Safety and Immunogenicity Study of HIV-MAG Vaccine +/- IL-12 and Ad35-GRIN/ENV in HIV-uninfected Volunteers

A Phase 1 Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate Safety and Immunogenicity of a Multiantigen HIV (HIV-MAG) pDNA Vaccine With or Without Human IL-12 pDNA GENEVAX® IL-12) and Ad35-GRIN/ENV Vaccine in HIV-Uninfected, Healthy Volunteers

The purpose of this study is to evaluate the safety, tolerability and immunogenicity of multiantigen HIV (HIV-MAG) plasmid DNA (pDNA) vaccine co-administered with recombinant human IL-12 pDNA (GENEVAX® IL-12) followed or preceded by recombinant Ad35-GRIN/ENV HIV vaccine in low-risk for HIV-uninfected healthy adults.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: HIV-MAG (3,000mcg); Biological: Ad35-GRIN/ENV; Biological: GENEVAX® IL-12 (100mcg); Biological: GENEVAX® IL-12 (1000mcg)

Detailed Description

The study is a randomized, double-blind placebo-controlled trial assessing the safety and tolerability of HIV-MAG with or without co-administered GENEVAX® IL-12 given intramuscularly by in vivo electroporation (IM/EP) using the Ichor Medical Systems TriGrid Delivery System (TDS-IM) followed by Ad35-GRIN/ENV in each of four different regimens. An additional group will evaluate the safety and tolerability of Ad35-GRIN/ENV followed by HIV-MAG with co-administered GENEVAX® IL-12 given intramuscularly by in vivo electroporation (IM/EP) using the Ichor Medical Systems TriGrid Delivery System (TDS-IM).

Volunteers will be screened up to 42 days before the 1st vaccination and will be followed for 12 months after the first vaccine administration. It is anticipated that it will take approximately 3 months to enrol the study. Approximately 75 volunteers (60 vaccine/15 placebo recipients) will be included in the study.

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• Kenya
  • Nairobi, Kenya
    • Kenya AIDS Vaccine Initiative, Kangemi
• Rwanda
  • Kigali, Rwanda
    • Projet San Francisco
• Uganda
  • Entebbe, Uganda
    • Uganda Virus Research Institute-IAVI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy male or female adults,
• 18 to 50 years of age (21 to 50 years of age for volunteers in Rwanda),
• who do not report high-risk behaviour for HIV infection,
• who are available for the duration of the trial,
• who are willing to undergo HIV testing,
• use an effective method of contraception, and
• who, in the opinion of the principal investigator or designee, understand the study and who provide written informed consent.

Principal exclusion criteria:

