A phase 2b, randomized, double-blind study of redasemtide (S-005151) in adult participants with acute ischemic stroke

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Shionogi B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

16 Feb 2024 → ongoing

Decision date (initial)

2023-07-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-501890-38-00

ClinicalTrials.gov

NCT05953480

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare the efficacy of redasemtide with that of placebo

Conditions and MedDRA coding

acute ischemic stroke

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1.Male or female adults ≥ 18 years of age (or complies with country-specific regulatory requirements) at the time of obtaining informed consent
2. 10.Body weight of ≥ 30 to ≤ 150 kg
3. 11.A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: - Is a woman of nonchildbearing potential (WONCBP) as defined in Section 10.4.1 (Appendix 4) OR - Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as described in Section 10.4 (Appendix 4) during the 5-day Treatment Period. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. A WOCBP (defined in Section 10.4.1 [Appendix 4]) must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are provided in Section 8.3.6. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
4. 7. Cohort A: If a participant is not eligible for systemic thrombolysis and/or mechanical recanalization therapy, Screening and Baseline NIHSS score of to 22 (inclusive) is required and must be stable, defined as absence of an increase or decrease of ≥ 4 points within ≥ 1 hour to ≤ 3 hours Screening, and NIHSS score should be 6 to 22 at Baseline.
5. 2.Capable of giving signed informed consent as described in the ICF that includes compliance with the national requirements and the requirements and restrictions listed in the ICF and in this protocol. If the participant cannot provide consent, consent from the participant’s proxy/legally authorized representative (LAR) is allowed according to local regulations. Note: Country-specific rules and local Ethics Committee approval for proxy/LAR will determine whether or not and how a participant unable to comprehend or sign the ICF is allowed to be enrolled in the study.
6. 3.Diagnosis of supratentorial (including anterior and posterior circulation) ischemic stroke as the main infarction site, confirmed by computed tomography (CT) scan or magnetic resonance imaging (MRI) at the time of screening. The CT imaging criteria are hypodensity, perfusion deficit, or vessel occlusion in the anterior or posterior circulation.
7. 4.Able to initiate study intervention within 25 hours of stroke onset (if the onset time is unknown, the last time at which the participant was known to be healthy is regarded as the onset time [“last known to be well”])
8. 5. Cohort A: Determined by the investigator to not be eligible for systemic thrombolysis and/or mechanical recanalization therapy (ie, mechanical thrombectomy, local fibrinolytic therapy as per local standard of care) for the current stroke as detailed in the Participant Hospitalization Sheet. For every randomized participant, the investigator should complete the Participant Hospitalization Sheet (see Section 8) prior to randomization, including the reason for the participant not being eligible for thrombolytic therapy. (Note: Participants who underwent mechanical thrombectomy, but for whom a stent could not be placed to reach the occluded vessel site may be eligible for this study.) Please refer to the most recent tPA package for contraindications.
9. 6 Cohort B: Determined by the investigator to be eligible for systemic thrombolysis and/or mechanical recanalization therapy (ie, mechanical thrombectomy, local fibrinolytic therapy as per local standard of care) for the current stroke as detailed in the Participant Hospitalization Sheet. Initiation of systemic thrombolysis must occur within the country-specific established clinical window from the onset of stroke and mechanical recanalization therapy must occur within 24 hours from the onset of stroke. Note: Thrombolytic agent includes not only recombinant human tPA, but also its engineered derivatives.
10. 9.Medically stable at the time of enrollment except for primary disease and complications associated with it, according to the judgment of the investigator. In addition, hospitalization during the Follow-up Period is not anticipated, and the participant appears likely to be able to complete the study
11. 8.Cohort B: In a participant who is eligible to receive or have received concomitant systemic thrombolysis and/or mechanical recanalization therapy, the NIHSS score must be 6 to 22 at Screening prior to systemic thrombolysis and/or mechanical recanalization therapy and the second /Baseline NIHSS score must be 6 to 22 and should be collected after systemic thrombolysis and/or mechanical recanalization therapy. The investigator should ensure the participant is fully recovered from sedation and/or anesthesia for mechanical recanalization therapy prior to confirmation of NIHSS score.

