A Multicenter, Adaptive, Randomized, Controlled Trial Platform to Evaluate Safety and Efficacy of Strategies and Treatments for Hospitalized Patients with Respiratory Infections: Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE) - Shionogi Protease Inhibitor (S-217622)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Minnesota

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

31 Jul 2023 → 1 Oct 2025

Decision date (initial)

2023-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Div of Clinical Research/Natl Inst of Allergy & Infectious Diseases/NIH (US)

External identifiers

EU CT number

2022-501020-19-01

ClinicalTrials.gov

NCT05605093

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective of the STRIVE platform is to facilitate the efficient and rigorous execution of randomised clinical trials investigating the safety and efficacy of therapeutic interventions or strategies for acute respiratory infections among hospitalised adults. Each trial within STRIVE will have its own objectives outlined in its trial specific appendix.
The primary objective for each trial will be compared efficacy of the intervention or strategy under investigation with control for the chosen primary outcome among participants randomised in that trial.

The primary objective of this trial is to determine if a 5-day treatment course with S-217622, versus placebo, improves clinical outcomes for patients hospitalized for the management of COVID-19, when given in combination with standard care.

Secondary objectives 6

1. Secondary objectives for each STRIVE trial will include the evaluation of secondary outcomes, evaluation for heterogeneity of treatment effect, and the enhancement of a pathophysiologic understanding of severe respiratory infections through the collection and analysis of biospecimens.
2. Mortality (proportion of participants who died by Day 60
3. 3-category ordinal outcome assessed at day 60, alive and not recovered, and dead
4. Time to recovery
5. Proportion of participants who died or required new invasive mechanical ventilation
6. Safety as measured by composite of death, Serious Adverse Events, protocol-defined anticipated clinical events and grade 3 or 4 adverse events

Conditions and MedDRA coding

COVID-19

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥18 years
2. Informed consent for trial participation
3. Hospital admission (or boarding in an emergency department or other area awaiting hospital admission) with signs and/or symptoms of a respiratory infection
4. Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non-NAT test collected within the prior 14 days
5. Onset of symptoms attributable to SARS-CoV2 infection occurred within 14 days before randomization
6. Hospitalized for the management of COVID-19, with signs and/or symptoms suggestive of lower respiratory tract infection

Exclusion criteria 16

1. The patient is expected to be discharged from the hospital within the next 24 hours.
2. Medical condition other than the acute respiratory infection (and its manifestations) that is likely to result in death within 7 days of randomization
3. Moribund condition, defined as prior cardiac arrest during this hospitalization and life expectancy less than 48 hours of randomization
4. Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life
5. Expected inability or unwillingness to participate in study procedures.
6. In the opinion of the investigator, participation in a trial is not in the best interest of the patient.
7. Allergy to investigational agent or vehicle
8. Use of a concomitant medication that is contraindicated due to a drug-drug interaction with S-217622
9. Moderate to severe hepatic impairment (i.e., Child-Pugh class B or C) or acute liver failure
10. Known estimated glomerular filtration rate (eGRF) <30 mL/min/1.73m**2
11. Continuous renal replacement therapy or chronic dialysis
12. Current pregnancy
13. Current breastfeeding and unwillingness to defer breastfeeding for 30 days after the last dose of investigational agent.
14. Women of child-bearing potential who are unwilling to abstain from sexual intercourse with men or practice appropriate contraception through 30 days from the last dose of the investigational agent.
15. Men who are unwilling to abstain from sexual intercourse with women of child-bearing potential or to use barrier contraception through 30 days from the last dose of the investigational agent.
16. Inability to take investigational agent in tablet form by mouth. NOTE: the exclusion criterion for patients unable to take the oral formulation of S-217622 (or placebo) may be removed if stability testing supports enteral administration of crushed tablets. If available data supports enteral administration of S-217622 (or placebo), then this exclusion would be removed and patients unable to take oral tablets would be eligible, e.g., those on invasive mechanical ventilation or ECMO

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome for this trial with S-217622 is called the "Days to Recovery Scale" assessed over 60 days (DRS-60). DRS-60 is a version of the STRIVE clinical recovery scale (CRS) that is described in the master protocol, which combines time to recovery with non-recovered clinical state and death into an ordinal outcome. For this trial, the DRS-60 version of the CRS includes daily bins for time to recovery with additional categories for alive, not-recovered and death.

Secondary endpoints 5

1. Mortality (proportion of participants who died by Day 60)
2. 3-category ordinal outcome (recovered, alive but not recovered, dead)
3. Time to recovery
4. Death or new requirement for invasive mechanical ventilation
5. Safety as measured by composite of death, Serious Adverse Events, protocol-defined anticipated clinical events, grade 3 Adverse Events, grade 4 Adverse Events

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Minnesota

Sponsor organisation

University Of Minnesota

Address

2221 University Avenue Southeast Suite 200

City

Minneapolis

Postcode

55414-3075

Country

United States

Scientific contact point

Organisation

University Of Minnesota

Contact name

David Vock

Public contact point

Organisation

University Of Minnesota

Contact name

Eileen Denning

Locations

6 EU/EEA countries · 19 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 51 files

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

Application history

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