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

July 19, 2023 updated by: Cyclerion Therapeutics

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

88

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Sidon, Lebanon
        • Hammoud Hospital University Medical Center
      • Tripoli, Lebanon
        • Nini Hospital
      • London, United Kingdom, SE1 9RT
        • Guy's Hospital
      • London, United Kingdom, W12 0NN
        • Hammersmith Hospital
      • London, United Kingdom, N19 5NF
        • Whittington Hospital
      • London, United Kingdom, E1 2ES
        • Royal London Hospital
      • London, United Kingdom, SE1 7EH
        • Guys and St Thomas NHS Foundation Trust - Evelina London Childrens Hospital
    • California
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • MedStar Health Research Institute, MedStar Washington Hospital Center
      • Washington, District of Columbia, United States, 20060
        • Howard University Center for Sickle Cell Disease
    • Florida
      • Aventura, Florida, United States, 33180
        • Innovative Medical Research of South Florida, Inc.
      • Fort Lauderdale, Florida, United States, 32117
        • Century Clinical Research, Inc.
      • Hollywood, Florida, United States, 33021
        • Foundation for Sickle Cell Disease Research
      • Orlando, Florida, United States, 32810
        • Omega Research Maitland, LLC
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Grady Memorial Hospital
      • Atlanta, Georgia, United States, 30331
        • Atlanta Center for Medical Research
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago
      • Flossmoor, Illinois, United States, 60422
        • Healthcare Research Network II, LLC
    • Louisiana
      • Lake Charles, Louisiana, United States, 70601
        • Clinical Trials of SWLA, LLC
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins School of Medicine Children's Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Michigan
      • Detroit, Michigan, United States, 33021
        • Children's Hospital of Michigan-Detroit
    • Missouri
      • Hazelwood, Missouri, United States, 63042
        • Healthcare Research Network
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center, Pediatric Hematology and Oncology
    • New York
      • Bronx, New York, United States, 10461
        • Jacobi Medical Center
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • East Carolina University - Leo W. Jenkins Cancer Center
      • Greenville, North Carolina, United States, 27834
        • East Carolina University Brody School of Medicine, Department of Pediatrics, Division of Pediatric Hematology
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74105
        • Lynn Institute of Tulsa
    • Pennsylvania
      • Jenkintown, Pennsylvania, United States, 19046
        • The Clinical Trial Center LLC
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center Hillman Cancer Center
    • Texas
      • Baytown, Texas, United States, 77521
        • Accurate Clinical Research
      • Houston, Texas, United States, 77030
        • "UT Health Clinical Research Unit Center for Clinical and Translational Sciences
      • San Antonio, Texas, United States, 78229
        • Mays Cancer Center UT Health San Antonio
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University - Clinical Research Unit
    • Wisconsin
      • Wauwatosa, Wisconsin, United States, 53226
        • Blood Center of Wisconsin (BCW)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IW-1701 (Olinciguat) 2 mg
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.
Oral Tablet
Other Names:
  • Olinciguat
Experimental: IW-1701 (Olinciguat) 4 mg
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.
Oral Tablet
Other Names:
  • Olinciguat
Experimental: IW-1701 (Olinciguat) 6 mg
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.
Oral Tablet
Other Names:
  • Olinciguat
Experimental: IW-1701 (Olinciguat) 18 mg
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.
Oral Tablet
Other Names:
  • Olinciguat
Placebo Comparator: 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.
Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 22, 2017

Primary Completion (Actual)

July 22, 2020

Study Completion (Actual)

July 22, 2020

Study Registration Dates

First Submitted

September 8, 2017

First Submitted That Met QC Criteria

September 13, 2017

First Posted (Actual)

September 15, 2017

Study Record Updates

Last Update Posted (Actual)

July 21, 2023

Last Update Submitted That Met QC Criteria

July 19, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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