A Study of the Effect of IW-1701 (Olinciguat), a Stimulator of Soluble Guanylate Cyclase (sGC), on Patients With Sickle Cell Disease (SCD)

Sickle Cell Disease Clinical Trial

— STRONG 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03285178
• Other study ID #: C1701-202
• Status: Completed
• Phase: Phase 2
• Start date: December 22, 2017
• Est. completion date: July 22, 2020

Study information

• Verified date: July 2023
• Source: Cyclerion Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: July 22, 2020
• Est. primary completion date: July 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

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 (HbSß0)-thalassemia, or heterozygous hemoglobin S-beta plus (HbSß+)-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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• IW-1701
Oral Tablet
• Placebo
Oral Tablet

Locations

Country	Name	City	State
Lebanon	Hammoud Hospital University Medical Center	Sidon
Lebanon	Nini Hospital	Tripoli
United Kingdom	Guy's Hospital	London
United Kingdom	Guys and St Thomas NHS Foundation Trust - Evelina London Childrens Hospital	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal London Hospital	London
United Kingdom	Whittington Hospital	London
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia
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 Maryland Medical Center	Baltimore	Maryland
United States	Accurate Clinical Research	Baytown	Texas
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Children's Hospital of Michigan-Detroit	Detroit	Michigan
United States	Healthcare Research Network II, LLC	Flossmoor	Illinois
United States	Century Clinical Research, Inc.	Fort Lauderdale	Florida
United States	East Carolina University - Leo W. Jenkins Cancer Center	Greenville	North Carolina
United States	East Carolina University Brody School of Medicine, Department of Pediatrics, Division of Pediatric Hematology	Greenville	North Carolina
United States	Hackensack University Medical Center, Pediatric Hematology and Oncology	Hackensack	New Jersey
United States	Healthcare Research Network	Hazelwood	Missouri
United States	Foundation for Sickle Cell Disease Research	Hollywood	Florida
United States	"UT Health Clinical Research Unit Center for Clinical and Translational Sciences	Houston	Texas
United States	The Clinical Trial Center LLC	Jenkintown	Pennsylvania
United States	Clinical Trials of SWLA, LLC	Lake Charles	Louisiana
United States	Children's Hospital of Orange County	Orange	California
United States	Omega Research Maitland, LLC	Orlando	Florida
United States	University of Pittsburgh Medical Center Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University - Clinical Research Unit	Richmond	Virginia
United States	Mays Cancer Center UT Health San Antonio	San Antonio	Texas
United States	Lynn Institute of Tulsa	Tulsa	Oklahoma
United States	New York Medical College	Valhalla	New York
United States	Howard University Center for Sickle Cell Disease	Washington	District of Columbia
United States	MedStar Health Research Institute, MedStar Washington Hospital Center	Washington	District of Columbia
United States	Blood Center of Wisconsin (BCW)	Wauwatosa	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Cyclerion Therapeutics

Countries where clinical trial is conducted

United States,  Lebanon,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	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.
Primary	Double-Blind Treatment: Number of TEAE Events	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.	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.
Primary	Double-Blind Treatment: Number of Participants With =1 TEAE, by Maximum Severity	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.	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.
Primary	Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs	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.	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.