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

• Status: Not yet recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Minnesota
• Treatments: Abatacept

Criteria

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.