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)

• ClinicalTrials.gov Identifier: NCT03285178
• Recruitment Status: Completed
• First Posted: September 15, 2017
• Last Update Posted: July 22, 2021
• Sponsor: Cyclerion Therapeutics
• Information provided by (Responsible Party): Cyclerion Therapeutics

Tracking Information

• First Submitted Date: September 8, 2017
• First Posted Date: September 15, 2017
• Last Update Posted Date: July 22, 2021
• Actual Study Start Date: December 22, 2017
• Actual Primary Completion Date: July 22, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2020)

• Incidence (number and percentage of patients) and frequency (number of events) of treatment-emergent adverse events (TEAE). [ Time Frame: From first dose of study treatment through 7 days of last dose. ]
• Incidence of treatment-emergent adverse events (TEAE) by severity [ Time Frame: From first dose of treatment through 7 days of last dose. ]
• Incidence of study drug related treatment-emergent adverse events (TEAE) [ Time Frame: From first dose of treatment through 7 days of last dose. ]

• Original Primary Outcome Measures (submitted: September 13, 2017): Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Study Drug-Related TEAEs [ Time Frame: From first dose of study treatment through Follow-Up Visit (Day 113 -3/+7 days) ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sickle Cell Disease

Intervention

• Drug: IW-1701
  Oral Tablet
  Other Name: Olinciguat
• Drug: Placebo
  Oral Tablet

Study Arms

• Experimental: IW-1701 (Olinciguat) Low Dose
  Intervention: Drug: IW-1701
• Experimental: IW-1701 (Olinciguat) Medium Dose
  Intervention: Drug: IW-1701
• Experimental: IW-1701 (Olinciguat) High Dose
  Intervention: Drug: IW-1701
• Experimental: IW-1701 (Olinciguat) Higher Dose
  Intervention: Drug: IW-1701
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 28, 2020): 70
• Original Estimated Enrollment (submitted: September 13, 2017): 88
• Actual Study Completion Date: July 22, 2020
• Actual Primary Completion Date: July 22, 2020 (Final data collection date for primary outcome measure)

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 HbSS, HbSC, HbSβ0-thalassemia, or 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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Lebanon, United Kingdom, United States

Administrative Information

• NCT Number: NCT03285178
• Other Study ID Numbers: C1701-202
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cyclerion Therapeutics
• Original Responsible Party: Ironwood Pharmaceuticals, Inc.
• Current Study Sponsor: Cyclerion Therapeutics
• Original Study Sponsor: Ironwood Pharmaceuticals, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Cyclerion Therapeutics
• Verification Date: July 2021