Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial

COVID-19 Clinical Trial

Official title:

Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05822583
• Other study ID #: STRIVE
• Status: Recruiting
• Phase: Phase 4
• Start date: July 6, 2023
• Est. completion date: July 1, 2025

Study information

• Verified date: April 2024
• Source: University of Minnesota
• Contact: Cavan Reilly, PhD
• Phone: 612-624-9644
• Email: webe0376[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

COVID-19 can trigger a dysregulated immune response, and previous studies have shown that immune modulation can improve outcomes in hospitalized patients. This trial is designed to determine whether intensification of immune modulation early in the course of the disease (while patients are on low flow oxygen) with abatacept (active arm) combined with standard of care (SOC) improves recovery as compared with placebo + SOC (placebo arm). For both groups, intensification of immunomodulation will be provided as part of SOC in case of signs of disease progression (patient requires high flow nasal oxygen (HFNO) or more support) and/or if the patient has rapidly increasing oxygen requirement.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non-NAT test [list of approved tests in the PIM] within 14 days of randomization.
• Requiring hospitalization for the management of COVID-19
• Has evidence of COVID-19 pneumonia (PNA) defined as either receiving supplementary oxygen =2L of low flow oxygen with evidence of airspace disease on chest imaging (X ray, computer tomography or ultrasound) OR receiving supplementary oxygen >2L and <10 L of low flow oxygen.
• Currently receiving or planned to receive (ordered) one IM drug (for example, a corticosteroid or baricitinib) as part of treatment of COVID-19 prior to randomization.
• 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 baseline and other above criteria are met.
• Investigator agrees that the pneumonia is due to COVID-19.

Exclusion Criteria:

• Oxygen requirement of =10L or more of low flow oxygen (or equivalent if using Venturi mask, etc), or requiring either HFNO, NIV, IMV, or ECMO.
• Participant has received more than one baseline IM for treatment of the current COVID-19 infection at time of trial enrollment. (Examples: corticosteroid, baricitinib, tocilizumab, anakinra, abatacept, or infliximab.)
• Participant anticipated to not meet all inclusion criteria within 24 hours of randomization in the opinion of the investigator.
• Allergy to investigational agent.
• Neutropenia (absolute neutrophil count <1000 cells/µL) (<1.0 x 10 3 /µL or <1.0 G/L) on most recent lab within 2 calendar days of randomization.
• Lymphopenia (absolute lymphocyte count <200 cells/µL) (<0.20 x 10 3 /µL or <0.20 G/L) on most recent lab within 2 calendar days of randomization.
• 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.
• 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).
• Have 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.
• Pre-existing immunomodulation or immunosuppression that meets any of the following:

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.) Participant is receiving immune modulatory therapy for autoimmune, transplant management or another indication AND has one or more of the following: evidence of active infection (other than COVID-19) or 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 has required intensification in immunotherapy 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)

• Participant has recently received or is anticipated to require immune modulatory agents for their underlying disease including chemotherapeutic treatments likely to induce neutropenia (<1.0 x 10 9 cells/µL) or lymphopenia (<1.0 x 10 9 cells/µL)
• Participant has untreated advanced HIV (known CD4 <200 in the past 6 months) AND is not established on antiretroviral therapy
• Pregnancy
• Breastfeeding
• Co-enrollment in other trials not predetermined to be compatible with this trial.
• In the investigator's judgment, the patient has any advanced organ dysfunction that would not make participation appropriate.
• The treating clinician expects inability to participate in trial procedures or participation would not be in the best interests of the patient.

Related Conditions & MeSH terms

• COVID-19
• Emergencies
• Respiratory Tract Infections

Intervention

Drug:
• abatacept infusion
The dose of abatacept will be 10 mg/kg given as a single infusion on Day 0, with a maximum dose of 1,750 mg, so any participant with weight of >175 kg will receive a dose of 1750 mg. + baseline IM (immune modulator)
• Placebo group
Placebo group (IV infusion of normal saline) + baseline IM

Locations

Country	Name	City	State
Australia	Monash Health (612-009)	Clayton	Victoria
Denmark	Aalborg Hospital (Site 625-005)	Aalborg
Denmark	Aarhus Universitetshospital, Skejby (Site 625-002)	Aarhus
Denmark	Bispebjerg Hospital (Site 625-013)	Copenhagen
Denmark	Rigshospitalet, CHIP (Site 625-006)	Copenhagen
Denmark	Herlev/Gentofte Hospital (Site 625-012	Hellerup
Denmark	Nordsjællands Hospital, Hillerød (Site 625-009)	Hillerød
Denmark	Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001)	Hvidovre
Denmark	Odense University Hospital (625-004)	Odense	C
Georgia	AIDS and Clinical Immunology Research Center (627-201)	Tbilisi
Germany	Klinik I für Innere Medizin der Universität zu Köln (622-008)	Cologne
Korea, Republic of	Seoul National University Bundang Hospital (612-904)	Seongnam
Korea, Republic of	Chung-Ang University Hospital (612-902)	Seoul
Korea, Republic of	National Medical Center (612-905)	Seoul
Korea, Republic of	Seoul St. Mary's Hospital (Site 612-903)	Seoul
Spain	Hospital Universitari Germans Trias i Pujol (626-003)	Badalona	Barcelona
Ukraine	Central City Clinical Hospital of Ivano-Frankivsk City Council (627-302)	Ivano-Frankivs'k
United States	Hendrick Medical Center (Site 080-014)	Abilene	Texas
United States	University of New Mexico Hospital (Site 213-008)	Albuquerque	New Mexico
United States	VA Ann Arbor Healthcare System (Site 074-028)	Ann Arbor	Michigan
United States	Emory Grady (Site 301-032)	Atlanta	Georgia
United States	Rocky Mountain Regional VA Medical Center (Site 074-010)	Aurora	Colorado
United States	University of Colorado Hospital (Site 204-001)	Aurora	Colorado
United States	University of Alabama Birmingham University Hospital (Site 213-002)	Birmingham	Alabama
United States	NYU Brooklyn (301-033)	Brooklyn	New York
United States	Lahey Hospital and Medical Center (Site 213-001)	Burlington	Massachusetts
United States	Cooper University Hospital (019-001)	Camden	New Jersey
United States	Medical University of South Carolina (Site 210-002)	Charleston	South Carolina
United States	Ralph H. Johnson VA Medical Center (074-015)	Charleston	South Carolina
United States	University of Illinois at Chicago (008-012)	Chicago	Illinois
United States	Cleveland Clinic Foundation (Site 207-001)	Cleveland	Ohio
United States	Baylor, Scott and White Health (301-003)	Dallas	Texas
United States	Parkland Health and Hospital Systems (084-002)	Dallas	Texas
United States	UT Southwestern Medical Center (084-001)	Dallas	Texas
United States	UC Davis Health (Site 203-004)	Davis	California
United States	Hope Clinic, Emory University (Site 301-031)	Decatur	Georgia
United States	Public Health Institute at Denver Health (Site 017-004)	Denver	Colorado
United States	Henry Ford Health System (014-001)	Detroit	Michigan
United States	Sinai-Grace Hospital (Site 205-005)	Detroit	Michigan
United States	Duke University Hospital (Site 301-006)	Durham	North Carolina
United States	Lutheran Medical Group (301-010)	Fort Wayne	Indiana
United States	UCSF Fresno (Site 203-005)	Fresno	California
United States	Penn State Health Milton S. Hershey Medical Center (Site 209-002)	Hershey	Pennsylvania
United States	Houston Methodist Research Institute (Site 301-028)	Houston	Texas
United States	University of Texas Health Science Center (Site 203-006)	Houston	Texas
United States	University of Mississippi Medical Center (Site 202-005)	Jackson	Mississippi
United States	University of Kansas Medical Center (Site 080-044)	Kansas City	Kansas
United States	Dartmouth-Hitchcock Medical Center (301-024)	Lebanon	New Hampshire
United States	VA Loma Linda Healthcare System (074-017)	Loma Linda	California
United States	VA Long Beach Healthcare System (074-026)	Long Beach	California
United States	Ronald Reagan UCLA Medical Center (Site 203-002)	Los Angeles	California
United States	William S. Middleton Memorial Veterans Hospital (074-030)	Madison	Wisconsin
United States	Froedtert Memorial Lutheran Hospital (052-001)	Milwaukee	Wisconsin
United States	NYU Long Island (301-034)	Mineola	New York
United States	M Health Fairview University of Minnesota Medical Center (112-001)	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University Medicine (Site 301-023)	Morgantown	West Virginia
United States	Intermountain Medical Center (Site 211-001)	Murray	Utah
United States	Vanderbilt University Medical Center (Site 212-001)	Nashville	Tennessee
United States	Mount Sinai Medical Center (Site 301-012)	New York	New York
United States	New York University Langone Health (301-013)	New York	New York
United States	Weill Cornell Clinical Research Unit (065-001)	New York	New York
United States	University of Nebraska Medical Center (Site 080-045)	Omaha	Nebraska
United States	Rhode Island Hospital (Site 080-036)	Providence	Rhode Island
United States	The Miriam Hospital (Site 080-039)	Providence	Rhode Island
United States	Washington University School of Medicine (Site 003-001)	Saint Louis	Missouri
United States	Salem VA Medical Center (Site 074-014)	Salem	Virginia
United States	University of Utah Hospital (211-002)	Salt Lake City	Utah
United States	VA San Diego Healthcare System (074-016)	San Diego	California
United States	San Francisco VAMC (Site 074-002)	San Francisco	California
United States	UCSF Medical Center (Site 203-001)	San Francisco	California
United States	UCSF Medical Center at Mount Zion (203-007)	San Francisco	California
United States	Zuckerberg San Francisco General Hospital and Trauma Center (213-007)	San Francisco	California
United States	Providence (Sacred Heart) (213-004)	Spokane	Washington
United States	Baystate Medical Center (Site 201-001)	Springfield	Massachusetts
United States	Stanford University Hospital & Clinics (Site 203-003)	Stanford	California
United States	Banner University Medical Center Tucson (Site 206-004)	Tucson	Arizona
United States	Southern Arizona VA Healthcare System (Site 074-009)	Tucson	Arizona
United States	MedStar Health Research Institute (Site 009-021)	Washington	District of Columbia
United States	Washington DC VA Medical Center (Site 009-004)	Washington	District of Columbia
United States	Wake Forest Baptist Health (Site 210-001)	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Countries where clinical trial is conducted

