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)

Cyclerion Therapeutics

Status and phase: Completed; Phase 2

Conditions: Sickle Cell Disease

Treatments: Drug: Placebo; Drug: IW-1701

Study type: Interventional

Funder types: Industry

Identifiers

NCT03285178

C1701-202

Details and patient eligibility

About

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.

Enrollment: 88 patients

Sex: All

Ages: 16 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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88 participants in 5 patient groups, including a placebo group

IW-1701 (Olinciguat) 2 mg

Experimental group

Description:

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.

Treatment:

Drug: IW-1701

IW-1701 (Olinciguat) 4 mg

Experimental group

Description:

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.

Treatment:

Drug: IW-1701

IW-1701 (Olinciguat) 6 mg

Experimental group

Description:

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.

Treatment:

Drug: IW-1701

IW-1701 (Olinciguat) 18 mg

Experimental group

Description:

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.

Treatment:

Drug: IW-1701

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo