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

Cyclerion Therapeutics88 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Sickle Cell Disease

Interventions

IW-1701DRUG

Oral Tablet

PlaceboDRUG

Oral Tablet

Eligibility

Sex: ALLMin age: 16 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (37)

Outcomes

Primary Outcomes

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.

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.

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.

Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity

Data from ClinicalTrials.gov

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Children's Hospital of Orange County

Orange, California, United States

MedStar Health Research Institute, MedStar Washington Hospital Center

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

Howard University Center for Sickle Cell Disease

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

Innovative Medical Research of South Florida, Inc.

Aventura, Florida, United States

Century Clinical Research, Inc.

Fort Lauderdale, Florida, United States

Foundation for Sickle Cell Disease Research

Hollywood, Florida, United States

Omega Research Maitland, LLC

Orlando, Florida, United States

Grady Memorial Hospital

Atlanta, Georgia, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

University of Illinois at Chicago

Chicago, Illinois, United States

...and 27 more locations