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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

17-N-0145

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

HIV;
Brain;
Immunotherapy

Recruitment Keyword(s)

None

Condition(s)

HIV Infections

Investigational Drug(s)

Pembrolizuma

Investigational Device(s)

None

Intervention(s)

Drug: Pembrolizumab

Supporting Site

National Institute of Neurological Disorders and Stroke

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.

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.

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Eligibility

INCLUSION CRITERIA:

-18 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

-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

-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,

---Barrier methods (condom or diaphragm) combined with spermicide, and

---Surgical sterilization (hysterectomy, tubal ligation, or vasectomy).

---If you have had a hysterectomy, tubal ligation, or vasectomy (or have a partner with a hysterectomy, tubal ligation or vasectomy), you do not have to use 2 methods of birth control.

EXCLUSION CRITERIA:

-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.

-Female sex of reproductive potential (this does not include women who are menopausal, post-hysterectomy, post-tubal ligation, or other methods of sterilization/inability to reproduce)

-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 will be 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 screening/baseline blood tests exceeding any of the limits defined below or as deemed exclusionary by the investigators on review:

--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)

--Hemoglobin < 10 g/dL

--Absolute neutrophil count < 1000/microliter

--Platelet count <100,000/mm(3) (if platelet clumping is present on hematology slide review, platelet count <100,000/mm3 will be considered exclusionary to study)

--Hemoglobin A1c greater than or equal to 6%

--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.

-An employee or staff of the NIH


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Citations:

Dahl V, Peterson J, Fuchs D, Gisslen M, Palmer S, Price RW. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation. AIDS. 2014 Sep 24;28(15):2251-8. doi: 10.1097/QAD.0000000000000400.

Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006 Feb 9;439(7077):682-7. Epub 2005 Dec 28.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Avindra Nath, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)



Avindra Nath, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
BG 10 RM 7C103
10 CENTER DR
BETHESDA MD 20814
(301) 496-1561
natha@mail.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03239899

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