Safety and Immunogenicity of Clade C ALVAC and gp120 HIV Vaccine

• Register: ClinicalTrials.gov
• Last refreshed on: 25 March 2024
• Main ID: NCT03284710
• Date of registration: 13/09/2017
• Prospective Registration: No
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Safety and Immunogenicity of Clade C ALVAC and gp120 HIV Vaccine HVTN107
• Scientific title: A Phase 1/2a Partially Double-blinded, Randomized Clinical Trial to Characterize the Safety and Immunogenicity of Clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120 Alone, With MF59 Adjuvant, and With Alum Adjuvant in Healthy, HIV-uninfected Adult Participants
• Date of first enrolment: June 19, 2017
• Target sample size: 132
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03284710
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 1/Phase 2

Countries of recruitment

Mozambique, South Africa, Zimbabwe

Contacts

• Name: Paul Goepfert
• Affiliation: University of Alabama at Birmingham

• Name: Kathy Mngadi
• Affiliation: Centre for the AIDS Programme of Research in South Africa

Key inclusion & exclusion criteria

Inclusion Criteria:

General and Demographic Criteria

1. Age of 18 to 40 years

2. Access to a participating HVTN CRS and willingness to be followed for the planned
duration of the study

3. Ability and willingness to provide informed consent

4. Assessment of understanding: volunteer demonstrates understanding of this study;
completes a questionnaire prior to first vaccination with verbal demonstration of
understanding of all questionnaire items answered incorrectly

5. Agrees not to enroll in another study of an investigational research agent

6. Good general health as shown by medical history, physical exam, and screening
laboratory tests

HIV-Related Criteria:

7. Willingness to receive HIV test results

8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction
counseling.

9. Assessed by the clinic staff as being at "low risk" for HIV infection and committed to
maintaining behavior consistent with low risk of HIV exposure through the last
required protocol clinic visit.

Laboratory Inclusion Values

Hemogram/Complete blood count (CBC)

10. Hemoglobin = 11.0 g/dL for volunteers who were born female, = 13.0 g/dL for volunteers
who were born male

11. White blood cell count = 3,300 to 12,000 cells/mm^3

12. Total lymphocyte count = 800 cells/mm^3

13. Remaining differential either within institutional normal range or with site physician
approval

14. Platelets = 125,000 to 550,000/mm^3

Chemistry

15. Chemistry panel: ALT, AST, and ALP < 1.25 times the institutional upper limit of
normal; creatinine = institutional upper limit of normal.

Virology

16. Negative HIV-1 and -2 blood test: Sites may use locally available assays that have
been approved by HVTN Laboratory Operations.

17. Negative Hepatitis B surface antigen (HBsAg)

18. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase
chain reaction (PCR) if the anti-HCV is positive Urine

19. Normal urine:

- Negative urine glucose, and

- Negative or trace urine protein, and

- Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a
microscopic urinalysis with red blood cells levels within institutional normal
range).

Reproductive Status

20. Volunteers who were born female: negative serum or urine beta human chorionic
gonadotropin (ß-HCG) pregnancy test performed prior to vaccination on the day of
initial vaccination. Persons who are NOT of reproductive potential due to having
undergone total hysterectomy or bilateral oophorectomy (verified by medical records),
are not required to undergo pregnancy testing.

21. Reproductive status: A volunteer who was born female must:

- Agree to consistently use effective contraception for sexual activity that could
lead to pregnancy from at least 21 days prior to enrollment through the last
required protocol clinic visit. Effective contraception is defined as using
condoms (male or female), or diaphragm or cervical cap, PLUS 1 of the following
methods: Intrauterine device (IUD), Hormonal contraception (in accordance with
Republic of South Africa: National Contraception Clinical Guidelines), successful
vasectomy in the male partner (considered successful if a volunteer reports that
a male partner has [1] documentation of azoospermia by microscopy, or [2] a
vasectomy more than 2 years ago with no resultant pregnancy despite sexual
activity postvasectomy); or any other contraceptive method approved by the HVTN
107 Protocol Safety Review Team

- Or not be of reproductive potential, such as having reached menopause (no menses
for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal
ligation;

- Or be sexually abstinent.

22. Volunteers who were born female must also agree not to seek pregnancy through
alternative methods, such as artificial insemination or in vitro fertilization until
after the last required protocol clinic visit

Other

23. Volunteers who were born female consenting to provide cervical samples: pap smear
within the 3 years prior to enrollment, with the latest result reported as normal or
ASCUS (atypical squamous cells of undetermined significance); for those 21 years and
older that have not had a pap smear within the last 3 years prior to enrollment, must
be willing to undergo a pap smear with the result reported as normal or ASCUS prior to
sample collection.

Exclusion Criteria:

General

1. Blood products received within 120 days before first vaccination

2. Investigational research agents received within 30 days before first vaccination

3. Body mass index (BMI) = 40; or BMI = 35 with 2 or more of the following: systolic
blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known
hyperlipidemia

4. Intent to participate in another study of an investigational research agent or any
other study that requires non-HVTN HIV antibody testing during the planned duration of
the HVTN 107 study

5. Pregnant or breastfeeding

Vaccines and other Injections

6. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received
control/placebo in an HIV vaccine trial, the HVTN 107 PSRT will determine eligibility
on a case-by-case basis.

7. Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine
trial. Exceptions may be made for vaccines that have subsequently undergone licensure
in a volunteer's country of residence. For volunteers who have received
control/placebo in an experimental vaccine trial, the HVTN 107 PSRT will determine
eligibility on a case-by-case basis. For volunteers who have received an experimental
vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by
the HVTN 107 PSRT on a case-by-case basis.

8. Live attenuated vaccines other than influenza vaccine received within 30 days before
first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and
rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)

9. Influenza vaccine or any vaccines that are not live attenuated vaccines and were
received within 14 days prior to first vaccination (eg, tetanus, pne


Age minimum: 18 Years
Age maximum: 40 Years
Gender: All

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Biological: Bivalent Subtype C gp120

Biological: Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension

Biological: Bivalent Subtype C gp120/MF59

Biological: ALVAC-HIV (vCP2438)

Primary Outcome(s)

Level of Vaccine-induced Serum IgA Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 3 [Time Frame: Measured at Month 6.5]

Number of Participants Reporting New Chronic Conditions (Requiring Medical Intervention for >= 30 Days) [Time Frame: Measured through Month 18]

Number of Participants Reporting Serious Adverse Events (SAEs) [Time Frame: Measured through Month 18]

Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity [Time Frame: Measured through Month 18]

Level of Vaccine-induced Systemic IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 2 [Time Frame: Measured at Month 6.5]

Occurrence of Vaccine-induced Systemic IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 2 [Time Frame: Measured at Month 6.5]

Numbers of Participants With Grade 1 or Higher Local Laboratory Results [Time Frame: Measured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455]

Chemistry and Hematology Laboratory Measures - Lymphocytes, Neutrophils [Time Frame: Measured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455]

Number of Participants Reporting Adverse Events of Special Interest (AESIs) [Time Frame: Measured through Month 18]

Number of Participants With Early Study Termination Associated With an AE or Reactogenicity [Time Frame: Measured through Month 18]

Occurrence of Vaccine-induced Serum IgA Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 3 [Time Frame: Measured at Month 6.5]

Chemistry and Hematology Laboratory Measures - Creatinine [Time Frame: Measured during screening, Days 7, 42, 98, 182, 378, and 455]

Chemistry and Hematology Laboratory Measures - Hemoglobin [Time Frame: Measured during screening, Days 7, 42, 98, 182, 378, and 455]

Chemistry and Hematology Laboratory Measures - ALT (SGPT), AST, Alkaline Phosphatase [Time Frame: Measured during screening, Days 7, 42, 98, 182, 378, and 455]

Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product [Time Frame: Measured through 30 days after each vaccine dose at Months 0, 1, 3, 6, and 12]

Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration [Time Frame: Measured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12]

Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness [Time Frame: Measured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12]

Chemistry and Hematology Laboratory Measures - Platelets, WBC [Time Frame: Measured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455]

Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms [Time Frame: Measured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12]

Number of Participants Reporting Adverse Events (AEs), by Severity Grade [Time Frame: Measured through 30 days after each vaccine dose at Months 0, 1, 3, 6, and 12]

Secondary Outcome(s)

Level of Vaccine-induced Serum IgA Ab Binding to Env Proteins [Time Frame: Measured at Months 6.5 and 12.]

HIV-specific CD4+ T Cell Polyfunctionality by ICS - Functionality Scores [Time Frame: Measured at Months 6.5, 12, 12.5, and 18]

Occurrence of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins [Time Frame: Measured at Months 6.5 and 12.]

Occurrence of Vaccine-induced Serum IgG3 Ab Binding to Env Proteins [Time Frame: Measured at Months 6.5 and 12.]

HIV-specific CD4+ T Cell Polyfunctionality by ICS - Polyfunctionality Scores [Time Frame: Measured at Months 6.5, 12, 12.5, and 18]

Level of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins [Time Frame: Measured at Months 6.5 and 12.]

Occurrence of Vaccine-induced Serum IgA Ab Binding to Env Proteins [Time Frame: Measured at Months 6.5 and 12.]

Level of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) [Time Frame: Measured at Months 12.5 and 18.]

Occurrence of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins [Time Frame: Measured at Months 12.5 and 18.]

Occurrence of Vaccine-induced Serum IgG3 Ab Binding to Env Proteins [Time Frame: Measured at Months 12.5 and 18.]

Level of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) [Time Frame: Measured at Months 6.5 and 12.]

Level of Vaccine-induced Serum IgG3 Ab Binding to Env Proteins [Time Frame: Measured at Months 12.5 and 18.]

Level of Vaccine-induced Serum IgG3 Ab Binding to Env Proteins [Time Frame: Measured at Months 6.5 and 12.]

Level of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins [Time Frame: Measured at Months 12.5 and 18.]

Vaccine-induced Percentage of CD4+ T-cells Expressing Markers in Response to HIV Proteins Included in the Vaccine [Time Frame: Measured at Months 6.5, 12, 12.5, and 18]

Occurrence of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) [Time Frame: Measured at Months 12.5 and 18.]

Occurrence of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) [Time Frame: Measured at Months 6.5 and 12.]

Vaccine-induced Occurrence of CD4+ T-cells Expressing Markers in Response to HIV Proteins Included in the Vaccine [Time Frame: Measured at Months 6.5, 12, 12.5, and 18]

Secondary ID(s)

HVTN 107

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline

HIV Vaccine Trials Network

Sanofi Pasteur, a Sanofi Company

Results

• Results available: Yes
• Date Posted: 18/02/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03284710