Comparison of Dendritic Cell-Based Therapeutic Vaccine Strategies for HIV Functional Cure

NCT03758625 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: DAIDS-ES 38541U01AI131285
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This study will be done in people living with HIV to see if an investigational vaccine made from a person's own white blood cells is safe and tolerated. This study will also look at the body's immune response to the vaccine and evaluate four different methods of making the vaccine to see which method may result in better immune responses.

Conditions

HIV Infections

Keywords

dendritic cell; vaccine; immunogenicity; HIV; vaccination; immune system

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of six immunizations (10e7 DCs per dose) of DC-whole virus and DC-peptide vaccines in HIV-1 infected participants on effective ART

  Occurrence of Grade ≥ 3 AE including signs/symptoms, lab toxicities, and/or clinical events that are possibly, probably, or definitely related to study treatment (as judged by the site investigator, blinded to treatment arm) at any time from the initial dose of DC vaccine product to end of study follow-up.

  Step 2-Week 0 (overall Study Week 12) to overall Study Week 80

• Efficacy of six immunizations (10e7 DCs per dose) of DC-whole virus and DC-peptide vaccines in HIV-1 infected participants on effective ART

  Change in HIV-specific CD8 and T-cell immune response as measured by ELISPOT between the vaccine arms.

  Baseline to Step 2-Week 22 (overall Study Week 34)

Secondary Outcomes (6)

• Relative efficacy of the DC-HIV vaccines in priming HIV-specific-CD8+ T cells

  Baseline to Step 2-Week 22 (overall Study Week 34)

• Effect of DC-HIV vaccination on the level of persistent viremia in plasma

  Baseline to Step 2-Week 22 (overall Study Week 34)

• Effect of DC-HIV vaccination on HIV specific CD8 T-cell polyfunctional responses

  Baseline to Step 2-Week 22 (overall Study Week 34)

• Assess the impact of DC-HIV vaccination on levels of cell-associated HIV-1 RNA and DNA

  Baseline to Step 2-Week 22 (overall Study Week 34)

• Effect of DC-HIV vaccination on the levels of immune activation

  Baseline to Step 2-Week 22 (overall Study Week 34)

Study Arms (6)

ARM A

EXPERIMENTAL

a1DC + inactivated whole autologous HIV vaccine given as six monthly doses of approximately 10e7 DC per dose

Biological: a1DC + inactivated whole autologous HIV

ARM B

EXPERIMENTAL

a1DC + conserved HIV peptides vaccine given as six monthly doses of approximately 10e7 DC per dose

Biological: a1DC + conserved HIV peptides

ARM C

ACTIVE COMPARATOR

a1DC + no antigen vaccine given as six monthly doses of approximately 10e7 DC per dose

Biological: a1DC + no antigen

ARM D

EXPERIMENTAL

pgDC + inactivated whole autologous HIV vaccine given as six monthly doses of approximately 10e7 DC per dose

Biological: pgDC + inactivated whole autologous HIV

ARM E

EXPERIMENTAL

pgDC + conserved HIV peptides vaccine given as six monthly doses of approximately 10e7 DC per dose

Biological: pgDC + conserved HIV peptides

ARM F

ACTIVE COMPARATOR

pgDC + no antigen vaccine given as six monthly doses of approximately 10e7 DC per dose

Biological: pgDC + no antigen

Interventions

a1DC + inactivated whole autologous HIV BIOLOGICAL

Investigational vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) and loaded with autologous -inactivated HIV

ARM A

a1DC + conserved HIV peptides BIOLOGICAL

Investigational vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) and loaded with a conserved HIV gag and pol peptide pool

ARM B

a1DC + no antigen BIOLOGICAL

Control vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) but without an antigen

ARM C

pgDC + inactivated whole autologous HIV BIOLOGICAL

Investigational vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) and loaded with autologous -inactivated HIV

ARM D

pgDC + conserved HIV peptides BIOLOGICAL

Investigational vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) and loaded with a conserved HIV gag and pol peptide pool

ARM E

pgDC + no antigen BIOLOGICAL

Control vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) but without an antigen

