Summary

for people ages 18-70 (full criteria)
at San Diego, California and other locations
study started
estimated completion

Description

Summary

The purpose of this study is 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).

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

Details

This study will evaluate 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 HIV-1 RNA <50 copies/mL and CD4+ T cell counts ≥350/mm3.

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

Participants will attend study visits on Day 0 and Weeks 1, 2, 4, 6, 7, 8, 10, 12, 16, 20, 24, 28, 36, and 48. These visits may include a medical history, physical examination, urine and blood collection, and adherence assessments. Participants will be followed for 48 weeks.

Keywords

HIV Infections Cemiplimab Antibodies

Eligibility

You can join if…

Open to people ages 18-70

  • 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/mm3

  • At least two plasma HIV-1 RNA <50 copies/mL 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 <50 copies/mL within 90 days prior to study entry
  • The following laboratory values within 90 days prior to entry:
  • Absolute neutrophil count (ANC) ≥1500 cells/mm3

  • Hemoglobin ≥13.0 g/dL for men and ≥11.0 g/dL for women
  • Platelet count ≥150,000/mm3

  • 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
  • 18 - 70 years of age
  • 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
  • .
  • 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)

You CAN'T join if...

  • 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.
  • Unstable asthma (e.g., sudden acute attacks occurring without an obvious trigger) or asthma requiring:
  • Daily steroid or long acting beta-agonist prevention
  • Hospitalization in the 2 years prior to entry
  • 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.
  • History of an adverse event related to prior administration of immunoglobulin 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.

Locations

  • UCSD Antiviral Research Center CRS
    San Diego California 92103 United States
  • UCLA CARE Center CRS
    Los Angeles California 90035 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
ID
NCT03787095
Phase
Phase 1/2
Study Type
Interventional
Last Updated