A Study to Assess the Safety and Immune Response to Env-C DNA and Protein Vaccines in Kenya

NCT04826094 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: RV46038608
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of HIV vaccines. A vaccine is a medical product given to prevent certain diseases. The vaccine may educate the body to form a defensive response to try to prevent the disease from the beginning, or preventing it from taking hold of the body. This defensive response is called the immune response. The experimental vaccines in this study are Env-C Plasmid DNA and HIV Env gp145 C690 protein, given with different adjuvants. An adjuvant is a substance added to vaccines that can help make the vaccine more effective by improving the immune response, or by causing the immune response to last longer than it would without the adjuvant. The adjuvants are mixed with the vaccines and injected into muscle or placed on top of the skin. The HIV vaccines contain a piece of genetic material or a protein copied drom the HIV virus cover (Env), but they do not contain the virus itself. The vaccines cannot cause HIV infection or Acquired Immune Deficiency Syndrome (AIDS). The purpose of this study is to find out if the study vaccines with adjuvants cause side effects and are tolerable, whether humans respond (develop immune responses) to the vaccines, and how ling the effects of the study vaccines last. The study will also compare the effects of the study vaccines with adjuvants and adjuvant patch to those of placebo injections and placebo patch. The placebo will consist of saline (sterile saltwater) and will look like study vaccines, be given in the same way, but will have no active vaccine or adjuvant in it. A total of 126 participants will take part in the study and each will have up to 26 clinic visits and will be followed-up for a total of 108 weeks.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (14)

• Number of Solicited Local Events Post Vaccination 1 by Priming Dose Group (Outcome 1)

  Incidence (number and percentage of participants) of local reactogenicity events post dose 1 by symptom, maximum severity, and priming dose group

  Day 1-Day 7 Post Vaccination 1

• Number of Solicited Local Events Post Vaccination 2 by Priming Dose Group (Outcome 2)

  Incidence (number and percentage of participants) of local reactogenicity events post dose 2 by symptom, maximum severity, and priming dose group

  Day 1-Day 7 Post Vaccination 2

• Number of Solicited Local Events Post Vaccination 3 by Priming Dose Group (Outcome 3)

  Incidence (number and percentage of participants) of local reactogenicity events post dose 3 by symptom, maximum severity, and vaccination group.

  Day 1-Day 7 Post Vaccination 3

• Number of Solicited Local Events Post Vaccination 4 by Vaccination Group (Outcome 4)

  Incidence (number and percentage of participants) of local reactogenicity events post dose 4 by symptom, maximum severity, and vaccination group

  Day 1-Day 7 Post Vaccination 4

• Number of Solicited Local Events Post Vaccination 5 by Vaccination Group (Outcome 5)

  Incidence (number and percentage of participants) of local reactogenicity events post dose 5 by symptom, maximum severity, and priming dose group

  Day 1-Day 7 Post Vaccination 5

• Number of Solicited Local Events Post Vaccination 6 by Vaccination Group (Outcome 6)

  Incidence (number and percentage of participants) of local reactogenicity events post dose 6 by symptom, maximum severity, and vaccination group

  Day 1-Day 7 Post Vaccination 6

• Number of Solicited Systemic Events Post Vaccination 1 by Priming Dose Group (Outcome 7)

  Incidence (number and percentage of participants) of systemic reactogenicity events post dose 1 by symptom, maximum severity, and priming dose group

  Day 1-Day 7 Post Vaccination 1

• Number of Solicited Systemic Events Post Vaccination 2 by Priming Dose Group (Outcome 8)

  Incidence (number and percentage of participants) of systemic reactogenicity events post dose 2 by symptom, maximum severity, and priming dose group

  Day 1-Day 7 Post Vaccination 2

• Number of Solicited Systemic Events Post Vaccination 3 by Priming Dose Group (Outcome 9)

  Incidence (number and percentage of participants) of systemic reactogenicity events post dose 3 by symptom, maximum severity, and vaccination group

  Day 1-Day 7 Post Vaccination 3

• Number of Solicited Systemic Events Post Vaccination 4 by Vaccination Group (Outcome 10)

  Incidence (number and percentage of participants) of systemic reactogenicity events post dose 4 by symptom, maximum severity, and vaccination group

