Safety and Immunotherapeutic Activity of an Anti-PD-1 Antibody (Cemiplimab) in Participants With HIV-1 on Suppressive cART

NCT03787095 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: ACTG A537038399
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study was to evaluate the safety and immunotherapeutic activity of an anti-PD-1 antibody (cemiplimab) in participants with HIV-1 on suppressive combination antiretroviral therapy (cART).

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Count of Participants With a Grade >=3 Adverse Event (AE) or Grade >=1 Immune-related AE (irAE) Related to Study Treatment

  Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines

  Study Entry through Week 48 or premature discontinuation

• Count of Participants With a Grade >=1 irAE Related to Study Treatment

  Relationship to study treatment was judged by the Clinical Management Committee (CMC), blinded to treatment arm. Immune-related AEs include, but were not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Infusion reactions, adrenal insufficiency, and pneumonitis were graded per the National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 guidelines

  Study Entry through Week 48 or premature discontinuation

Secondary Outcomes (4)

• Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for CD107a and Interferon Gamma (IFNg) From Baseline to Post-baseline

  Baseline through Week 12

• Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg or CD107a Alone From Baseline to Post-baseline

  Baseline through Week 12

• Change in Polyfunctional Response of HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg, CD107a, IL-2, and Tumor Necrosis Factor Alpha (TNFa) From Baseline to Post-baseline

  Baseline through Week 12

• Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg and CD107a After Each Infusion

  Baseline through Week 12

Study Arms (2)

Cohort 1: Cemiplimab

EXPERIMENTAL

Participants received 0.3 mg/kg of cemiplimab, administered at Day 0 and Week 6 for a total of two infusions. Participants continued their current non-study provided ART regimen.

Biological: Cemiplimab

Cohort 1: Placebo

PLACEBO COMPARATOR

Participants received placebo, administered at Day 0 and Week 6 for a total of two infusions. Participants continued their current non-study provided ART regimen.

Biological: Placebo

Interventions

Cemiplimab BIOLOGICAL

Administered as an intravenous (IV) infusion

Also known as: REGN2810

Cohort 1: Cemiplimab

Placebo BIOLOGICAL

Diluent for REGN2810, administered as an IV infusion

Cohort 1: Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1 infection
• On ART for at least 24 months
• Receiving ART with no changes of the components of ART medications within 90 days prior to study entry
• Changes within drug class, in drug formulation or dose are allowed more than 30 days prior to study entry.
• CD4+ T cell count ≥350 cells/mm\^3
• At least two plasma HIV-1 RNA less than the quantification limit of an FDA-approved assay within 18 months
• A single detectable HIV-1 RNA but less than 1000 copies/mL is allowed if followed by HIV-1 RNA below quantifiable limits.
• HIV-1 RNA level less than the quantification limit of an FDA-approved assay within 90 days prior to study entry
• The following laboratory values within 90 days prior to entry:
• Absolute neutrophil count (ANC) ≥1500 cells/mm\^3
• Hemoglobin ≥14.0 g/dL for men and ≥12.0 g/dL for women
• Platelet count ≥150,000/mm\^3
• Creatinine clearance ≥60 mL/min
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal limits
• Normal thyroid, adrenal and diabetes testing

You may not qualify if:

• History of malignancy within the last 5 years.
• HIV-related opportunistic infections within the last 5 years
• Chronic obstructive pulmonary disease (COPD).
• Prior radiation therapy.
• Active or previously treated active TB.
• Active asthma requiring any treatment in the prior 2 years
• Type I or type II diabetes mellitus.
• History of or active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, hypophysitis, or sarcoidosis.
• Immune deficiency other than that caused by HIV infection.
• Currently breastfeeding or pregnant.
• Known allergy/sensitivity or any hypersensitivity to mAb-based biologics, cemiplimab (anti-PD-1) or its formulation.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Receipt of investigational drug or use of investigational medical device within 6 months prior to study entry.
• Use of or intent to use immunomodulators (e.g., interleukins, interferons, cyclosporine, systemic corticosteroids exceeding physiologic doses), HIV vaccine, or systemic cytotoxic chemotherapy within 60 days prior to study entry.
• NOTE: Participants receiving stable physiologic glucocorticoid doses, defined as prednisone ≤10 mg/day or the equivalent, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving topical corticosteroids will not be excluded.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (3)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (2)

• Gay CL, Bosch RJ, McKhann A, Moseley KF, Wimbish CL, Hendrickx SM, Messer M, Furlong M, Campbell DM, Jennings C, Benson C, Overton ET, Macatangay BJC, Kuritzkes DR, Miller E, Tressler R, Eron JJ, Hardy WD; A5370 Team. Suspected Immune-Related Adverse Events With an Anti-PD-1 Inhibitor in Otherwise Healthy People With HIV. J Acquir Immune Defic Syndr. 2021 Aug 15;87(5):e234-e236. doi: 10.1097/QAI.0000000000002716. No abstract available.

  PMID: 33929394 RESULT

• Gay CL, Bosch RJ, McKhann A, Cha R, Morse GD, Wimbish CL, Campbell DM, Moseley KF, Hendrickx S, Messer M, Benson CA, Overton ET, Paccaly A, Jankovic V, Miller E, Tressler R, Li JZ, Kuritzkes DR, Macatangay BJC, Eron JJ, Hardy WD; A5370 Team. Safety and Immune Responses Following Anti-PD-1 Monoclonal Antibody Infusions in Healthy Persons With Human Immunodeficiency Virus on Antiretroviral Therapy. Open Forum Infect Dis. 2024 Jan 11;11(3):ofad694. doi: 10.1093/ofid/ofad694. eCollection 2024 Mar.

  PMID: 38449916 DERIVED

Related Links

• Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
• National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0

MeSH Terms

Conditions

HIV Infections

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

The study was terminated early due to adverse events and was not able to fully evaluate the efficacy outcomes due to the small number of accrued participants.

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Cynthia Gay, MD

  Chapel Hill CRS

  STUDY CHAIR

• W. David Hardy, MD

  Johns Hopkins University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2018
• First Posted: December 26, 2018
• Study Start: August 13, 2019
• Primary Completion: August 18, 2020
• Study Completion: August 18, 2020
• Last Updated: March 2, 2022
• Results First Posted: December 9, 2021

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? * To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at:https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

US (3)