Page 10 of 80
18. Subject has received chronic systemic glucocorticoids within 12 weeks prior to randomization
(≥5 mg/day). Physiologic replacement therapy for adrenal insufficiency is allowed.
19. Any clinically significant bacterial, fungal, parasitic, or viral infection requiring antibiotic
therapy should delay screening/randomization (Day 1) until the course of antibiotic therapy has
been completed. This includes, but is not limited to, long-term tuberculosis treatment.
20. 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).
21. Prior exposure to IMR-687.
22. A history of use of crizanlizumab or voxelotor within 6 months prior to signing the ICF.
23. Consumption/use of the following drugs or other substances within the specified time periods
before randomization or plans to consume/use at any time during the study. If there is any
question as to whether a substance is permitted, please review the product labeling (if
applicable) and consult the medical monitor and/or sponsor.
a. PDE5 inhibitors (including but not limited to sildenafil, tadalafil, and vardenafil) within
7 days prior to randomization (Day 1) or plans to use during the study.
b. Grapefruit, grapefruit juice, grapefruit products, or herbal supplements with CYP-altering
abilities within 1 week prior to randomization (Day 1) or plans to consume during the
study.
c. CYP3A-sensitive substrates, including the opioids fentanyl and alfentanil, or moderate to
strong CYP3A inhibitors or inducers within 28 days prior to randomization (Day 1) or
plans to use during the study
d. Any drugs or substances known to be substrates or inhibitors of P-glycoprotein (P-gp) or
breast cancer resistance protein (BCRP) within 28 days prior to randomization (Day 1) or
plans to use during the study.
24. Receipt of erythropoietin or other hematopoietic growth factor treatment within 3 months of
signing the ICF or anticipated need for such agents during the study.
25. Prior gene therapy.
26. 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.
27. Other prior or ongoing medical condition, physical findings, or laboratory abnormality that, in
the investigator’s opinion, could adversely affect the safety of the subject, make it unlikely that
the course of treatment or follow-up would be completed, or impair the assessment of study
results (e.g., a history of drug or alcohol abuse within the past 1 year, as judged by the
investigator). |
Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) |
18 Year(s) |
65 Year(s) |
Both |