  Day 1-Day 7 Post Vaccination 4

• Number of Solicited Systemic Events Post Vaccination 5 by Vaccination Group (Outcome 11)

  Incidence (number and percentage of participants) of systemic reactogenicity events post dose 5 by symptom, maximum severity, and priming dose group

  Day 1-Day 7 Post Vaccination 5

• Number of Solicited Systemic Events Post Vaccination 6 by Vaccination Group (Outcome 12)

  Incidence (number and percentage of participants) of systemic reactogenicity events post dose 6 by symptom, maximum severity, and vaccination group

  Day 1-Day 7 Post Vaccination 6

• Number of Related Unsolicited AEs (Outcome 13)

  Incidence (number and percentage of participants) of related unsolicited AEs by maximum severity and vaccination group.

  Day 1-Day 728

• Number of SAEs (Outcome 14)

  Incidence (number and percentage of participants) of SAEs by maximum severity and vaccination group

  Day 1-Day 728

Secondary Outcomes (11)

• Magnitude of Plasma IgG Binding Antibodies in Response to Differing DNA Priming Regimens

  Thru Week 105

• Durability of Plasma IgG Binding Antibodies in Response to Differing DNA Priming Regimens

  Thru Week 105

• Area Under the Curve (AUC) for Plasma IgG Binding Antibodies in Response to Differing DNA Priming Regimens

  Thru Week 105

• Magnitude of Plasma IgG Binding Antibodies Between Groups With and Without Rehydragel® After HIV Env gp145 C.6980 Protein Boosting

  Thru Week 105

• Durability of Plasma IgG Binding Antibodies Between Groups With and Without Rehydragel® After HIV Env gp145 C.6980 Protein Boosting

  Thru Week 105

Study Arms (8)

Group 1: Vaccine

EXPERIMENTAL

3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56

Biological: Env-C Plasmid DNA; Biological: HIV Env gp145 C.6980 protein; Drug: Rehydragel®; Drug: Placebo (IM)

Group 2: Vaccine

EXPERIMENTAL

3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56

Biological: Env-C Plasmid DNA; Biological: HIV Env gp145 C.6980 protein; Drug: Rehydragel®; Biological: ALF43; Drug: Placebo (IM)

Group 3: Vaccine

EXPERIMENTAL

3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56

Biological: Env-C Plasmid DNA; Biological: HIV Env gp145 C.6980 protein; Drug: Rehydragel®; Biological: dmLT; Drug: Placebo (IM); Drug: Placebo (TCl)

Group 4: Vaccine

EXPERIMENTAL

3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56

Biological: Env-C Plasmid DNA; Biological: HIV Env gp145 C.6980 protein; Drug: Rehydragel®; Biological: ALF43; Biological: dmLT; Drug: Placebo (IM); Drug: Placebo (TCl)

Group 5: Vaccine

EXPERIMENTAL

3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56

Biological: Env-C Plasmid DNA; Biological: HIV Env gp145 C.6980 protein; Drug: Rehydragel®; Biological: ALF43; Drug: Placebo (IM)

Group 6: Vaccine

EXPERIMENTAL

3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56

Biological: Env-C Plasmid DNA; Biological: HIV Env gp145 C.6980 protein; Drug: Rehydragel®; Biological: ALF43; Drug: Placebo (IM)

Group 7: Vaccine

EXPERIMENTAL

3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56

Biological: Env-C Plasmid DNA; Biological: HIV Env gp145 C.6980 protein; Drug: Rehydragel®; Biological: ALF43; Drug: Placebo (IM)

Pooled Placebo

PLACEBO COMPARATOR

Pooled placebo arm.

Drug: Placebo (TCl)

Interventions

Env-C Plasmid DNA BIOLOGICAL

2 mg per dose. Administered by intramuscular injection.

Group 1: Vaccine; Group 2: Vaccine; Group 3: Vaccine; Group 4: Vaccine; Group 5: Vaccine; Group 6: Vaccine; Group 7: Vaccine

HIV Env gp145 C.6980 protein BIOLOGICAL

100 µg per dose. Administered by intramuscular injection.

Group 1: Vaccine; Group 2: Vaccine; Group 3: Vaccine; Group 4: Vaccine; Group 5: Vaccine; Group 6: Vaccine; Group 7: Vaccine

Rehydragel® DRUG

Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection.

