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NCT03285178: STRONG SCD

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

Completed Phase 2 Results posted Last updated 21 July 2023
What this trial tests

Phase 2 trial testing IW-1701 in Sickle Cell Disease in 88 participants. Completed in 22 July 2020.

Timeline
22 December 2017
Primary endpoint
22 July 2020
22 July 2020

Quick facts

Lead sponsorCyclerion Therapeutics
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment88
Start date22 December 2017
Primary completion22 July 2020
Estimated completion22 July 2020
Sites37 locations across United Kingdom, United States, Lebanon

Drugs / interventions tested

Conditions studied

Sponsor

Cyclerion Therapeutics — full company profile →

Who can join

Adults 16 to 70, any sex, with Sickle Cell Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Primary · 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=mil

Participants with >=1 TEAE
GroupValue95% CI
Double-Blind Treatment: Placebo 16
Double-Blind Treatment: Placebo 26
Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg5
Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg5
Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg8
Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg21
Participants with >=1 Grade 3-5 TEAE
GroupValue95% CI
Double-Blind Treatment: Placebo 12
Double-Blind Treatment: Placebo 22
Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg2
Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg3
Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg4
Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg7
Participants with >=1 Study Drug-Related TEAE
GroupValue95% CI
Double-Blind Treatment: Placebo 13
Double-Blind Treatment: Placebo 20
Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg2
Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg0
Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg4
Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg7
Participants with >=1 SAE
GroupValue95% CI
Double-Blind Treatment: Placebo 12
Double-Blind Treatment: Placebo 21
Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg2
Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg3
Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg4
Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg6
Participants with >=1 TEAE Leading to Study Drug Discontinuation
GroupValue95% CI
Double-Blind Treatment: Placebo 10
Double-Blind Treatment: Placebo 20
Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg0
Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg0
Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg0
Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg2
Participants with >=1 AESI
GroupValue95% CI
Double-Blind Treatment: Placebo 10
Double-Blind Treatment: Placebo 20
Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg0
Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg0
Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg0
Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg1
Double-Blind Treatment: Number of TEAE Events Primary · 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=l

GroupValue95% CI
Placebo 126
Placebo 229
IW-1701 (Olinciguat) 2 mg36
IW-1701 (Olinciguat) 4 mg30
IW-1701 (Olinciguat) 6 mg39
IW-1701 (Olinciguat) 18 mg101
Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity Primary · 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=l

Participants with ≥1 TEAE: Any
GroupValue95% CI
Placebo 16
Placebo 26
IW-1701 (Olinciguat) 2 mg5
IW-1701 (Olinciguat) 4 mg5
IW-1701 (Olinciguat) 6 mg8
IW-1701 (Olinciguat) 18 mg21
Participants with ≥1 TEAE: Grade 1
GroupValue95% CI
Placebo 10
Placebo 24
IW-1701 (Olinciguat) 2 mg0
IW-1701 (Olinciguat) 4 mg2
IW-1701 (Olinciguat) 6 mg2
IW-1701 (Olinciguat) 18 mg6
Participants with ≥1 TEAE: Grade 2
GroupValue95% CI
Placebo 14
Placebo 20
IW-1701 (Olinciguat) 2 mg3
IW-1701 (Olinciguat) 4 mg0
IW-1701 (Olinciguat) 6 mg2
IW-1701 (Olinciguat) 18 mg8
Participants with ≥1 TEAE: Grade 3
GroupValue95% CI
Placebo 12
Placebo 22
IW-1701 (Olinciguat) 2 mg2
IW-1701 (Olinciguat) 4 mg3
IW-1701 (Olinciguat) 6 mg4
IW-1701 (Olinciguat) 18 mg7
Participants with ≥1 TEAE: Grade 4
GroupValue95% CI
Placebo 10
Placebo 20
IW-1701 (Olinciguat) 2 mg0
IW-1701 (Olinciguat) 4 mg0
IW-1701 (Olinciguat) 6 mg0
IW-1701 (Olinciguat) 18 mg0
Participants with ≥1 TEAE: Grade 5
GroupValue95% CI
Placebo 10
Placebo 20
IW-1701 (Olinciguat) 2 mg0
IW-1701 (Olinciguat) 4 mg0
IW-1701 (Olinciguat) 6 mg0
IW-1701 (Olinciguat) 18 mg0
Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs Primary · 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=l

GroupValue95% CI
Placebo 13
Placebo 20
IW-1701 (Olinciguat) 2 mg2
IW-1701 (Olinciguat) 4 mg0
IW-1701 (Olinciguat) 6 mg4
IW-1701 (Olinciguat) 18 mg7

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Single-Blind Run-in Period: Placebo
Serious: 2/88 (2%)
Deaths: 0/88
Double-Blind Treatment Period: Placebo 1
Serious: 2/9 (22%)
Deaths: 0/9
Double-Blind Treatment Period: Placebo 2
Serious: 1/8 (13%)
Deaths: 0/8
Double-Blind Treatment Period: IW-1701 (Olinciguat) 2 mg
Serious: 2/8 (25%)
Deaths: 0/8
Double-Blind Treatment Period: IW-1701 (Olinciguat) 4 mg
Serious: 3/8 (38%)
Deaths: 0/8
Double-Blind Treatment Period: IW-1701 (Olinciguat) 6 mg
Serious: 4/11 (36%)
Deaths: 0/11
Double-Blind Treatment Period: IW-1701 (Olinciguat) 18 mg
Serious: 6/24 (25%)
Deaths: 0/24

