A Multicenter, Adaptive, Randomized, Controlled Trial Platform To Evaluate Safety and Efficacy of Strategies and Treatments for Hospitalized Patients with Respiratory Infections

• Register: KCT
• Last refreshed on: 29 April 2024
• Main ID: KCT0008917
• Date of registration: 2023-11-01
• Prospective Registration: Yes
• Primary sponsor: Seoul National University Bundang Hospital
• Public title: A Multicenter, Adaptive, Randomized, Controlled Trial Platform To Evaluate Safety and Efficacy of Strategies and Treatments for Hospitalized Patients with Respiratory Infections
• Scientific title: A Multicenter, Adaptive, Randomized, Controlled Trial Platform To Evaluate Safety and Efficacy of Strategies and Treatments for Hospitalized Patients with Respiratory Infections
• Date of first enrolment: 2024-04-22
• Target sample size: 50
• Recruitment status: Recruiting
• URL: https://cris.nih.go.kr/cris/search/detailSearchEn.do?seq=27321
• Study type: Interventional Study
• Study design: Primary Purpose : Treatment, Intervention Model : Parallel, Blinding/Masking : Double, Blinding Target : Subject, Investigator, Allocation : RCT
• Phase: Phase4

Countries of recruitment

Korea, Republic of

Contacts

• Name: Eu Suk Kim
• Affiliation: Seoul National University Bundang Hospital

• Name: Ji Young Kwak
• Affiliation: Seoul National University Bundang Hospital

Key inclusion & exclusion criteria

Inclusion criteria: 1. Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non-NAT test [list of approved tests in the PIM] collected within 14 days of randomization.
2. Requiring hospitalization for the management of COVID-19.
3. 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.
4. 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.
5. 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.
6. Investigator agrees that the pneumonia is due to COVID-19.
Exclusion criteria: 1. 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.
2. 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).
3. Participant anticipated to not meet all inclusion criteria within 24 hours of randomization in the opinion of the investigator.
4. Allergy to investigational agent.
5. 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.
6. 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.
7. 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.
8. 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).
9. 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.
10.Pre-existing immunomodulation or immunosuppression that meets any of the following:
a. Participant has received abatacept for an indication other than COVID19 within 5 half-lives (65 days) of enrollment (Abatacept elimination halflife 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.
11.Pregnancy or intention to become pregnant within 60 days of randomization.
12.Currently breastfeeding.
13.Co-enrollment in other trials not predetermined to be compatible with this trial.
14.In the investigator’s judgment, the participant has any advanced organ dysfunction that would not make participation appropriate.
15.The treating clinician expects inability to participate in trial p

Age minimum: 18(Year)
Age maximum: No Limit
Gender: Both

Health Condition(s) or Problem(s) studied

Codes for special purposes

Intervention(s)

Drug : Randomization will be 1:1 allocation to active (i.e., abatacept) plus SOC or matched placebo plus SOC. Blinding will be accomplished by use of matching 0.9% saline infusion, with an amber sleeve placed over the infusion bags of both active agent and placebo. All participants and study personnel will be blinded, with the exception of the DSMB, the unblinded statisticians responsible for preparing the closed DSMB reports, and the site pharmacist(s) responsible for preparing the infusion bag.
Abatacept (Brand name - ORENCIA) for Injection is a lyophilized powder for IV 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.

Primary Outcome(s)

The primary safety endpoint for this trial will be a composite of grade 3/4 AEs, protocol-defined adverse clinical events (PDACEs), SAEs, and death through Day 28.

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.‘Days to Recovery Scale’ assessed over 60 days (DRS-60)

Secondary Outcome(s)

Other important safety outcomes are the composite of grade 3/4 AEs, SAEs, PDACEs, or death through Day 5; death and the composite of SAEs, PDACEs, or death through Day 60; and the composite of CRIs and death through Day 60 and Day 120.

time to sustained recovery though Day 60

the pulmonary ordinal outcome on Days 5, 14, and 28

time to progression (as defined elsewhere in this document) through Day 60

all-cause mortality though Day 60

clinically relevant infections (CRIs) through Day 120.

) three-category ordinal outcome, assessed at Day 60, with categories “recovered (alive and at home at Day 60)”, “alive and not recovered”, and dead

Secondary ID(s)

NCT05822583

Source(s) of Monetary Support

National Institutes of Health

Ethics review

Status: Submitted approval
Approval date: 26/09/2023
Contact:

Central Institutional Review Board

[phone]