A Study of the Effect of IW-1701, a Stimulator of Soluble Guanylate Cyclase (sGC), on Patients With Sickle Cell Disease (SCD)
- Conditions
- Stable Sickle Cell Disease (SCD)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
- EUCTR2019-001899-11-GB
- Lead Sponsor
- Cyclerion Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 88
1. Patient has provided written consent before any study-specific procedures are performed; for patients <18 years of age, parental permission and child assent will be obtained.
2. Patient is ambulatory male or female 16 to 70 years of age at the Screening Visit.
3. Patient has sickle cell disease (SCD), including HbSS, HbSC, HbSß0-thalassemia, or HbSß+-thalassemia, documented in their medical history by hemoglobin electrophoresis or genotyping.
4. If receiving hydroxyurea (HU), erythropoietin, L-glutamine, or prophylactic oral antibiotics, patient has had no change in regimen(s) (ie, drug and dose) for at least 8 weeks before the Randomization Visit and has no plans to change regimen(s) during the study. If receiving HU, patient must have been prescribed HU for at least 6 months prior to the Randomization Visit. (Note: Patient is not required to be taking medication[s] for SCD.)
Should the patient begin any new chronic treatment/therapy for SCD during the study or alter any current treatment/therapy for SCD during the study, the Sponsor Medical Monitor must be informed.
5. If receiving chronic medication(s) for hypertension, patient has had no change in regimen(s) (ie, drug and dose) for at least 8 weeks before the Randomization Visit and has no plans to change regimen(s) during the study.
6. Per medical history and/or patient recall, patient has had at least 1 and no more than 10 sickle cell-related pain crises in the 12 months before the Screening Visit and none occurring in the 4 weeks before the Randomization Visit.
For assessing study eligibility, an SCD-related pain crisis is defined as an acute episode of new-onset pain that lasts =2 hours with no medically determined cause other than a vaso-occlusive event and requires presentation to a medical facility (eg, acute care setting,
Emergency Department, urgent care clinic) and treatment with oral or parenteral opioids, parenteral nonsteroidal anti-inflammatory drugs, or other analgesics, prescribed by a healthcare provider.
7. Patient has clinically acceptable (per Investigator discretion) electrocardiogram (ECG) with QT interval corrected using Fridericia’s formula (QTcF interval) <500 ms at the Screening Visit.
8. Patient has seated systolic blood pressure (BP) from 90 to 160 mmHg at the Screening Visit. (Note: BP for eligibility will be the average of 3 measurements obtained with an appropriately sized cuff at 2-minute intervals after the patient has been sitting quietly for =5 minutes.)
9. Female patient must be postmenopausal (no menses for =12 consecutive months) or surgically sterile (ie, bilateral oophorectomy, hysterectomy, or tubal sterilization [tie, clip, band, or burn]); must agree to completely abstain from heterosexual intercourse; or, if heterosexually active, must agree to use 1 of the following methods of birth control from the date she signs the informed consent form (ICF) until 90 days after the final dose of study drug:
- Progesterone implant and/or an intrauterine device (IUD)
- Combination of 2 highly effective birth control methods (eg, diaphragm with spermicide plus a condom, condom with spermicide plus a diaphragm or cervical cap, hormonal contraceptive [eg, oral and transdermal patch] plus a barrier method, or partner with vasectomy [conducted =60 days before the Screening Visit or confirmed via sperm analysis] plus a hormone or barrier method).
10. Male patient must be surgically sterile by vasectomy (conducted =60 days before the Screening Visit or con
1. Patient requires a program of prescheduled, regularly administered chronic blood transfusion therapy, has received a transfusion in the 8 weeks before the Randomization Visit, and/or is scheduled to receive a transfusion during the study.
2. Patient has been hospitalized for an SCD-related complication in the 4 weeks before the Randomization Visit.
3. Patient is planning to undergo major surgery during the trial or has undergone surgery within 4 weeks of the Screening Visit, other than minor dermatologic procedures.
4. Patient has used oral or parenteral corticosteroids in the 8 weeks before the Randomization visit. Note: Transient use for =2 days may be acceptable; consult the Medical Monitor for confirmation.
5. Patient has taken opioid(s) >200 morphine mg equivalent/day within the 4 weeks before the Randomization Visit.
6. Patient is taking aspirin =325 mg daily, any P2Y12 inhibitor, any anticoagulant medication, specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of PDE5 (including dipyridamole and theophylline), any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide donors in any form.
Patient is taking moderate or strong cytochrome P450 3A (CYP3A) inhibitors or inducers.
These medications are prohibited from the Run-in Visit (which may occur from Day -14 to Day -17) through the duration of the study.
See Appendix 1 of the study protocol for a list of prohibited medications, supplements, and foods.
7. Patient uses or requires the use of fentanyl.
8. Patient has any of the following clinical laboratory values at the Screening Visit:
a. Hemoglobin =6 g/dL
b. Platelets =100×109/L
c. Absolute neutrophils =1.5×109/L
d. Alanine aminotransferase >1.5×the upper limit of normal (ULN) as defined by laboratory
e. Direct bilirubin >3×ULN as defined by laboratory
f. Creatinine clearance <30 mL/minute/1.73 m2 by the Modification of Diet in Renal Disease equation
g. Prothrombin time and/or aPTT >1.5×ULN and considered clinically significant by the Investigator, and/or INR>1.5
9. Patient has oxygen saturation =90% by pulse oximetry on room air at the Screening Visit and/or at the Randomization Visit.
10. Patient has had inpatient hospitalization for alcoholism or drug addiction in the 12 months before the Screening Visit or is positive for any the following at the Screening Visit unless legally prescribed: Amphetamines, Benzodiazepines, Opiates, Propoxyphene, Barbiturates, Cocaine, Phencyclidine
11. Patient has major concurrent illness or medical condition that in the opinion of the Investigator would preclude participation in a clinical study, including but not limited to:
a. Uncontrolled significant cardiovascular disease or clinically significant cardiac arrhythmia as assessed by the Investigator
b. Serious event such as stroke or transient ischemic attack =12 months before Randomization, or deep venous thrombosis or pulmonary embolism =6 months before Randomization
c. History of platelet dysfunction, hemophilia, von Willebrand disease, coagulation disorder, other bleeding diathesis condition(s), or significant, nontraumatic bleeding episodes, such as from a gastrointestinal source, even if patient has normal complete blood count, prothrombin time, and activated partial thromboplastin time at the screening Visit
d. Known severe central nervous system vasculopathy (eg, Moyamoya disease, arteriovenous malformations)
e. Interstitial lung disease requiring continuous oxygen
f. Kn
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