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IW-1701

Phase 2

Sickle Cell Disease | Small molecule | Hematology |Cyclerion Therapeutics, Inc.|Last Updated: Jul 21, 2023

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment88

FDA Designations

No designations recorded

Clinical trial landscape

IW-1701 · 3 trials · 2 indications

Phase 2 1Phase 1 2
NCT03285178A Study of the Effect of IW-1701 (Olinciguat), a Stimulator of Soluble Guanylate Cyclase (sGC), on Patients With Sickle Cell Disease (SCD)Sickle Cell Disease
COMPLETED88 Analytics
PHASE2COMPLETED
A Study of the Effect of IW-1701 (Olinciguat), a Stimulator of Soluble Guanylate Cyclase (sGC), on Patients With Sickle Cell Disease (SCD)
Sickle Cell DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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
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
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
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.

Treatment Emergent Adverse Event
47 Days
Maximum observed plasma concentration [Cmax]
47 Days

Maximum observed Plasma Concentration

Area under the plasma concentration time curve during a dosing interval [AUC]
47 Days

Area under the plasma concentration time curve during a dosing interval

Time of maximum observed plasma concentration [Tmax]
47 Days

Time of maximum observed plasma concentration

Blood Pressure
47 Days
Assessment of the safety and tolerability of IW-1701 in healthy subjects via adverse events
From baseline up to 8 days

The primary objectives of this study are to assess the safety and tolerability of single ascending dosage levels of IW-1701 versus placebo in healthy subjects.

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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
IW-1701 (Olinciguat) 2 mgEXPERIMENTALAfter 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 mgEXPERIMENTALAfter 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 mgEXPERIMENTALAfter 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 mgEXPERIMENTALAfter 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.
PlaceboPLACEBO_COMPARATORAfter 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.
IW-1701EXPERIMENTALIW-1701 tablets administered orally in multiple ascending dose.
Matching Placebo for IW-1701PLACEBO_COMPARATORSingle Dose

Interventions

NameTypeDescription
IW-1701DRUGOral Tablet
PlaceboDRUGOral Tablet
Matching PlaceboDRUG -
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Eligibility Criteria

Age Range16 Years to 70 Years
SexALL
Healthy VolunteersNo
Study Sites37

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+...

Countries:United StatesLebanonUnited Kingdom
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Frequently asked questions about IW-1701

What is IW-1701 used for?

IW-1701, also known as olinciguat, is an investigational small molecule being studied for use in sickle cell disease. It has been evaluated in clinical trials involving patients with sickle cell disease as well as in healthy volunteers. The drug is not approved and remains in clinical development.

What does IW-1701 target?

IW-1701 targets soluble guanylate cyclase (sGC), an enzyme involved in cellular signaling. As a stimulator of sGC, it is being investigated for its potential effects in conditions like sickle cell disease. This mechanism was the focus of its early clinical trials in healthy subjects.

Who makes IW-1701?

IW-1701 is being developed by Cyclerion Therapeutics, Inc., a biopharmaceutical company. The company's stock is traded under the ticker symbol CYCN. Cyclerion has conducted clinical trials of IW-1701 in the United States and other countries.

What phase is IW-1701 in?

IW-1701 has completed Phase 1 and Phase 2 clinical trials. Two Phase 1 trials in healthy volunteers and one Phase 2 trial in patients with sickle cell disease have been completed. The drug is investigational and has not received FDA approval.

What clinical trials is IW-1701 in?

IW-1701 has been studied in three completed clinical trials. These include NCT02572349 and NCT02792998, both Phase 1 trials in healthy volunteers, and NCT03285178, a Phase 2 trial in patients with sickle cell disease. All trials have been completed.

Is IW-1701 the same as olinciguat?

Yes, IW-1701 is also known as olinciguat. The Phase 2 trial in sickle cell disease refers to the drug as olinciguat, while earlier trials used the name IW-1701. Both names refer to the same investigational small molecule developed by Cyclerion Therapeutics.