CClinicalTrials.gg
Sign In
TerminatedNCT03787095Updated Mar 2, 2022Results posted

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

A Phase 1/2 interventional study of Cemiplimab and Placebo in HIV Infections, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Terminated at 3 sites in United States. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2022-03-02.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Stopped by monitoring committee recommendation due to adverse events
Phase
Phase 1/2
Study type
Interventional
Enrollment
5
Allocation
Randomized
Ages
18 Years to 64 Years
Sex
All
01

Study 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).

Read the detailed description

This study evaluated 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 less than the quantification limit of an FDA-approved assay and CD4+ T cell counts ≥350/mm\^3.

Participants were planned to be enrolled into three sequential dose-rising cohorts. Participants in each cohort received infusions of either cemiplimab or placebo, with planned administration at study entry (Day 0) and Week 6, for a total of two infusions. All participants continued their non-study provided ART regimen. Enrollment in the second and third cohorts would only open after all participants in the previous cohort had reached week 12 and an evaluation of safety outcomes established that it is safe to dose escalate.

Participants had screening and pre-entry visits and attended study visits on Day 0 and Weeks 1, 2, 4, 6, 7, 8, 10, 12, 16, 20, 24, 28, 36, and 48. Participants were followed for 48 weeks.

Due to observed adverse events which were deemed possibly related to study treatment in two of four treated participants, the study was terminated and did not enroll further participants. The two participants who had adverse events did not receive the second infusion. The treated participants were followed for the planned 48 weeks, while the placebo participant was not followed after a final study visit at week 7.

02

Conditions studied

  • HIV Infections

Browse trials for

03

In context

HIV Infections

4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 5 is below the median of 83 across 3,251 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.

Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 64 Years
Sexes eligible
All
Accepts healthy volunteers
No

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 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
  • 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
  • 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 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 ≥50 kg (110 pounds)

Exclusion criteria

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.
  • 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.
  • 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.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Double (Participant, Care provider)
Enrollment
5 participants (actual)

Study arms

  • Experimental
    Cohort 1: Cemiplimab

    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

  • Placebo comparator
    Cohort 1: Placebo

    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

  • BiologicalCemiplimab

    Administered as an intravenous (IV) infusion

    Also known as: REGN2810

  • BiologicalPlacebo

    Diluent for REGN2810, administered as an IV infusion

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: Study Entry through Week 48 or premature discontinuation

  2. 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

    Time frame: Study Entry through Week 48 or premature discontinuation

Secondary outcomes

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

    Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.

    Time frame: Baseline through Week 12

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

    Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.

    Time frame: Baseline through Week 12

  3. 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

    Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Polyfunctional response was defined as being positive for two or more cytokines. Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.

    Time frame: Baseline through Week 12

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

    Change evaluated from baseline (average of pre-entry and entry measures) to after the first dose (average of Weeks 2-6), and from baseline to after the second dose (average of Weeks 8-12). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.

    Time frame: Baseline through Week 12

07

Results

Posted Dec 9, 2021
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.

Participant flow

The first participant was enrolled in August 2019. The final participant was enrolled in September 2019. The study was paused to accrual for emergency review by the study monitoring committee (SMC) in October 2019, followed by the decision to close the study later that month. Participants were recruited from 3 sites in the US.

Participant flow — Overall Study
MilestoneCohort 1: CemiplimabCohort 1: Placebo
Started41
Completed41
Not completed00

Outcome measures

PrimaryCount 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

Time frame:
Study Entry through Week 48 or premature discontinuation
Reported as:
Count of participants · Participants
Count of Participants With a Grade >=3 Adverse Event (AE) or Grade >=1 Immune-related AE (irAE) Related to Study Treatment
ParticipantsCohort 1: CemiplimabCohort 1: Placebo
Count of Participants With a Grade >=3 Adverse Event (AE) or Grade >=1 Immune-related AE (irAE) Related to Study Treatment20
PrimaryCount 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

Time frame:
Study Entry through Week 48 or premature discontinuation
Reported as:
Count of participants · Participants
Count of Participants With a Grade >=1 irAE Related to Study Treatment
ParticipantsCohort 1: CemiplimabCohort 1: Placebo
Count of Participants With a Grade >=1 irAE Related to Study Treatment20
SecondaryChange in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for CD107a and Interferon Gamma (IFNg) From Baseline to Post-baseline

Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.

Time frame:
Baseline through Week 12
Reported as:
Mean · Percentage of T cells
Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for CD107a and Interferon Gamma (IFNg) From Baseline to Post-baseline
Percentage of T cellsCohort 1: CemiplimabCohort 1: Placebo
Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for CD107a and Interferon Gamma (IFNg) From Baseline to Post-baseline0.01 ± 0.070.09 ± NA
Statistical analysis
  • Cohort 1: Cemiplimab · t-test, 2 sided · p = 0.71
SecondaryChange in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg or CD107a Alone From Baseline to Post-baseline

Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.

