Sickle Cell DiseasePhase 2STRONG SCDNCT03285178

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

A Phase 2 study testing IW-1701 in people with Sickle Cell Disease, run by Cyclerion Therapeutics at 37 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 16 to 70 years
Conditions the study is for: Sickle Cell Disease
What is being tested?: IW-1701
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 88 participants
Where: 37 sitesin 3 countries
Study dates: 22 Dec 2017to 22 Jul 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 to 70 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.
NOTE: Other inclusion and exclusion criteria apply, per protocol

Trial locations and contacts

37 sites in 3 countries.

Country

City, postcode or hospital

37 sites in 3 countries

United States30 sites

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

Other trials in United States

United Kingdom5 sites

Royal London Hospital
London, E1 2ES
Whittington Hospital
London, N19 5NF
Guys and St Thomas NHS Foundation Trust - Evelina London Childrens Hospital
London, SE1 7EH
Guy's Hospital
London, SE1 9RT
Hammersmith Hospital
London, W12 0NN

Other trials in United Kingdom

Lebanon2 sites

Hammoud Hospital University Medical Center
Sidon
Nini Hospital
Tripoli

Other trials in Lebanon

About this study

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

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
Being tested: IW-1701, Placebo
Keywords: Sickle Cell Disease, SCD, Olinciguat, IW-1701
Medical subject headings: Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IW-1701Drug
Also called Olinciguat
Oral Tablet
PlaceboDrug
Oral Tablet

Study groups in NCT03285178
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Dec 201722 Jul 2020

First posted15 Sep 2017
Study start22 Dec 2017
Primary completion22 Jul 2020
Study completion22 Jul 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 88 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03285178
Sponsor's protocol ID: C1701-202
Acronym: STRONG SCD
Status last verified: Jul 2023
First submitted: 8 Sep 2017
Last updated: 21 Jul 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

All Sickle Cell Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03285178
Acronym / sponsor ID: STRONG SCD / C1701-202
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease, SCD, Olinciguat, IW-1701
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 88 participants (actual)
Lead sponsor: Cyclerion TherapeuticsIndustry (pharma, biotech, devices)
Study start: 22 Dec 2017 (actual)
Primary completion: 22 Jul 2020 (actual)
Study completion: 22 Jul 2020 (actual)
First posted: 15 Sep 2017 (actual)
Results: Posted 21 Jul 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
IW-1701 (Olinciguat) 2 mg	Experimental	Drug: IW-1701After 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.
IW-1701 (Olinciguat) 4 mg	Experimental	Drug: IW-1701After 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.
IW-1701 (Olinciguat) 6 mg	Experimental	Drug: IW-1701After 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.
IW-1701 (Olinciguat) 18 mg	Experimental	Drug: IW-1701After 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.
Placebo	Placebo comparator	Drug: PlaceboAfter 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.

Who may qualify

Ages: 16 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IW-1701Also: OlinciguatOral Tablet	Drug	IW-1701 (Olinciguat) 18 mg, IW-1701 (Olinciguat) 2 mg, IW-1701 (Olinciguat) 4 mg, IW-1701 (Olinciguat) 6 mg
PlaceboOral Tablet	Drug	Placebo

Primary outcome

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.
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.
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.
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.

Results and safety

Results posted to the registry on 21 Jul 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Single-Blind Run-in: Placebo	88	70
Double-Blind Treatment: Placebo 1	0	0
Double-Blind Treatment: Placebo 2	0	0
Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg	0	0
Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg	0	0
Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg	0	0
Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg	0	0

Primary outcome: 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.. Count of participants. Unit: Participants

Measure	Double-Blind Treatment: Placebo 1 n = 9	Double-Blind Treatment: Placebo 2 n = 8	Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg n = 8	Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg n = 8	Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg n = 11	Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg n = 24
Participants with >=1 TEAE	6	6	5	5	8	21
Participants with >=1 Grade 3-5 TEAE	2	2	2	3	4	7
Participants with >=1 Study Drug-Related TEAE	3	0	2	0	4	7
Participants with >=1 SAE	2	1	2	3	4	6
Participants with >=1 TEAE Leading to Study Drug Discontinuation	0	0	0	0	0	2
Participants with >=1 AESI	0	0	0	0	0	1

Population analysed: Safety Population: Randomized participants who received at least 1 dose of study drug

Primary outcome: Double-Blind Treatment: Number of TEAE Events

Measure	Placebo 1 n = 6	Placebo 2 n = 6	IW-1701 (Olinciguat) 2 mg n = 5	IW-1701 (Olinciguat) 4 mg n = 5	IW-1701 (Olinciguat) 6 mg n = 8	IW-1701 (Olinciguat) 18 mg n = 21
Value	26	29	36	30	39	101

Population analysed: Safety Population: Randomized participants who received at least 1 dose of study drug. Participants with \>=1 TEAE.

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

Measure	Placebo 1 n = 9	Placebo 2 n = 8	IW-1701 (Olinciguat) 2 mg n = 8	IW-1701 (Olinciguat) 4 mg n = 8	IW-1701 (Olinciguat) 6 mg n = 11	IW-1701 (Olinciguat) 18 mg n = 24
Participants with ≥1 TEAE: Any	6	6	5	5	8	21
Participants with ≥1 TEAE: Grade 1	0	4	0	2	2	6
Participants with ≥1 TEAE: Grade 2	4	0	3	0	2	8
Participants with ≥1 TEAE: Grade 3	2	2	2	3	4	7
Participants with ≥1 TEAE: Grade 4	0	0	0	0	0	0
Participants with ≥1 TEAE: Grade 5	0	0	0	0	0	0

Population analysed: Safety Population: Randomized participants who received at least 1 dose of study drug

Primary outcome: Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs

Measure	Placebo 1 n = 9	Placebo 2 n = 8	IW-1701 (Olinciguat) 2 mg n = 8	IW-1701 (Olinciguat) 4 mg n = 8	IW-1701 (Olinciguat) 6 mg n = 11	IW-1701 (Olinciguat) 18 mg n = 24
Value	3	0	2	0	4	7

Population analysed: Safety Population: Randomized participants who received at least 1 dose of study drug

Adverse events

Time frame: AEs during Single-blind Run-in Period were collected from first dose of Run-in placebo up to the first dose of randomized study drug, up to 17 days. AEs during the Double-Blind Period: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Single-Blind Run-in Period: Placebo	2 of 88 (2.3%)	18 of 88 (20.5%)	0 of 88
Double-Blind Treatment Period: Placebo 1	2 of 9 (22.2%)	6 of 9 (66.7%)	0 of 9
Double-Blind Treatment Period: Placebo 2	1 of 8 (12.5%)	6 of 8 (75%)	0 of 8
Double-Blind Treatment Period: IW-1701 (Olinciguat) 2 mg	2 of 8 (25%)	5 of 8 (62.5%)	0 of 8
Double-Blind Treatment Period: IW-1701 (Olinciguat) 4 mg	3 of 8 (37.5%)	5 of 8 (62.5%)	0 of 8
Double-Blind Treatment Period: IW-1701 (Olinciguat) 6 mg	4 of 11 (36.4%)	6 of 11 (54.5%)	0 of 11
Double-Blind Treatment Period: IW-1701 (Olinciguat) 18 mg	6 of 24 (25%)	20 of 24 (83.3%)	0 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

37 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IW-1701 in people with Sickle Cell Disease, run by Cyclerion Therapeutics at 37 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, United Kingdom, Lebanon. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03285178.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2023.