United States,  Australia,  Denmark,  Georgia,  Germany,  Korea, Republic of,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days to Recovery Scale	DRS-60 is a version of the STRIVE clinical recovery scale (CRS) which combines time to recovery with non-recovered clinical state and death to an ordinal outcome.0 indicates best results, 60 represents recovered on Day 60, with not recovered by Day 60 coded as 61 and death (worst outcome) as 62.	60 days post-intervention
Secondary	time to sustained recovery though Day 60	Time to sustained recovery is defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to the end of follow-up	baseline to day 60
Secondary	all-cause mortality though Day 60	substantial attempts will be made to determine vital status through the end of follow-up by a combined approach of follow-up visits with the participant or proxy, chart review, and review of other available information sources.	baseline to day 60
Secondary	time to progression	will be defined by the study day on which a participant experiences a definite progression.; Definite progression is defined as a participant requiring HFNO, NIV, IMV, or ECMO therapy, OR, if HFNO is unavailable, a participant requiring =15 L/min conventional oxygen.; Probable progression is defined as a participant not meeting criteria for definite progression but requiring =10 L/min conventional oxygen, OR, a participant with an oxygen requirement that has increased by =4 L/min in the preceding 24 hours.	baseline to day 60
Secondary	Three-category ordinal outcome	assessed at Day 60, with categories "recovered (alive and at home at Day 60)", "alive and not recovered", and dead	Day 60
Secondary	the pulmonary ordinal outcome	categories defined as: Can independently undertake usual activities with minimal or no symptoms; Symptomatic and currently unable to independently undertake usual activities but no need of supplemental oxygen (or not above premorbid requirements); Supplemental oxygen <4 liters/min (or <4 liters/min above premorbid requirements); Supplemental oxygen =4 liters/min (or =4 liters/min above premorbid requirements, but not high-flow oxygen); Non-invasive ventilation or high-flow oxygen; Invasive ventilation, extracorporeal membrane oxygenation (ECMO), mechanical circulatory support, or new receipt of renal replacement therapy; Death	Day 5, 14, and 28