Time frame:
Baseline through Week 12
Reported as:
Mean · Percentage of T cells
Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg or CD107a Alone From Baseline to Post-baseline
Percentage of T cellsCohort 1: CemiplimabCohort 1: Placebo
Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg or CD107a Alone From Baseline to Post-baseline0.00 ± 0.702.52 ± NA
Statistical analysis
  • Cohort 1: Cemiplimab · t-test, 2 sided · p = 1.00
SecondaryChange 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

Change evaluated from baseline (average of pre-entry and entry measures) to post-baseline (average of weeks 2-12 measures). Polyfunctional response was defined as being positive for two or more cytokines. Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.

Time frame:
Baseline through Week 12
Reported as:
Mean · Percentage of T cells
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
Percentage of T cellsCohort 1: CemiplimabCohort 1: Placebo
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-baseline0.24 ± 0.42-0.86 ± NA
Statistical analysis
  • Cohort 1: Cemiplimab · t-test, 2 sided · p = 0.33
SecondaryChange in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg and CD107a After Each Infusion

Change evaluated from baseline (average of pre-entry and entry measures) to after the first dose (average of Weeks 2-6), and from baseline to after the second dose (average of Weeks 8-12). Results for each week are calculated by subtracting the corresponding background control value. If the result was less than zero after background subtraction, the result was set to zero.

Time frame:
Baseline through Week 12
Reported as:
Mean · Percentage of T cells
Change in HIV-1 Gag-specific CD8+ T Cells by Intracellular Staining for IFNg and CD107a After Each Infusion
Percentage of T cellsCohort 1: Cemiplimab
After first dose-0.01 ± 0.02
After second dose0.05 ± 0.20

Adverse events

Collected over Study entry through week 48 or premature discontinuation.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1: Cemiplimab0/4 (0%)1/4 (25%)4/4 (100%)
Cohort 1: Placebo0/1 (0%)0/1 (0%)1/1 (100%)
Most frequent serious events
Most frequent serious events
EventCohort 1: CemiplimabCohort 1: Placebo
ThyroiditisEndocrine disorders1/40/1
Blood thyroid stimulating hormone decreasedInvestigations1/40/1
Thyroxine increasedInvestigations1/40/1
Most frequent other events
Showing 10 of 20
Most frequent other events
EventCohort 1: CemiplimabCohort 1: Placebo
Alanine aminotransferase increasedInvestigations2/41/1
Aspartate aminotransferase increasedInvestigations2/41/1
Blood phosphorus decreasedInvestigations0/41/1
ProteinuriaRenal and urinary disorders2/40/1
RhinorrhoeaRespiratory, thoracic and mediastinal disorders2/40/1
Abdominal discomfortGastrointestinal disorders1/40/1
FatigueGeneral disorders1/40/1
Drug-induced liver injuryHepatobiliary disorders1/40/1
Upper respiratory tract infectionInfections and infestations1/40/1
Foot fractureInjury, poisoning and procedural complications1/40/1

Baseline characteristics

All participants

Age, Continuous
Age, Continuous(years)Cohort 1: CemiplimabCohort 1: PlaceboTotal
Median51 (39 to 54)52 (52 to 52)51 (50 to 52)
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1: CemiplimabCohort 1: PlaceboTotal
Female000
Male415
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort 1: CemiplimabCohort 1: PlaceboTotal
Hispanic or Latino112
Not Hispanic or Latino303
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort 1: CemiplimabCohort 1: PlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White404
More than one race011
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Cohort 1: CemiplimabCohort 1: PlaceboTotal
United States415
CD4 Count
CD4 Count(cells/mm^3)Cohort 1: CemiplimabCohort 1: PlaceboTotal
Median1151 (720 to 1674)348 (348 to 348)911 (528 to 1391)
CD8 Count
CD8 Count(cells/mm^3)Cohort 1: CemiplimabCohort 1: PlaceboTotal
Median1516 (1188 to 1872)286 (286 to 286)1508 (867 to 1524)
CD4/CD8 ratio
CD4/CD8 ratio(ratio)Cohort 1: CemiplimabCohort 1: PlaceboTotal
Median0.90 (0.62 to 0.98)1.22 (1.22 to 1.22)0.91 (0.88 to 1.05)

2 further baseline measures are reported on the registry.

08

Study locations

3 sites
  • Alabama CRS
    Birmingham, Alabama 35294, United States
  • UCSD Antiviral Research Center CRS
    San Diego, California 92103, United States
  • Chapel Hill CRS
    Chapel Hill, North Carolina 27599, United States
09

References and documents

Publications

  • 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. PubMed 33929394 ↗

Study documents

  • Study protocol · Nov 16, 2018
  • Statistical analysis plan · Sep 30, 2020
  • Informed consent form · Jan 2, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Individual participant data that underlie results in the publication, after deidentification.

Supporting information: Study protocol, Sap

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 2, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03787095
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Regeneron Pharmaceuticals
Responsible party
Sponsor
First posted
Dec 26, 2018
Start date
Aug 13, 2019
Primary completion
Aug 18, 2020
Completion
Aug 18, 2020
Results posted
Dec 9, 2021
Last update
Mar 2, 2022

Study contacts

Cynthia Gay, MD
study chair · Chapel Hill CRS
W. David Hardy, MD
study chair · Johns Hopkins University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Feb 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

HIV Infections→

Other studies from this sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Start the discussion