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) - Immune Modulation Strategy Trial

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

28 Nov 2023 → 11 Aug 2025

Decision date (initial)

2025-05-09

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

2023-504487-41-00

ClinicalTrials.gov

NCT05822583

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

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 whether early administration of a second IM (in addition to SOC baseline IM) in hospitalized patients with COVID-19 improves clinical recovery through Day 60 compared with early administration of placebo.

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

European Medicines Agency, Food And Drug Administration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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. Requiring hospitalisantion for the management of COVID-19
6. Has evidence of COVID-19 pneumonia (PNA) defined as either: a. Receiving supplemental low flow oxygen, >0 L/min and ≤2 L/min, with evidence of airspace disease on chest imaging (X-ray, computer tomography or ultrasound). OR b. Receiving supplemental low flow oxygen, >2 L/min and <10 L/min
7. Currently receiving or planned to receive (ordered) one IM drug (for example, a corticosteroid or baricitinib, but NOT abatacept) as part of treatment of COVID-19 prior to randomization.
8. Has started supplemental oxygen for the treatment of COVID-19 within the past 5 calendar days. Patients on home oxygen are eligible if current oxygen flow rate is increased from pre-COVID-19 level and all other study criteria are met.
9. Investigator agrees that the pneumonia is due to COVID-19.

Exclusion criteria 21

1. The patient is expected to be discharged from the hospital within the next 24 hours.
2. Known estimated glomerular filtration rate (eGRF) <30 mL/min/1.73m**2
3. Continuous renal replacement therapy or chronic dialysis
4. Current pregnancy
5. Current breastfeeding and unwillingness to defer breastfeeding for 30 days after the last dose of investigational agent.
6. 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.
7. Oxygen requirement of 10 L/min or more of low flow oxygen (or equivalent if using Venturi mask, etc.), or requiring high-flow oxygen (HFNO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV) or ECMO
8. Received more than one baseline IM for treatment of the current COVID-19 infection at the time of trial enrollment (examples: corticosteroid, baricitinib, tocilizumab, anakinra, abatacept, or infliximab).
9. Participant anticipated to not meet all inclusion criteria within 24 hours of randomization in the opinion of the investigator.
10. Allergy to investigational agent.
11. Neutropenia: absolute neutrophil count <1000 cells/μL (<1.0 x 103/μL or <1.0 x 109/L) on most recent lab within 2 calendar days of randomization
12. Lymphopenia: absolute lymphocyte count <200 cells/μL (<0.20 x 103/μL or <0.20 x 109/L) on most recent lab within 2 calendar days of randomization
13. Known or suspected active or recent serious infection (bacterial, fungal, viral, or parasitic infection, excepting SARS-CoV-2) that in the opinion of the investigator could constitute a risk when taking investigational agent. Note: Broad spectrum empiric antibiotic usage does not exclude participation
14. Known or suspected history of untreated tuberculosis (TB). TB diagnosis may be suspected based on medical history and concomitant therapies that would suggest TB infection. Participants are also excluded if they have known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
15. Received any live vaccine (or live attenuated) within 3 months before screening or intend to receive a live vaccine (or live attenuated) during the trial. Use of prior non-live (inactivated) vaccinations is allowed for all participants, including any vaccine for COVID-19
16. Pre-existing immunomodulation or immunosuppression that meets any of the following: a. Participant has received abatacept for an indication other than COVID-19 within 5 half-lives (65 days) of enrollment (Abatacept elimination half-life is 13.1 days.) b. Participant is receiving immune modulatory therapy for autoimmune, transplant management or another indication AND has one or more of the following: i. evidence of active infection (other than COVID-19) or ii. has required reduction in their immune modulatory therapy in the preceding 6 months due to infectious complication (routine reduction as SOC is not an exclusion) or iii. has required intensification in immune modulatory therapy within the preceding 6 months due to organ rejection/worsening underlying disease status (e.g., intensification with an additional agent on top of usual immunosuppressive regimen). c. Participant has recently received or is anticipated to require immune modulatory agents for their underlying disease including chemotherapeutic treatments likely to induce neutropenia or lymphopenia. d. Participant has untreated advanced HIV (known CD4 <200 cells/mm3 in the past 6 months) AND is not established on antiretroviral therapy.
17. Pregnancy or intention to become pregnant within 60 days of randomization.
18. Currently breastfeeding
19. Co-enrollment in other trials not predetermined to be compatible with this trial.
20. In the investigator’s judgment, the participant has any advanced organ dysfunction that would not make participation appropriate
21. The treating clinician expects inability to participate in trial procedures or participation would not be in the best interests of the patient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome for this trial 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

9 EU/EEA countries · 41 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 14 files

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

Application history

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