Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03787095
Recruitment Status : Recruiting
First Posted : December 25, 2018
Last Update Posted : July 16, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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

Condition or disease Intervention/treatment Phase
HIV Infections Biological: Cemiplimab Biological: Placebo Phase 1 Phase 2

Detailed Description:

This study will evaluate the safety and immunotherapeutic activity of an anti-PD-1 antibody (cemiplimab) in HIV-1-infected participants on combination antiretroviral therapy (cART) who have HIV-1 RNA below the limit of quantification and CD4+ T cell counts greater than or equal to 350/mm^3.

Participants will be enrolled into three sequential dose-rising cohorts. Participants in each cohort will receive infusions of either cemiplimab or placebo at study entry (Day 0) and Week 6, for a total of two infusions. All participants will also continue their non-study provided ART regimen. Enrollment in the cohorts will be sequential, with the second and third cohorts receiving the first infusion after all participants in the previous cohort have reached week 12 and an evaluation of safety outcomes is completed.

Participants will attend study visits on Day 0 and Weeks 1, 2, 4, 6, 7, 8, 10, 12, 16, 20, 24, 28, 36, and 48. These visits may include a medical history, physical examination, urine and blood collection, and adherence assessments. Participants will be followed for 48 weeks.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Safety and Immunotherapeutic Activity of an Anti-PD-1 Antibody (Cemiplimab) in HIV-1-infected Participants on Suppressive cART: A Phase I/II, Double-blind, Placebo-controlled, Ascending Multiple Dose Study
Actual Study Start Date : April 8, 2019
Estimated Primary Completion Date : September 2, 2021
Estimated Study Completion Date : December 8, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Cohort 1: Cemiplimab

Participants will receive 0.3 mg/kg of cemiplimab, administered at Day 0 and Week 6 for a total of two infusions.

Participants will also continue their current non-study provided ART regimen.

Biological: Cemiplimab
Administered as an intravenous (IV) infusion
Other Name: REGN2810

Placebo Comparator: Cohort 1: Placebo

Participants will receive placebo, administered at Day 0 and Week 6 for a total of two infusions.

Participants will also continue their current non-study provided ART regimen.

Biological: Placebo
Sodium chloride for injection, administered as an IV infusion

Experimental: Cohort 2: Cemiplimab

Participants will receive 1 mg/kg of cemiplimab, administered at Day 0 and Week 6 for a total of two infusions.

Participants will also continue their current non-study provided ART regimen.

Biological: Cemiplimab
Administered as an intravenous (IV) infusion
Other Name: REGN2810

Placebo Comparator: Cohort 2: Placebo

Participants will receive placebo, administered at Day 0 and Week 6 for a total of two infusions.

Participants will also continue their current non-study provided ART regimen.

Biological: Placebo
Sodium chloride for injection, administered as an IV infusion

Experimental: Cohort 3: Cemiplimab

Participants will receive 3 mg/kg of cemiplimab, administered at Day 0 and Week 6 for a total of two infusions.

Participants will also continue their current non-study provided ART regimen.

Biological: Cemiplimab
Administered as an intravenous (IV) infusion
Other Name: REGN2810

Placebo Comparator: Cohort 3: Placebo

Participants will receive placebo, administered at Day 0 and Week 6 for a total of two infusions.

Participants will also continue their current non-study provided ART regimen.

Biological: Placebo
Sodium chloride for injection, administered as an IV infusion




Primary Outcome Measures :
  1. Occurrence of a Grade 3 or higher adverse event (AE) related to study treatment (as judged by the core team, blinded to treatment arm) [ Time Frame: Study Entry through Week 48 ]
    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

  2. Occurrence of Grade 1 or higher immune-related adverse event (irAE) (such as, but not limited to, pneumonitis, colitis, adrenal insufficiency, or hypothyroidism), related to study treatment (as judged by the core team, blinded to treatment arm) [ Time Frame: Study Entry through Week 48 ]
    Graded according to the DAIDS AE Grading Table, corrected Version 2.1, July 2017


Secondary Outcome Measures :
  1. Frequency of HIV-1 gag-specific CD8+ T cells [ Time Frame: Study Entry through Week 12 ]
    Assessed by intracellular staining for CD107a and interferon gamma

  2. Frequency of HIV-1 gag-specific CD8+ T cells [ Time Frame: Baseline, after first dose (average of Weeks 2-6), after the second dose (average of Weeks 8-12) ]
    Assessed by intracellular staining for CD107a and interferon gamma

  3. Frequency of HIV-1 gag-specific CD8+ T cells [ Time Frame: Baseline, Study Entry through Week 12 ]
    Assessed by intracellular staining for interferon gamma or CD107a alone

  4. Change in polyfunctional response of HIV-1 gag-specific CD8+ T cells [ Time Frame: Baseline, Study Entry through Week 12 ]
    Assessed by intracellular staining for interferon gamma, CD107a, IL-2, and tumor necrosis factor alpha



