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HIV InfectionsPhase 1/2NCT03787095

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

A Phase 1/2 study testing Cemiplimab in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
HIV Infections
What is being tested?
Cemiplimab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
5 participants
Where
3 sitesUnited States
Study dates
13 Aug 2019to 18 Aug 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Alabama CRS

    Birmingham, Alabama, 35294

  • Chapel Hill CRS

    Chapel Hill, North Carolina, 27599

  • UCSD Antiviral Research Center CRS

    San Diego, California, 92103

Other trials in United States

About this study

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

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.

Conditions
HIV Infections
Being tested
Cemiplimab, Placebo
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CemiplimabBiological

    Also called REGN2810

    Administered as an intravenous (IV) infusion

  • PlaceboBiological

    Diluent for REGN2810, administered as an IV infusion

Study groups in NCT03787095
Study groupRoleWhat they receive
Cohort 1: CemiplimabExperimentalParticipants 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.
Receives: Biological: Cemiplimab
Cohort 1: PlaceboPlacebo comparatorParticipants received placebo, administered at Day 0 and Week 6 for a total of two infusions. Participants continued their current non-study provided ART regimen.
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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

    Measured: Study Entry through Week 48 or premature discontinuation

Secondary outcomes (4)
  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: Baseline through Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Dec 2018
  2. Study start13 Aug 2019
  3. Primary completion18 Aug 2020
  4. Study completion18 Aug 2020

Why it stopped: Stopped by monitoring committee recommendation due to adverse events

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03787095
Sponsor's protocol ID
ACTG A5370
Other IDs
38399
Status last verified
Feb 2022
First submitted
21 Dec 2018
Last updated
2 Mar 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie results in the publication, after deidentification.

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
  • 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.

    PubMed 38449916

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cemiplimab in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Count of Participants With a Grade >=3 Adverse Event (AE) or Grade >=1 Immune-related AE (irAE) Related to Study Treatment (time frame: Study Entry through Week 48 or premature discontinuation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03787095, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.

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