Clinical Trials

MainTitle

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

This study is ongoing, but not recruiting participants.
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator
Regeneron Pharmaceuticals

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03787095

First received: December 21, 2018
Last updated: November 5, 2019
Last Verified: November 2019
History of Changes
Purpose

Purpose

The purpose of this study is 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).

Condition Intervention Phase
HIV Infections

Biological : Cemiplimab
Biological : Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: 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 Participants With HIV-1 on Suppressive cART: A Phase I/II, Double-blind, Placebo-controlled, Ascending Multiple Dose Study

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Occurrence of a Grade 3 or higher adverse event (AE) related to study treatment (as judged by the Clinical Management Committee [CMC], 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
  • 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 CMC, 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:
  • 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
  • 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
  • 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
  • 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

Estimated Enrollment: 45
Study Start Date: April 8, 2019
Estimated Study Completion Date: December 8, 2021
Estimated Primary Completion Date: September 2, 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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

Admixture of Diluent for REGN2810 and 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

Admixture of Diluent for REGN2810 and 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

Admixture of Diluent for REGN2810 and sodium chloride for injection, administered as an IV infusion

Detailed Description:

This study will evaluate the safety and immunotherapeutic activity of an anti-PD-1 antibody (cemiplimab) in participants with HIV-1 on combination antiretroviral therapy (cART) who have plasma HIV-1 RNA <50 copies/mL and CD4+ T cell counts ≥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 only opening after all participants in the previous cohort have reached week 12 and an evaluation of safety outcomes has established that it is safe to dose escalate.
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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 70 Years  
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 ≥350 cells/mm^3
  • At least two plasma HIV-1 RNA <50 copies/mL 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 <50 copies/mL 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 ≥13.0 g/dL for men and ≥11.0 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
  • 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 - 70 years of age
  • Ability and willingness to provide informed consent.
  • Ability and willingness to continue non-study-provided 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
    • 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 ≥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.
    • Unstable asthma (e.g., sudden acute attacks occurring without an obvious trigger) or asthma requiring:
      • Daily steroid or long acting beta-agonist prevention
      • Hospitalization in the 2 years prior to entry
    • 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.
    • Any vaccination within 30 days
    • HCV treatment within 6 months
    • Prior immunoglobulin (IgG) therapy.
    • History of an adverse event related to prior administration of immunoglobulin therapy.
    • Current use or intent to use biotin ≥5 mg/day, including within dietary supplements.
    • 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.

    contacts and locations

    Contacts and Locations

    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, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT03787095

    Locations

    United States, Alabama
    Alabama CRS
    Birmingham, Alabama, United States, 35294
    United States, California
    UCSD Antiviral Research Center CRS
    San Diego, California, United States, 92103
    United States, North Carolina
    Chapel Hill CRS
    Chapel Hill, North Carolina, United States, 27599

    Sponsors and Collaborators

    National Institute of Allergy and Infectious Diseases (NIAID)
    Regeneron Pharmaceuticals

    Investigators

    Study Chair: Cynthia Gay, MD Chapel Hill CRS
    Study Chair: W. David Hardy, MD Johns Hopkins University
    More Information

    More 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  
    Study First Received: December 21, 2018  
    Last Updated: November 5, 2019  
    Individual Participant Data    
    Plan to Share IPD: Yes  

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

    Additional relevant MeSH terms:
    HIV Infections
    Cemiplimab
    Antibodies

    ClinicalTrials.gov processed this data on March 27, 2020
    This information is provided by ClinicalTrials.gov.