Group 1: Vaccine; Group 2: Vaccine; Group 3: Vaccine; Group 4: Vaccine; Group 5: Vaccine; Group 6: Vaccine; Group 7: Vaccine

ALF43 BIOLOGICAL

Adjuvant. Army Liposome Formulation-43% Cholesterol. 200 µg per dose. Administered by intramuscular injection.

Group 2: Vaccine; Group 4: Vaccine; Group 5: Vaccine; Group 6: Vaccine; Group 7: Vaccine

dmLT BIOLOGICAL

Adjuvant. Recombinant double mutant Escherichia coli heat labile toxin. 50 µg per dose. Transcutaneous application (needle-free skin patch). 1 mL diluted dmLT added to gauze pad at site of injection.

Group 3: Vaccine; Group 4: Vaccine

Placebo (IM) DRUG

0.9% sodium chloride (sterile saline). Administered by intramuscular injection.

Group 1: Vaccine; Group 2: Vaccine; Group 3: Vaccine; Group 4: Vaccine; Group 5: Vaccine; Group 6: Vaccine; Group 7: Vaccine

Placebo (TCl) DRUG

Transcutaneous application (needle-free skin patch). 0.9% sodium chloride (sterile saline) added to gauze pad at site of injection.

Group 3: Vaccine; Group 4: Vaccine; Pooled Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, male and female participant aged 18 to 40 years and available for 26 months.
• Must be at low risk for HIV infection per investigator assessment and using the study risk assessment tool.
• Must be able to understand and complete the informed consent process.
• Must be capable of reading English or Kiswahili.
• Must agree to a home visit.
• Must complete a Test of Understanding (TOU) before enrollment. Must answer 9 out of 10 questions correctly with a maximum of three attempts.
• Must be in good general health without a clinically significant medical history.
• HIV-uninfected per diagnostic algorithm within 45 days of enrollment.
• Laboratory values:
• Hemoglobin
• g/dL men
• g/dL women
• White Cell Count
• x 10³ cells/µL men
• x 10³ cells/µL women

You may not qualify if:

• A history of:
• Three or more sexual partners in the previous 24 weeks.
• Commercial sex work.
• Non-adherence to condom use in the absence of a long-term monogamous relationship.
• Intravenous drug use in the previous year.
• A sexually transmitted infection in the previous 24 weeks.
• Asplenia: any condition resulting in the absence of a functional spleen.
• Bleeding disorder diagnosed by a medical doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
• Breastfeeding or pregnant (positive pregnancy test) women or planning to become pregnant during the window between study enrollment and three months after the last vaccination visit.
• Any past, ongoing, or in remission history of treated or untreated autoimmune disease.
• Has known active Hepatitis B virus infection (or positive HBsAg).
• Has known active Hepatitis C infection.
• History of anaphylaxis or other serious adverse reaction to vaccines or allergies or reactions likely to be exacerbated by any component of the vaccine and placebo, including antibiotics or excipients.
• Absolute Neutrophil Count (ANC) \<1.0 x 10³ cells/µL.
• Participant has received any of the following substances:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Walter Reed Army Institute of Research (WRAIR): collaborator
• US Military HIV Research Program: collaborator
• The Emmes Company, LLC: collaborator

Study Sites (1)

Kenya Medical Research Institute/Walter Reed Project, Clinical Research Centre, Off Hospital Road

Kericho, Kenya

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

Results Point of Contact

• Title: David Fetterer, MS (Programmer Analyst)
• Organization: Henry M Jackson Foundation for the Advancement of Military Medicine

dfetterer@global-id.org

301.500.3818

Study Officials

• Josphat Kosgei, MBChB, MSc

  Kenya Medical Research Institute/US Medical Research Directorate-Africa

  PRINCIPAL INVESTIGATOR

• Christina Polyak, MD

  U.S. Military HIV Research Program (MHRP)/Walter Reed Army Institute of Research (WRAIR)

  STUDY CHAIR

• Sandhya Vasan, MD

  U.S. Military HIV Research Program (MHRP)/Walter Reed Army Institute of Research (WRAIR)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 1, 2021
• Study Start: March 15, 2021
• Primary Completion: February 13, 2024
• Study Completion: February 13, 2024
• Last Updated: March 26, 2025
• Results First Posted: March 26, 2025

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1)