• confirmed HIV infection,
• pregnancy and lactation,
• significant acute or chronic disease,
• clinically significant laboratory abnormalities,
• recent vaccination or receipt of a blood product,
• previous receipt of an HIV vaccine, and
• previous severe local or systemic reactions to vaccination or history of severe allergic reactions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: HIV-MAG followed by Ad35-GRIN/ENV; HIV-MAG (IM/EP) at Months 0,1,2 followed by Ad35-GRIN/ENV (IM) at Month 6. (Vaccine:Placebo = 12/3)	Biological: HIV-MAG (3,000mcg); Delivered intramuscularly by in vivo electroporation; Biological: Ad35-GRIN/ENV; (2x10^10vp) Delivered intramuscularly by standard needle injection
Experimental: Group 2: HIV-MAG+GENEVAX® IL-12 followed by Ad35-GRIN/ENV; HIV-MAG + GENEVAX® IL-12 (IM/EP) at Months 0,1,2 followed by Ad35-GRIN/ENV (IM) at Month 6. (Vaccine:Placebo=12/3)	Biological: HIV-MAG (3,000mcg); Delivered intramuscularly by in vivo electroporation; Biological: Ad35-GRIN/ENV; (2x10^10vp) Delivered intramuscularly by standard needle injection; Biological: GENEVAX® IL-12 (100mcg); Co-administered with HIV-MAG, delivered intramuscularly by in vivo electroporation
Experimental: Group 3: HIV-MAG+GENEVAX® IL-12 followed by Ad35-GRIN/ENV; HIV-MAG + GENEVAX® IL-12 (IM/EP) at Months 0,1,2 followed by Ad35-GRIN/ENV (IM) at Month 6. (Vaccine:Placebo= 12/3)	Biological: HIV-MAG (3,000mcg); Delivered intramuscularly by in vivo electroporation; Biological: Ad35-GRIN/ENV; (2x10^10vp) Delivered intramuscularly by standard needle injection; Biological: GENEVAX® IL-12 (1000mcg); Co-administered with HIV-MAG, delivered intramuscular by in vivo electroporation
Experimental: Group 4: HIV-MAG+GENEVAX® IL-12 followed by Ad35-GRIN/ENV; HIV-MAG + GENEVAX® IL-12 (IM/EP) at Month 0 followed by Ad35-GRIN/ENV (IM) at Month 4. (Vaccine:Placebo=12/3)	Biological: HIV-MAG (3,000mcg); Delivered intramuscularly by in vivo electroporation; Biological: Ad35-GRIN/ENV; (2x10^10vp) Delivered intramuscularly by standard needle injection; Biological: GENEVAX® IL-12 (1000mcg); Co-administered with HIV-MAG, delivered intramuscular by in vivo electroporation
Experimental: Group 5: Ad35-GRIN/ENV followed by HIV-MAG+GENEVAX® IL-12; Ad35-GRIN/ENV (IM) at Month 0 followed by HIV-MAG + GENEVAX® IL-12 (IM/EP) at Month 4. (Vaccine:Placebo=12/3)	Biological: HIV-MAG (3,000mcg); Delivered intramuscularly by in vivo electroporation; Biological: Ad35-GRIN/ENV; (2x10^10vp) Delivered intramuscularly by standard needle injection; Biological: GENEVAX® IL-12 (1000mcg); Co-administered with HIV-MAG, delivered intramuscular by in vivo electroporation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	To evaluate the safety and tolerability of HIV-MAG, GENEVAX® IL-12, and Ad35-GRIN/ENV administered in five heterologous prime-boost regimens.	13 months approximately

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	To assess (qualitative and quantitative) immune responses elicited by the different prime-boost regimens.	12 months

Collaborators and Investigators

• Sponsor: International AIDS Vaccine Initiative
• Collaborators: Auro Vaccines LLC; Ichor Medical Systems Incorporated

Publications and helpful links

General Publications

• Mpendo J, Mutua G, Nanvubya A, Anzala O, Nyombayire J, Karita E, Dally L, Hannaman D, Price M, Fast PE, Priddy F, Gelderblom HC, Hills NK. Acceptability and tolerability of repeated intramuscular electroporation of Multi-antigenic HIV (HIVMAG) DNA vaccine among healthy African participants in a phase 1 randomized controlled trial. PLoS One. 2020 May 29;15(5):e0233151. doi: 10.1371/journal.pone.0233151. eCollection 2020.
• Mpendo J, Mutua G, Nyombayire J, Ingabire R, Nanvubya A, Anzala O, Karita E, Hayes P, Kopycinski J, Dally L, Hannaman D, Egan MA, Eldridge JH, Syvertsen K, Lehrman J, Rasmussen B, Gilmour J, Cox JH, Fast PE, Schmidt C. A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults. PLoS One. 2015 Aug 7;10(8):e0134287. doi: 10.1371/journal.pone.0134287. eCollection 2015.

Helpful Links

• International AIDS Vaccine Initiative
• Ichor Medical Systems, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: December 19, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (Estimate): December 22, 2011

Study Record Updates

• Last Update Posted (Estimate): September 2, 2013
• Last Update Submitted That Met QC Criteria: August 30, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: HIV; HIV prevention; AIDS; HIV vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; Interleukin-12
• Other Study ID Numbers: IAVI B004