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

NCT03285178 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: C1701-202
• Study Type: interventional
• Target: 88
• Locations: 3 countries
• Sites: 37

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.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; SCD; Olinciguat; IW-1701

Outcome Measures

Primary Outcomes (4)

• 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.

• 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.

• 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.

• 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.

Study Arms (5)

IW-1701 (Olinciguat) 2 mg

EXPERIMENTAL

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.

Drug: IW-1701

IW-1701 (Olinciguat) 4 mg

EXPERIMENTAL

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.

Drug: IW-1701

IW-1701 (Olinciguat) 6 mg

EXPERIMENTAL

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.

Drug: IW-1701

IW-1701 (Olinciguat) 18 mg

EXPERIMENTAL

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.

Drug: IW-1701

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

IW-1701 DRUG

Oral Tablet

Also known as: Olinciguat

IW-1701 (Olinciguat) 18 mg; IW-1701 (Olinciguat) 2 mg; IW-1701 (Olinciguat) 4 mg; IW-1701 (Olinciguat) 6 mg

Placebo DRUG

Oral Tablet

Placebo

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is ambulatory male or female 16 to 70 years of age at the Screening Visit.
• 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.
• If patient is on medication(s) for SCD, such as hydroxyurea (HU), are on a stable regimen.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• Patient requires a program of prescheduled, regularly administered chronic blood transfusion therapy.
• Patient has been hospitalized for an SCD-related complication in the 4 weeks before the Randomization Visit.
• Patient has taken opioid(s) \>200 morphine mg equivalent/day within the 4 weeks before the Randomization Visit.
• 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.
• Patient has major concurrent illness or medical condition that in the opinion of the Investigator would preclude participation in a clinical study.

Sponsors & Collaborators

• Cyclerion Therapeutics: lead

Study Sites (37)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

MedStar Health Research Institute, MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Howard University Center for Sickle Cell Disease

Washington D.C., District of Columbia, 20060, United States

Location

Innovative Medical Research of South Florida, Inc.

Aventura, Florida, 33180, United States

Location

Century Clinical Research, Inc.

Fort Lauderdale, Florida, 32117, United States

Location

Foundation for Sickle Cell Disease Research

Hollywood, Florida, 33021, United States

Location

Omega Research Maitland, LLC

Orlando, Florida, 32810, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Healthcare Research Network II, LLC

Flossmoor, Illinois, 60422, United States

Location

Clinical Trials of SWLA, LLC

Lake Charles, Louisiana, 70601, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins School of Medicine Children's Center

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Michigan-Detroit

Detroit, Michigan, 33021, United States

Location

Healthcare Research Network

Hazelwood, Missouri, 63042, United States

Location

Hackensack University Medical Center, Pediatric Hematology and Oncology

Hackensack, New Jersey, 07601, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

East Carolina University - Leo W. Jenkins Cancer Center

Greenville, North Carolina, 27834, United States

Location

East Carolina University Brody School of Medicine, Department of Pediatrics, Division of Pediatric Hematology

Greenville, North Carolina, 27834, United States

Location

Lynn Institute of Tulsa

Tulsa, Oklahoma, 74105, United States

Location

The Clinical Trial Center LLC

Jenkintown, Pennsylvania, 19046, United States

Location

University of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Accurate Clinical Research

Baytown, Texas, 77521, United States

Location

"UT Health Clinical Research Unit Center for Clinical and Translational Sciences

Houston, Texas, 77030, United States

Location

Mays Cancer Center UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University - Clinical Research Unit

Richmond, Virginia, 23298, United States

Location

Blood Center of Wisconsin (BCW)

Wauwatosa, Wisconsin, 53226, United States

Location

Hammoud Hospital University Medical Center

Sidon, Lebanon

Location

Nini Hospital

Tripoli, Lebanon

Location

Royal London Hospital

London, E1 2ES, United Kingdom

Location

Whittington Hospital

London, N19 5NF, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust - Evelina London Childrens Hospital

London, SE1 7EH, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Hammersmith Hospital

London, W12 0NN, United Kingdom

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Senior Medical Director
• Organization: Cyclerion Therapeutics, Inc.

info@cyclerion.com

1-857-327-8778

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2017
• First Posted: September 15, 2017
• Study Start: December 22, 2017
• Primary Completion: July 22, 2020
• Study Completion: July 22, 2020
• Last Updated: July 21, 2023
• Results First Posted: July 21, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (30); LE (2); GB (5)