Serious adverse events (10 terms)

ReactionSystemSingle-Blind Run-in Period…Double-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…
SICKLE CELL ANAEMIA WITH CRISISBlood and lymphatic system disorders
ACUTE CHEST SYNDROMERespiratory, thoracic and mediastinal disorders
APLASTIC ANAEMIABlood and lymphatic system disorders
IMPAIRED GASTRIC EMPTYINGGastrointestinal disorders
MENORRHAGIAReproductive system and breast disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
NON-CARDIAC CHEST PAINGeneral disorders
PNEUMONIAInfections and infestations
ABDOMINAL PAINGastrointestinal disorders
INTERVERTEBRAL DISC PROTRUSIONMusculoskeletal and connective tissue disorders
Other adverse events (103 terms — click to expand)

ReactionSystemSingle-Blind Run-in Period…Double-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…
HEADACHENervous system disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
BACK PAINMusculoskeletal and connective tissue disorders
SICKLE CELL ANAEMIA WITH CRISISBlood and lymphatic system disorders
VOMITINGGastrointestinal disorders
ABDOMINAL PAIN UPPERGastrointestinal disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
URINARY TRACT INFECTIONInfections and infestations
DIARRHOEAGastrointestinal disorders
ABDOMINAL PAINGastrointestinal disorders
NAUSEAGastrointestinal disorders
FATIGUEGeneral disorders
DECREASED APPETITEMetabolism and nutrition disorders
DYSPEPSIAGastrointestinal disorders
TOOTHACHEGastrointestinal disorders
DIZZINESSNervous system disorders
ANAEMIABlood and lymphatic system disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAINRespiratory, thoracic and mediastinal disorders
NASOPHARYNGITISInfections and infestations
PRURITUSSkin and subcutaneous tissue disorders
DRY SKINSkin and subcutaneous tissue disorders
HYPOTENSIONVascular disorders
INTERVERTEBRAL DISC PROTRUSIONMusculoskeletal and connective tissue disorders
MUSCULAR WEAKNESSMusculoskeletal and connective tissue disorders
BRONCHITISInfections and infestations
GINGIVITISInfections and infestations
SUPRAPUBIC PAINGeneral disorders
NASAL CONGESTIONRespiratory, thoracic and mediastinal disorders
PARANASAL SINUS DISCOMFORTRespiratory, thoracic and mediastinal disorders
RHINORRHOEARespiratory, thoracic and mediastinal disorders
THROAT IRRITATIONRespiratory, thoracic and mediastinal disorders
GASTROOESOPHAGEAL REFLUX DISEASEGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
ABDOMINAL DISCOMFORTGastrointestinal disorders
ABDOMINAL DISTENSIONGastrointestinal disorders
HYPOAESTHESIA ORALGastrointestinal disorders
IMPAIRED GASTRIC EMPTYINGGastrointestinal disorders
MUSCULOSKELETAL PAINMusculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAINMusculoskeletal and connective tissue disorders

Most-reported serious reactions: SICKLE CELL ANAEMIA WITH CRISIS, ACUTE CHEST SYNDROME, APLASTIC ANAEMIA, IMPAIRED GASTRIC EMPTYING, MENORRHAGIA, ARTHRALGIA, NON-CARDIAC CHEST PAIN, PNEUMONIA.

Data from ClinicalTrials.gov NCT03285178 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Inflammation in sickle cell disease.
    Conran N, Belcher JD. · · 2018 · cited 204× · PMID 29614637 · DOI 10.3233/ch-189012
  2. cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.
    Friebe A, Sandner P, Schmidtko A. · · 2020 · cited 102× · PMID 31853617 · DOI 10.1007/s00210-019-01779-z
  3. Drug Therapies for the Management of Sickle Cell Disease.
    Rai P, Ataga KI. · · 2020 · cited 32× · PMID 32765834 · DOI 10.12688/f1000research.22433.1
  4. Current and novel therapies for the prevention of vaso-occlusive crisis in sickle cell disease.
    Osunkwo I, Manwani D, Kanter J. · · 2020 · cited 30× · PMID 33062233 · DOI 10.1177/2040620720955000
  5. Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing.
    Anurogo D, Yuli Prasetyo Budi N, Thi Ngo MH, Huang YH, et al · · 2021 · cited 26× · PMID 34200975 · DOI 10.3390/ijms22126275
  6. Sickle cell disease: progress towards combination drug therapy.
    Pace BS, Starlard-Davenport A, Kutlar A. · · 2021 · cited 24× · PMID 33471938 · DOI 10.1111/bjh.17312
  7. New insights into the pathophysiology and development of novel therapies for sickle cell disease.
    Moerdler S, Manwani D. · · 2018 · cited 24× · PMID 30504350 · DOI 10.1182/asheducation-2018.1.493
  8. cGMP modulation therapeutics for sickle cell disease.
    Conran N, Torres L. · · 2019 · cited 18× · PMID 30691292 · DOI 10.1177/1535370219827276

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03285178.

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