ARM F

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by any FDA-approved assay. NOTE: The term 'licensed' refers to a US FDA approved kit, which is required for all investigational new drug (IND) studies.
• Receiving continuous ART for at least 24 months (defined as no interruptions longer than 14 consecutive days) and with no changes in the components of the ART for at least 8 weeks prior to study entry. A change in formulation (for example tenofovir disaproxil fumarate to tenofovir alafenamide) will not be considered a change in ART.
• Screening CD4+ cell count ≥350cells/mm3 obtained within 60 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent.
• Plasma HIV-1 RNA levels \< 50 copies/ml for at least 24 months prior to study entry using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent. Participants must have at least one documented HIV-1 RNA less than 50 copies/ml \>24 months prior to study entry and at least one HIV-1 RNA less than 50 copies/ml within 12 months prior to study entry. All available HIV-1 RNA measurements must be \< 50 copies/ml during the 24 months prior to study entry except as allowed by the following note.
• NOTE: Unconfirmed plasma HIV-1 RNA \> 50 copies/ml but \<200 copies/mL is allowed if followed by a subsequent value \< 50 copies/ml.
• Screening HIV-1 RNA levels \<50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 60 days prior to entry.
• Men and women age 18 to 70 years, inclusive.
• The following laboratory values obtained within 60 days prior to entry:
• Hemoglobin ≥10 g/dL Absolute neutrophil count (ANC) ≥1000/mm3 Platelet count ≥100,000/mm3 Creatinine ≤ 1.5x upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (SGPT) ≤2.5x ULN
• Ability and willingness of participant to provide informed consent.
• In the opinion of the investigator, no medical, mental health or other condition that precludes participation.
• For females of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point-of-care (POC)/ CLIA-waived test. Females of reproductive potential include women who have not been post-menopausal for at least 12 consecutive months, (i.e., who have had menses within the preceding 12 months) or women who have not undergone surgical sterilization (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation or salpingectomy). Self- report is acceptable documentation of menopause and sterilization.
• All participants must agree not to participate in the conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the participant/partner must use at least one reliable form of contraception (condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an IUD; or hormone-based contraceptive), while receiving study treatment and for 12 weeks following the final study vaccine.

You may not qualify if:

• Currently breastfeeding or pregnant
• Known allergy/sensitivity or any hypersensitivity to components of study vaccine or their formulation.
• Known chronic inflammatory conditions such as, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis), chronic pancreatitis, or autoimmune hepatitis, myositis, or myopathy.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Serious medical illness that requires systemic treatment and/or hospitalization within 30 days prior to entry.
• Use of systemic immunomodulators (eg, interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry.
• NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as the equivalent of prednisone ≤10 mg/day, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids, or topical imiquimod will not be excluded.
• Participation on any HIV immunotherapy or therapeutic vaccination trials within 6 months prior to study entry.
• History of positive HCV antibody with detectable HCV RNA in plasma within 48 weeks prior to study entry.
• NOTE: Persons with positive HCV Ab but negative plasma HCV RNA are allowed to participate. Sites must document negative HCV RNA within 24 weeks of study entry.
• History of positive HBsAg within 48 weeks prior to study entry.
• Treatment for hepatitis C within 6 months prior to study entry.
• Initiation of ART during acute HIV-1 infection (as determined by the site investigator by history and/or available medical records).
• Lack of adequate venous access that, in the opinion of the investigator, would interfere with study requirements.

Sponsors & Collaborators

• Sharon Riddler: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

AIDS Clinical Trials Unit/The Ohio State University

Columbus, Ohio, 43210, United States

Location

HIV/AIDS Clinical Research Unit / University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

HIV Infections

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

Study Officials

• Sharon Riddler, MD

  University of Pittsburgh

  STUDY CHAIR

• Bernard Macatangay, MD

  University of Pittsburgh

  STUDY CHAIR

• John Mellors, MD

  University of Pittsburgh

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, double-blind, multi-arm

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 29, 2018
• Study Start: January 2, 2019
• Primary Completion: February 19, 2025
• Study Completion: February 19, 2025
• Last Updated: October 29, 2025

Record last verified: 2025-10

Locations

US (2)