PD-1 Inhibition to Determine CNS Reservoir of HIV-Infection

NCT03239899 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17014517-N-0145
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Background: HIV affects millions of people. The disease may "hide" in the brain, even in people with well-controlled HIV without cancer. Then it may "wake up" and continue. The drug pembrolizumab uses the body's immune system to fight cells like cancer cells. It is approved to treat some cancers but not HIV. Researchers want to see if it is safe for HIV-positive people without cancer. This study is not for HIV treatment; only one dose of the drug will be used. Objective: To learn if the drug pembrolizumab, used to treat certain cancers, is safe for HIV-positive people. Eligibility: Adults ages 18 and older with HIV who are in another NIH protocol Design: Participants will be screened with:

• Medical history
• Physical and neurological exams
• Blood tests
• Lumbar puncture. The lower back will be numbed. A needle will remove fluid from between back bones.
• FDG-PET/CT. A radioactive sugar will be injected in a thin plastic tube (catheter) inserted in an arm vein. Participants will rest for an hour, urinate, then lie in the scanner. A mask will hold the head still.
• Leukapheresis. An optional procedure at baseline. White blood cells are removed from you using a serum cell separator machine Women who can become pregnant cannot take pembrolizumab. Men who take it must use 2 kinds of contraception. Participants will have up to 7 more visits, which repeat some screening tests. At 1 visit, participants will get one dose of pembrolizumab by catheter for 30 minutes. They will get allergy and pain medicines. At 2 visits, participants will have a brain MRI. They will get a contrast agent by catheter. They will lie in a metal cylinder that takes pictures for 1-2 hours. They will get earplugs for loud sounds.

Conditions

HIV Infections

Keywords

HIV; Brain; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Frequency of Grade 3 or Higher Adverse Events

  The frequency of Grade 3 and higher Adverse Events (AEs) that are probably or definately causal to pembrolizumab was calculated for the duration of the study, i.e., up to 52 weeks following infusion of pembrolizumab.

  study duration (up to 52 weeks post infusion)

Secondary Outcomes (6)

• Change in HIV-specific Antibody Responses in the CSF and Serum Using LIPS Assay.

  3 weeks after infusion

• Change in CSF Cytokine Profile Post-study Drug

  3 weeks after infusion

• Peripheral CD4 Counts

  3 weeks after infusion

• HIV RNA in Plasma and CSF

  3 weeks after infusion

• Change in FDG-PET/CT Metabolic Uptake in CNS

  3 weeks after infusion

Study Arms (1)

HIV Participants

EXPERIMENTAL

Participants who received 200 mg of Pembrolizumab administered as a one-time intravenous infusion over 30 minutes during the treatment phase of the study.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Participants will receive one dose of 2mg/kg of pembrolizumab IV at Week 0.

HIV Participants

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Diagnosis of HIV-1 infection, with positive HIV 1 antibody testing
• HIV RNA less than or equal to 40 copies/mL in plasma in the last 12 or greater months
• CD4 count above 350 cells/uL
• Antiretroviral therapy for 12 months prior to trial
• Fully vaccinated against SARS-CoV-2. Fully vaccinated is defined as:
• Two weeks out from the second dose of a two-dose vaccine series (Moderna, Pfizer-BioNTech); or
• Two weeks out from a single-dose vaccine (Johnson \& Johnson/Janssen)
• Patient must be willing and able to comply with all the aspects of trial design and follow-up.
• Patients must be able to provide informed consent
• Women of childbearing potential must agree to use contraception (defined as two forms of effective birth control), from the time of enrollment until 4 months after the last exposure to pembrolizumab
• Participants who are physically able to father a child must agree to use 2 effective methods of contraception (birth control) from the time you enroll in the study until 4 months after your last exposure to pembrolizumab
• Effective methods of contraception for this study include:
• hormonal contraception (birth control pills, birth control patches, injected hormones, hormonal implants or vaginal ring),
• Intrauterine device,

You may not qualify if:

• Clinically significant medical disorders that might expose the patient to undue risk of harm confound study outcomes or prevent the patient from completing the study as identified on screening studies and by patient history. Examples of such conditions include known cardiac disease such as congestive heart failure, chronic obstructive pulmonary disease, uncontrolled hypertension, kidney disease, liver disease, endocrine disease, pulmonary disease, heart disease, progressive CNS disease such as Parkinson s disease, dementia, prior tuberculosis infection or ongoing CNS opportunistic infection.
• Patient has received immunomodulatory/immunosuppressive therapy (including IV steroids but excluding local injections) in the preceding 6 months.
• Patient with known autoimmunity that would include but is not limited to disorders such as hypo/hyperthyroidism, myasthenia gravis, diabetes mellitus type 1, hemolytic anemia, and immune mediated hepatitis (but excluding patients with hypothyroidism already on thyroid replacement therapy).
• Prior history of cancer (excluding non-invasive squamous and basal cell carcinoma)
• Any opportunistic infection in the prior 2 years (excluding thrush) including latent TB (or a positive TB Quantiferon Gold test)
• Patient has received other investigational drugs within 3 months before enrollment
• Positive serological or PCR evidence of active or prior infection with HTLV-1/II, Hepatitis B or C. Patients with hepatitis B core (+), surface antibody (+), surface antigen ( ) and hepatitis B DNA (-) eligible to participate in the study (provided they are on tenofovir, lamivudine or TAF). Participants with prior hepatitis C who are hepatitis C antibody (+) but hepatitis C RNA (-) with normal liver enzymes and no evidence of cirrhosis on clinical liver ultrasound are eligible to participate in the study.
• Metal in the body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or history of welding or metal worker
• Claustrophobia
• Inability to lie comfortably on the back for up to two hours.
• Abnormal anti-thyroid panel (anti-TPO and anti-TG) test at screening visit.
• AST and ALT values \>1.1 times ULN
• Fasting triglyceride \> 300 mg/dL
• Total bilirubin \>1.1 times ULN (unless participant is taking atazanavir or has Gilbert syndrome)
• Creatinine Clearance or eGFR \<60 ml/minute (adjusted for race)

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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

HIV Infections

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Avindra Nath, MD
• Organization: National Institutes of Health

avindra.nath@nih.gov

301-496-1561

Study Officials

• Avindra Nath, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 4, 2017
• Study Start: April 9, 2018
• Primary Completion: February 13, 2023
• Study Completion: February 13, 2023
• Last Updated: October 2, 2025
• Results First Posted: February 13, 2024

Record last verified: 2023-02-13

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Starting 6 months after publication, or at the time of publication
• Access Criteria: At request, through existing NIH technology transfer policy methods

Locations

US (1)