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 greater than or equal to 350 cells/mm^3
  • At least two plasma HIV-1 RNA below quantifiable limit 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 within 90 days prior to study entry
  • The following laboratory values within 90 days prior to entry:

    • Absolute neutrophil count (ANC) greater than or equal to 1500 cells/mm^3
    • Hemoglobin greater than or equal to 14.0 g/dL for men and greater than or equal to 12.0 g/dL for women
    • Platelet count greater than or equal to 150,000/mm^3
    • Creatinine clearance greater than or equal to 60 mL/min
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal limits
    • Normal thyroid, adrenal and diabetes testing
  • Negative tuberculosis (TB) test result, OR documentation of completed TB prophylaxis treatment
  • HCV antibody negative result or, if HCV antibody positive, undetectable HCV RNA result
  • Negative HBsAg result
  • 18 - 64 years of age
  • Ability and willingness to provide informed consent.
  • Ability and willingness to continue cART throughout the study.
  • Female participants must have a negative pregnancy test. Agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, egg donation) during the study.
  • When participating in sexual activity that could lead to pregnancy, agree to use at least two reliable forms of contraception simultaneously during the study through week 48.
  • Participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy or men who have documented azoospermia or undergone vasectomy) are eligible without requiring the use of contraceptives.
  • Weight greater than or equal to 50 kg (110 pounds)

Exclusion Criteria:

  • History of malignancy within the last 5 years.

    • Prior non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) is not exclusionary with documentation of complete resection at least 3 months prior to enrollment.
  • 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.
  • Received investigational drug or 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 less than or equal to 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.
  • Any vaccination within 30 days
  • HCV treatment within 6 months
  • Prior immunoglobulin (IgG) therapy.
  • Current use or intent to use biotin greater than or equal to 5 mg/day, including within dietary supplements.
  • A history of chronic congestive heart failure or other significant cardiac conditions.
  • Any active clinically significant medical condition that, in the opinion of the site investigator, would place the participant at increased risk.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03787095


Locations
Layout table for location information
United States, Alabama
Alabama CRS Recruiting
Birmingham, Alabama, United States, 35294
Contact: Pamela Cunningham, R.N., B.S.N., M.P.H.    205-975-2841    pamelacunningham@uabmc.edu   
United States, California
UCLA CARE Center CRS Recruiting
Los Angeles, California, United States, 90035
Contact: Aleen Khodabakhshian    310-557-9027    akhodabakhshian@mednet.ucla.edu   
UCSD Antiviral Research Center CRS Recruiting
San Diego, California, United States, 92103
Contact: Steven Hendrickx, R.N.    619-543-6968    smhendrickx@ucsd.edu   
Ucsf Hiv/Aids Crs Recruiting
San Francisco, California, United States, 94110
Contact: Jay Dwyer    415-476-4082 ext 353    Jay.Dwyer@ucsf.edu   
United States, Colorado
University of Colorado Hospital CRS Recruiting
Aurora, Colorado, United States, 80045
Contact: Suzanne Fiorillo, M.S.P.H.    303-724-5931    suzanne.fiorillo@ucdenver.edu   
United States, Georgia
The Ponce de Leon Center CRS Recruiting
Atlanta, Georgia, United States, 30308-2012
Contact: Ericka Patrick, M.S.N.    404-616-6313    erpatri@emory.edu   
United States, Missouri
Washington University Therapeutics (WT) CRS Recruiting
Saint Louis, Missouri, United States, 63110-1010
Contact: Michael K. Klebert    314-747-1098    mklebert@dom.wustl.edu   
United States, New York
Columbia P&S CRS Recruiting
New York, New York, United States, 10032-3732
Contact: Steven Palmer, P.A. -C    212-342-2958    sp500@cumc.columbia.edu   
University of Rochester Adult HIV Therapeutic Strategies Network CRS Recruiting
Rochester, New York, United States, 14642
Contact: Christine Hurley    585-210-4136    Christine_Hurley@urmc.rochester.edu   
United States, North Carolina
Chapel Hill CRS Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Becky Straub, B.S.N., M.P.H., R.N.    919-843-9975    bstraub@med.unc.edu   
United States, Ohio
Cincinnati Clinical Research Site Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Sharon Kohrs, R.N., B.S.N.    513-584-6383    kohrssd@ucmail.uc.edu   
United States, Tennessee
Vanderbilt Therapeutics (VT) CRS Recruiting
Nashville, Tennessee, United States, 37204
Contact: Beverly O. Woodward, M.S.N., R.N.    615-936-8516    beverly.o.woodward@vanderbilt.edu   
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS Recruiting
San Juan, Puerto Rico, 00935
Contact: Sylvia I. Davila Nieves, M.Sc.    787-767-9192    sylvia.davila1@upr.edu   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Study Chair: Cynthia Gay, MD, MD Chapel Hill CRS
Study Chair: W. David Hardy, MD Johns Hopkins University

Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03787095     History of Changes
Other Study ID Numbers: ACTG A5370
38399 ( Registry Identifier: DAIDS-ES Registry Number )
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: July 16, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie results in the publication, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (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://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs