A Single Dose of Pembrolizumab in HIV-Infected People

NCT03367754 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18001318-CC-0013
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Human immunodeficiency virus (HIV) attacks the immune system. Some people with HIV have a low CD4+ T-cell count despite taking antiviral medicines that control HIV replication. These cells fight disease, so a low count makes it easier for people to become sick. Researchers want to see if a new drug can improve the immune system, including T cells. The drug is called pembrolizumab Objective: To see if pembrolizumab is safe to use in people with HIV who have a low CD4+ T cell count despite taking medicines that control HIV replication, and to see if it strengthens the immune system. Eligibility: People age 18 years or older with HIV who are taking antiretroviral drugs as treatment, have blood HIV levels below detection limits of commercial assays, and have a low CD4+ T-cell count (below 350 cells/mm3). Design: Participants will be screened with:

• Medical history
• Physical exam
• Heart, blood, and urine tests Sexually active participants must use 2 kinds of birth control. Participants will have leukapheresis. Blood will be removed through a needle in one arm. A machine will remove white blood cells. The rest of the blood will be returned into the other arm. Participants will have a baseline visit. They will have blood tests. They may have a pregnancy test. A needle will insert a thin plastic tube (IV) into an arm vein. The participants will get the study drug or a placebo through the IV for 30 minutes. They will be watched for a couple hours after. Participants will have 11 follow-up visits over the next 48 weeks. They will have a physical exam, vital signs, medical review, and blood tests. Participants may have another leukapheresis. Participants will be called every 12 weeks after their last follow-up visit to talk about how they feel and their health. Participation ends after the week 96 phone call.

Conditions

Human Immunodeficiency Virus

Keywords

Immunotherapy; Immunologic Non-Responder; Immunologic Response; Randomized; PD-1

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Either Grade 2 or Higher Autoimmune Events and Grade 3 or Higher Adverse Events

  Participants with either grade 2 or higher autoimmune events requiring corticosteroid therapy or grade 3 or higher adverse events that are possibly, probably, or definitely related to intervention. The severity of each adverse event was graded according to the "Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events". Grade 2: Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (eg, antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for ≤ 24 hrs. Grade 3: Prolonged (eg, not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death

  Up to 48 weeks from start of intervention

Study Arms (2)

Drug: Pembrolizumab

EXPERIMENTAL

Participants with HIV and CD4+ of 100-350 cells/mm\^3 received a single dose of Pembrolizumab 200 mg via intravenous (IV) infusion.

Drug: Pembrolizumab

Placebo

PLACEBO COMPARATOR

Participants with HIV and CD4+ of 100-350 cells/mm\^3 received a single dose of Placebo via intravenous (IV) infusion.

Other: Placebo

Interventions

Placebo OTHER

Single dose of Placebo given via intravenous (IV) infusion.

Placebo

Pembrolizumab DRUG

Pembrolizumab is a potent and highly selective humanized monoclonal antibody (immunoglobulin \[Ig\] G4 kappa isotype) that binds to PD-1, thus blocking the receptor from binding with its ligands. Single dose of Pembrolizumab 200 mg given via intravenous (IV) infusion.

Drug: Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals must meet all of the following criteria to be eligible for study participation:
• Greater than or equal to 18 years of age.
• Documented HIV-1 infection (eg, positive standard enzyme-linked immunosorbent assay or rapid HIV-1/HIV-2 antibody test with a confirmatory test such as western blot, or documentation of repeated HIV RNA of \> 1000 copies/mL). Outside documentation will be acceptable.
• Absolute neutrophil count \> 1000/microliter.
• Platelet count \> 125,000/microliter.
• Hemoglobin \> 10 g/dL.
• Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 1.1 times the upper limit of normal (ULN). Total bilirubin \< 1.1 x ULN (unless participant is taking atazanavir or has Gilbert syndrome).
• Calculated creatinine clearance (estimated glomerular filtration rate) greater than or equal to 60 mL/min/1.73 m2.
• Thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) within normal limits. If TSH is not within normal limits then the participant may be eligible if thyroxine (T4) is within normal limits. Participants will not be excluded if they are on a stable dose of replacement thyroid medication; dose may be adjusted as needed.
• No significant underlying pulmonary, cardiac, renal, or hepatic disease, as defined by a need for drug treatment or ongoing physician care.
• Under the care of a primary care physician.
• Willing to comply with study requirements and procedures including storage of biological specimens for future use in medical research.
• Willing to allow genetic testing.
• Able to provide informed consent.
• Participants of reproductive potential must agree to not become pregnant or to impregnate a partner beginning 30 days before the dose of pembrolizumab through 120 days post dose.

You may not qualify if:

• Females who are pregnant or breastfeeding.
• Has used an investigational drug agent or investigational device within 12 weeks of baseline.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Known allergy to any component of the pembrolizumab formulation.
• Systemic steroid therapy or other immunosuppressive therapy in the 3 months prior to enrollment (Inhaled or topical corticosteroids are permitted).
• Has used an immunotherapeutic agent within 6 months of baseline.
• Plans to receive any vaccine within 16 weeks of receiving pembrolizumab.
• Has active autoimmune disease or a history of autoimmune disease that has required systemic treatment (eg, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, T4) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has known active hepatitis B (HBV) or potential for HBV reactivation (eg, hepatitis B surface antigen \[HBS\] reactive, HBV DNA positive, or isolated anti-core antibody positive; individuals who are anti-HBS antibody positive with or without anti-core Ab are eligible).
• Has known active hepatitis C (HCV; eg, HCV RNA \[qualitative\] is detected). Patients who have sustained virologic response (SVR) to anti-HCV treatment are eligible if at least 24 weeks have passed since achieving SVR.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• History or other clinical evidence of:
• Significant or unstable cardiac disease
• Significant pulmonary disease

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health Clinical Center (CC): collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Gay CL, Bosch RJ, Ritz J, Hataye JM, Aga E, Tressler RL, Mason SW, Hwang CK, Grasela DM, Ray N, Cyktor JC, Coffin JM, Acosta EP, Koup RA, Mellors JW, Eron JJ; AIDS Clinical Trials 5326 Study Team. Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy. J Infect Dis. 2017 Jun 1;215(11):1725-1733. doi: 10.1093/infdis/jix191.

  PMID: 28431010 BACKGROUND

• Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, DePierres C, Mncube Z, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJ, Klenerman P, Ahmed R, Freeman GJ, Walker BD. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006 Sep 21;443(7109):350-4. doi: 10.1038/nature05115. Epub 2006 Aug 20.

  PMID: 16921384 BACKGROUND

• Henderson LJ, Reoma LB, Kovacs JA, Nath A. Advances toward Curing HIV-1 Infection in Tissue Reservoirs. J Virol. 2020 Jan 17;94(3):e00375-19. doi: 10.1128/JVI.00375-19. Print 2020 Jan 17.

  PMID: 31694954 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Study was terminated due to difficulty with participant recruitment

Results Point of Contact

• Title: Kovacs, Joseph
• Organization: Clinical Center

jkovacs@mail.nih.gov

+1 301 496 9907

Study Officials

• Joseph A Kovacs, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: December 11, 2017
• Study Start: August 6, 2018
• Primary Completion: December 17, 2021
• Study Completion: November 18, 2024
• Last Updated: January 17, 2025
• Results First Posted: January 17, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be shared at the time of publication.
• Access Criteria: Identified data in the Biomedical Translational Research Information System (BTRIS; automatic for activities in the CC).

Locations

US (1)