Clinical trial NCT03285178: A Study of the Effect of IW-1701 (Olinciguat), a Stimulator of Soluble Guanylate Cyclase (sGC), on Patients With Sickle Cell Disease (SCD)
Official title: A Randomized, Placebo-controlled, Phase 2 Study to Evaluate the Safety and Pharmacodynamics of Once-daily Oral IW-1701 in Patients With Stable Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease
SCD
Olinciguat
IW-1701
Lead sponsor: Cyclerion Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-09-15
Enrollment: 88
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: INCLUSION CRITERIA

1. Patient is ambulatory male or female 16 to 70 years of age at the Screening Visit.
2. Patient has SCD, including homozygous hemoglobin S (HbSS), hemoglobin SC disease (HbSC), heterozygous hemoglobin S-beta zero (HbSβ0)-thalassemia, or heterozygous hemoglobin S-beta plus (HbSβ+)-thalassemia, documented in their medical history.
3. If patient is on medication(s) for SCD, such as hydroxyurea (HU), are on a stable regimen.
4. 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.
5. Patient completes daily eDiary entries for at least 10 days during the last 14 days of the Run in Period as assessed at the Randomization Visit.
6. Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 90 days after the final dose of study drug.
7. Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception and agree to refrain from sperm donation from the Screening Visit through 90 days after the final dose of study drug.

EXCLUSION CRITERIA

1. Patient requires a program of prescheduled, regularly administered chronic blood transfusion therapy.
2. Patient has been hospitalized for an SCD-related complication in the 4 weeks before the Randomization Visit.
3. Patient has taken opioid(s) \>200 morphine mg equivalent/day within the 4 weeks before the Randomization Visit.
4. Patient is taking aspirin ≥325 mg daily, P2Y12 inhibitors, any anticoagulant medication, specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of phosphodiesterase 5 (PDE5), moderate or strong cytochrome P450 3A (CYP3A) inhibitors, any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide donors in any form.
5. Patient has major concurrent illness or medical condition that in the opinion of the Investigator would preclude participation in a clinical study.

NOTE: Other inclusion and exclusion criteria apply, per protocol

Primary outcomes:
measure: Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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.
measure: Double-Blind Treatment: Number of TEAE Events
timeFrame: 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.
measure: Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity
timeFrame: 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.
measure: Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Washington
country: United States
facility: MedStar Health Research Institute, MedStar Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: Howard University Center for Sickle Cell Disease
state: District of Columbia
city: Aventura
country: United States
facility: Innovative Medical Research of South Florida, Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: Century Clinical Research, Inc.
state: Florida
city: Hollywood
country: United States
facility: Foundation for Sickle Cell Disease Research
state: Florida
city: Orlando
country: United States
facility: Omega Research Maitland, LLC
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Flossmoor
country: United States
facility: Healthcare Research Network II, LLC
state: Illinois
city: Lake Charles
country: United States
facility: Clinical Trials of SWLA, LLC
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine Children's Center
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan-Detroit
state: Michigan
city: Hazelwood
country: United States
facility: Healthcare Research Network
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center, Pediatric Hematology and Oncology
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Greenville
country: United States
facility: East Carolina University - Leo W. Jenkins Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University Brody School of Medicine, Department of Pediatrics, Division of Pediatric Hematology
state: North Carolina
city: Tulsa
country: United States
facility: Lynn Institute of Tulsa
state: Oklahoma
city: Jenkintown
country: United States
facility: The Clinical Trial Center LLC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Hillman Cancer Center
state: Pennsylvania
city: Baytown
country: United States
facility: Accurate Clinical Research
state: Texas
city: Houston
country: United States
facility: "UT Health Clinical Research Unit Center for Clinical and Translational Sciences
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Center UT Health San Antonio
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University - Clinical Research Unit
state: Virginia
city: Wauwatosa
country: United States
facility: Blood Center of Wisconsin (BCW)
state: Wisconsin
city: Sidon
country: Lebanon
facility: Hammoud Hospital University Medical Center
city: Tripoli
country: Lebanon
facility: Nini Hospital
city: London
country: United Kingdom
facility: Royal London Hospital
city: London
country: United Kingdom
facility: Whittington Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust - Evelina London Childrens Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
References: