A Study to Evaluate the Efficacy and Safety of Itolizumab in Subjects Hospitalized With COVID-19 (EQUINOX)

• ClinicalTrials.gov Identifier: NCT04605926
• Recruitment Status: Withdrawn
• First Posted: October 28, 2020
• Last Update Posted: January 27, 2021
• Sponsor: Equillium
• Collaborator: Biocon Limited
• Information provided by (Responsible Party): Equillium

Study Description

Brief Summary:

This is a randomized controlled trial to evaluate the efficacy and safety of itolizumab in subjects hospitalized with COVID-19.

Condition or disease	Intervention/treatment	Phase
Coronavirus	Biological: EQ001; Biological: EQ001 Placebo	Phase 3

Detailed Description:

This study will randomize up to 800 subjects in a 1:1 ratio; itolizumab vs. placebo. Subjects will receive either itolizumab or placebo administered intravenously on Day 1 and Day 8 with follow-up to Day 90. Two interim analyses of futility are planned. The first will take place when approximately 20% of the subjects have been evaluated for the primary endpoint, and the second will take place when approximately 50% of the subjects have been evaluated for the primary endpoint.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The study will be blinded to all study staff that has direct access to the subjects and the sponsor.
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Itolizumab in Subjects Hospitalized With COVID-19
• Estimated Study Start Date: November 2020
• Estimated Primary Completion Date: April 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: EQ001; EQ001 administered in a blinded fashion by intravenous infusion on Day 1 and Day 8 for a total of 2 doses.	Biological: EQ001; itolizumab [Bmab600]; Other Names: itolizumab; Bmab600
Placebo Comparator: EQ001 Placebo; Placebo administered in a blinded fashion by intravenous infusion on Day 1 and Day 8 for a total of 2 doses.	Biological: EQ001 Placebo; EQ001 Placebo

Outcome Measures

Primary Outcome Measures :

1. Proportion of subjects who have recovered at Day 28. [ Time Frame: Day 28 ]
   Proportion of subjects who have recovered at Day 28.

Secondary Outcome Measures :

1. Proportion of subjects deceased or requiring mechanical ventilation at Day 28. [ Time Frame: Day 28 ]
   Proportion of subjects deceased or requiring mechanical ventilation at Day 28.
2. Proportion of subjects deceased at Day 28. [ Time Frame: Day 28 ]
   Proportion of subjects deceased at Day 28.

Other Outcome Measures:

1. Incidence of treatment-emergent adverse events (TEAEs). [ Time Frame: Day 90 ]
   Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
2. Time to maximum itolizumab serum concentration, Tmax [ Time Frame: Day 28 ]
   Time to maximum itolizumab serum concentration, Tmax
3. Maximum itolizumab serum drug concentration, Cmax [ Time Frame: Day 28 ]
   Maximum itolizumab serum drug concentration, Cmax
4. Total itolizumab exposure across time, AUC (from zero to last) [ Time Frame: Day 28 ]
   Total itolizumab exposure across time, AUC (from zero to last)
5. Inflammatory biomarkers [ Time Frame: Day 28 ]
   Including but not limited to IL-1, IL-6, IL-17, TNF-α.
6. Pharmacodynamic markers [ Time Frame: Day 28 ]
   sCD6, sALCAM

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Is willing and able to, or has a legally acceptable representative who is willing and able to, provide informed consent to participate and to cooperate with all aspects of the protocol.
2. Is male or female, age ≥18 years
3. Is hospitalized with COVID-19 pneumonia with a diagnosis of SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or equivalent local test within 14 days of randomization.
4. Has PaO2/FiO2 ratio of ≤200 (or equivalent SpO2/FiO2 ratio ~235 within 24 hours before randomization. This ratio may be adjusted based on altitude.

Exclusion Criteria:

1. Has known severe allergic reactions to mAbs.
2. Has active TB or known history of inadequately treated latent or active TB.
3. Has any known active systemic or pulmonary bacterial, fungal, or viral (other than SARS-CoV-2) infection at the time of randomization.
4. Has known active, uncontrolled hepatitis B or hepatitis C or severe liver function impairment from any etiology, as defined by Child-Pugh Class C.
5. Has human immunodeficiency virus (HIV) with known CD4 counts <0.2 × 10^9/L.
6. Has a history of clinically significant cardiac abnormality within 6 months prior to randomization, such as myocardial infarction or stroke, New York Heart Association class III or IV, or clinically significant abnormalities of electrocardiogram (ECG) or cardiac function.
7. Has been on mechanical ventilation for longer than 48 hours during their first continuous episode since admission, is on their second or greater episode of mechanical ventilation at the time of randomization during the concurrent hospitalization, or has received extracorporeal membrane oxygenation (ECMO).
8. Has a declining clinical status with an expected survival <3 days in the opinion of the Investigator.
9. Has received any systemic immunomodulatory or immunosuppressant agents for any condition within 3 months prior to randomization. (Note: a stable, oral, low dose of corticosteroids [prednisone or equivalent ≤10 mg/day] for a chronic condition or any dose of systemic corticosteroids for current COVID-19 treatment are permitted. Local/topical treatments are also permitted.)
10. Has received any biologic treatment for any acute (eg, COVID-19) or chronic conditions (eg, TNFα inhibitors, anti-IL17A, tocilizumab, anti-cytokines, etc.) within 3 months prior to randomization.
11. Is participating in another clinical study of an investigational product and/or received an investigational product within 30 days or within 5 half-lives (whichever is longer) prior to randomization.
12. Is pregnant or breastfeeding, or has a positive pregnancy serum or urine test during Screening.
13. Does not agree to use contraception in the event of sexual activity for 130 days (+90 days for male subjects) after the last dose of study drug if a female of childbearing potential or a male with a partner of childbearing potential. Note: this criterion does not apply to subjects in same-sex relationships.

14. Has inadequate hematologic function during Screening defined as follows:

    • Absolute neutrophil count (ANC) <1.0 × 109/L.
    • ALC <0.5 × 109/L.
15. Requires renal dialysis, either acute or chronic, at the time of randomization.
16. Has a medical, psychiatric, or other condition or circumstance that, in the opinion of the Investigator, could affect the subject's safety, the subject's participation in the study, or the reliability of the study data.

Contacts and Locations

Locations

Colombia

Inv Site CO01

Medellín, Colombia

Sponsors and Collaborators

Equillium

Biocon Limited

Investigators

• Study Director: Maple Fung, MD; Equillium

More Information

Additional Information:

Company website 

• Responsible Party: Equillium
• ClinicalTrials.gov Identifier: NCT04605926
• Other Study ID Numbers: EQ001-20-001
• First Posted: October 28, 2020
• Last Update Posted: January 27, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Equillium:

COVID-19; SARS-CoV-2

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases