A Study of the Effect of IW-1701 (Olinciguat), a Stimulator of Soluble Guanylate Cyclase (sGC), on Patients With Sickle Cell Disease (SCD)
- Registration Number
- NCT03285178
- Lead Sponsor
- Cyclerion Therapeutics
- Brief Summary
The primary objective of the 1701-202 STRONG SCD study is to evaluate the safety and tolerability of different dose levels of IW-1701 compared with placebo when administered daily for approximately 12 weeks to patients with stable SCD. Exploratory objectives include evaluation of pharmacokinetic (PK) as well as evaluation of the effect of IW-1701 on symptoms of SCD, health-related quality of life, and biomarkers of pharmacodynamic (PD) activity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 88
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IW-1701 (Olinciguat) 6 mg IW-1701 After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 3 mg olinciguat QD Week 1 and 6 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3. Placebo Placebo After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received placebo treatment QD for 12 weeks. IW-1701 (Olinciguat) 2 mg IW-1701 After a single-blind treatment with placebo once daily (QD) for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 1 mg olinciguat QD Week 1 and 2 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3. IW-1701 (Olinciguat) 18 mg IW-1701 After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 6 mg olinciguat QD Days 1-7, 12 mg olinciguat QD Weeks 1-3, and 18 mg olinciguat QD Weeks 4-12 under protocol Amendment 4 and later. IW-1701 (Olinciguat) 4 mg IW-1701 After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 2 mg olinciguat QD Week 1 and 4 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.
- Primary Outcome Measures
Name Time Method Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups. An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.
Double-Blind Treatment: Number of TEAE Events First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups. An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.
Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups. An adverse event (AE) is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. Adverse Events of special interest (AESIs) included symptomatic or Grade ≥2 hypotensive events and/or tachycardia AEs, bleeding events, pulmonary edema, and bone-related events, including fractures.
Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups. An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the most severe occurrence was counted.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (37)
Hammoud Hospital University Medical Center
🇱🇧Sidon, Lebanon
Foundation for Sickle Cell Disease Research
🇺🇸Hollywood, Florida, United States
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
MedStar Health Research Institute, MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Century Clinical Research, Inc.
🇺🇸Fort Lauderdale, Florida, United States
Atlanta Center for Medical Research
🇺🇸Atlanta, Georgia, United States
Healthcare Research Network II, LLC
🇺🇸Flossmoor, Illinois, United States
New York Medical College
🇺🇸Valhalla, New York, United States
East Carolina University - Leo W. Jenkins Cancer Center
🇺🇸Greenville, North Carolina, United States
Blood Center of Wisconsin (BCW)
🇺🇸Wauwatosa, Wisconsin, United States
University of Pittsburgh Medical Center Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Accurate Clinical Research
🇺🇸Baytown, Texas, United States
"UT Health Clinical Research Unit Center for Clinical and Translational Sciences
🇺🇸Houston, Texas, United States
Virginia Commonwealth University - Clinical Research Unit
🇺🇸Richmond, Virginia, United States
Omega Research Maitland, LLC
🇺🇸Orlando, Florida, United States
Children's Hospital of Michigan-Detroit
🇺🇸Detroit, Michigan, United States
Mays Cancer Center UT Health San Antonio
🇺🇸San Antonio, Texas, United States
Innovative Medical Research of South Florida, Inc.
🇺🇸Aventura, Florida, United States
Johns Hopkins School of Medicine Children's Center
🇺🇸Baltimore, Maryland, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Clinical Trials of SWLA, LLC
🇺🇸Lake Charles, Louisiana, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Healthcare Research Network
🇺🇸Hazelwood, Missouri, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
Hackensack University Medical Center, Pediatric Hematology and Oncology
🇺🇸Hackensack, New Jersey, United States
East Carolina University Brody School of Medicine, Department of Pediatrics, Division of Pediatric Hematology
🇺🇸Greenville, North Carolina, United States
Lynn Institute of Tulsa
🇺🇸Tulsa, Oklahoma, United States
The Clinical Trial Center LLC
🇺🇸Jenkintown, Pennsylvania, United States
Whittington Hospital
🇬🇧London, United Kingdom
Nini Hospital
🇱🇧Tripoli, Lebanon
Royal London Hospital
🇬🇧London, United Kingdom
Guys and St Thomas NHS Foundation Trust - Evelina London Childrens Hospital
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Howard University Center for Sickle Cell Disease
🇺🇸Washington, District of Columbia, United States
Guy's Hospital
🇬🇧London, United Kingdom