Exclusion criteria 15

1. Any disease or neurological disorder that, in the opinion of the investigator, would interfere with the conduct of the study
2. A severe decrease in consciousness level (defined as NIHSS item 1a score 3: Not alert, responds only with reflex motor or autonomic effects, or totally unresponsive, flaccid, and areflexic)
3. Disability corresponding to a mRS score of ≥ 2 before the onset of stroke
4. A history of stroke (excluding transient ischemic attack), history of or current intracranial hemorrhage, or head trauma that caused neurological effects within 90 days prior to obtaining informed consent
5. Participants with an ischemic stroke in cerebellum and/or brain stem as the main infarction site
6. Diagnosis of a current transient ischemic attack
7. Unable to undergo either CT or MRI
8. Considered by the investigator to be inappropriate to participate due to a history or complication of serious cardiovascular disease within 1 month of screening (eg, history of acute myocardial infarction, current acute myocardial infarction, uncontrollable heart failure, infective endocarditis requiring treatment, or acute aortic dissection, or requiring or likely to require hospitalization for severe arrhythmia during the study)
9. Blood glucose level < 50 or > 400 mg/dL after glycemic control
10. Systolic blood pressure ≥ 220 mm Hg or diastolic blood pressure ≥ 120 mm Hg after antihypertensive treatment
11. Any malignant tumor except nonmelanoma skin cancer or lesions equivalent to intramucosal cancer or carcinoma in situ curable by endoscopic resection. OR if the participant with a malignant tumor is undergoing or has completed systemic anti-cancer treatment (chemotherapy, immunotherapy) or radiotherapy within 1 month prior to Screening and is not medically stable based on the assessment of the investigator
12. Sensitivity to any of the study interventions, or components thereof, or clinically significant drug or other severe allergy that, in the opinion of the investigator, contraindicates participation in the study
13. Use of prohibited concomitant medications or therapies listed in Section 6.8 for the treatment of current AIS
14. Participants who have previously received redasemtide
15. Participants who have received any investigational product within 90 days of Screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. mRS score at Day 90

Secondary endpoints 17

1. 1.Proportion of participants with mRS score of 0 to 2 at Day 90
2. 2.Proportion of participants with BI score ≥ 95 at Day 90
3. 3.mRS score at Day 30
4. 4.mRS score at Day 180
5. 5.Proportion of participants with mRS score of 0 or 1 at each visit
6. 6.Proportion of participants with mRS score of 0 to 2 at each visit except Day 90
7. 7.Proportion of participants with mRS score of 5 or 6 at each visit
8. 8.Proportion of participants with NIHSS score of 0 or 1 at each visit
9. 9.Proportion of participants with improvement from baseline of at least 8 points in NIHSS score at each visit
10. 10.Proportion of participants with NIHSS score deterioration of at least 4 points from baseline at each visit
11. 11.Change from baseline in NIHSS score at each visit
12. 12.Proportion of participants with BI score ≥ 95 at each visit except Day 90
13. 13.Change from Day 5 in SF-36 at each visit
14. 14.Change from Day 5 in SAQoL-39g at each visit
15. 15.PGI-C at each visit
16. 16.Change from Day 5 in PGI-S at each visit
17. 17.TEAEs, clinical laboratory tests, vital sign measurements (blood pressure, body temperature, respiratory rate, and pulse rate), ECGs and C-SSRS.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Shionogi B.V.

Sponsor organisation

Shionogi B.V.

Address

Herengracht 464

City

Amsterdam

Postcode

1017 CA

Country

Netherlands

Scientific contact point

Organisation

Shionogi B.V.

Contact name

Medical Sciences

Public contact point

Organisation

Shionogi B.V.

Contact name

Medical Sciences

Third parties 11

Locations

9 EU/EEA countries · 71 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 208 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications