Study of Boosting Strategies After Vaccination With ALVAC-HIV and AIDSVAX® B/E

NCT ID: NCT01931358

Last Updated: 2021-03-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-24
• Study Completion Date: 2021-12-31

Brief Summary

The primary purpose of the study is to better define the relative contributions of AIDSVAX® B/E alone, ALVAC-HIV alone, or ALVAC-HIV plus AIDSVAX® B/E combination to the observed immune profile in the weeks and months after receiving the original prime and boost vaccine regimen from study protocol RV 144, and their booster effects in both the systemic and mucosal compartments. In addition, this study will provide more intensive and comprehensive characterization of the innate, cell-mediated and humoral immune responses than possible within the RV 144 study.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Group Ia

ALVAC-HIV at Weeks 0 and 4; ALVAC-HIV + AIDSVAX B/E at Weeks 12 and 24

Group Type: EXPERIMENTAL

ALVAC-HIV

Intervention Type: BIOLOGICAL

1 mL intramuscular injection containing 10\^6 CCID50/dose

AIDSVAX B/E

Intervention Type: BIOLOGICAL

1 mL per injection (300 ug dose/antigen for a total of 600ug/dose administered)

Group Ib

ALVAC-HIV Placebo at Weeks 0 and 4; ALVAC-HIV Placebo + AIDSVAX B/E Placebo at Weeks 12 and 24

Group Type: PLACEBO_COMPARATOR

ALVAC-HIV Placebo

Intervention Type: BIOLOGICAL

1 mL per injection

AIDSVAX B/E Placebo

Intervention Type: BIOLOGICAL

1 mL per injection

Group IIa

ALVAC-HIV at Weeks 0 and 4; ALVAC-HIV + AIDSVAX B/E at Weeks 12, 24 and 48

Group Type: EXPERIMENTAL

ALVAC-HIV

Intervention Type: BIOLOGICAL

1 mL intramuscular injection containing 10\^6 CCID50/dose

AIDSVAX B/E

Intervention Type: BIOLOGICAL

1 mL per injection (300 ug dose/antigen for a total of 600ug/dose administered)

Group IIb

ALVAC-HIV Placebo at Weeks 0 and 4; ALVAC-HIV Placebo + AIDSVAX B/E Placebo at Weeks 12, 24 and 48

Group Type: PLACEBO_COMPARATOR

ALVAC-HIV Placebo

Intervention Type: BIOLOGICAL

1 mL per injection

AIDSVAX B/E Placebo

Intervention Type: BIOLOGICAL

1 mL per injection

Group IIIa

ALVAC-HIV at Weeks 0 and 4; ALVAC-HIV + AIDSVAX B/E at Weeks 12 and 24; AIDSVAX B/E at Week 48

Group Type: EXPERIMENTAL

ALVAC-HIV

Intervention Type: BIOLOGICAL

1 mL intramuscular injection containing 10\^6 CCID50/dose

AIDSVAX B/E

Intervention Type: BIOLOGICAL

1 mL per injection (300 ug dose/antigen for a total of 600ug/dose administered)

Group IIIb

ALVAC-HIV Placebo at Weeks 0 and 4; ALVAC-HIV Placebo + AIDSVAX B/E Placebo at Weeks 12 and 24; AIDSVAX B/E Placebo at Week 48

Group Type: PLACEBO_COMPARATOR

ALVAC-HIV Placebo

Intervention Type: BIOLOGICAL

1 mL per injection

AIDSVAX B/E Placebo

Intervention Type: BIOLOGICAL

1 mL per injection

Group IVa

ALVAC-HIV at Weeks 0, 4 and 48; ALVAC-HIV + AIDSVAX B/E at Weeks 12 and 24

Group Type: EXPERIMENTAL

ALVAC-HIV

Intervention Type: BIOLOGICAL

1 mL intramuscular injection containing 10\^6 CCID50/dose

AIDSVAX B/E

Intervention Type: BIOLOGICAL

1 mL per injection (300 ug dose/antigen for a total of 600ug/dose administered)

Group IVb

ALVAC-HIV Placebo at Weeks 0, 4 and 48; ALVAC-HIV Placebo + AIDSVAX B/E Placebo at Weeks 12 and 24

Group Type: PLACEBO_COMPARATOR

ALVAC-HIV Placebo

Intervention Type: BIOLOGICAL

1 mL per injection

AIDSVAX B/E Placebo

Intervention Type: BIOLOGICAL

1 mL per injection

Interventions

ALVAC-HIV

1 mL intramuscular injection containing 10\^6 CCID50/dose

Intervention Type: BIOLOGICAL

AIDSVAX B/E

1 mL per injection (300 ug dose/antigen for a total of 600ug/dose administered)

Intervention Type: BIOLOGICAL

ALVAC-HIV Placebo

1 mL per injection

Intervention Type: BIOLOGICAL

AIDSVAX B/E Placebo

1 mL per injection

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Healthy, HIV-uninfected male and female volunteers between age 20 and 40, weighing over 45 kilograms, and available for a period of 24 months and having a Thai identity card.

2. Must be at low risk for HIV infection per investigator assessment.

3. Must be able to understand and complete the informed consent process.

4. Must be capable of reading Thai.

5. Must successfully complete a Test of Understanding prior to enrollment.

6. Must be in good general health without clinically significant medical history.

7. HIV-uninfected per diagnostic algorithm within 45 days of enrollment.

8. Laboratory screening analysis:

• Hemoglobin: Women ≥12.0 g/dL, Men ≥12.5 g/dL
• White cell count: 4,000 to 11,000 cells/mm^3
• Platelets: 150,000 to 450,000/mm^3
• ALT and AST ≤1.25 institutional upper limit of reference range
• Creatinine: ≤1.25 institutional upper limit of reference range
• Urinalysis (dipstick) for blood and protein no greater than 1+ and negative glucose.

9. Female-Specific Criteria:

• Negative pregnancy test for women at screening and prior to each vaccination(same day)and prior to any of the invasive procedures.
• Be using adequate birth control methods for 45 days prior to the first vaccine/placebo vaccination and for at least 3 months after the final vaccine/placebo vaccination. Adequate birth control is defined as follows: Contraceptive medications delivered orally, intramuscularly, vaginally, or implanted, underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), condoms, diaphragms, intrauterine device (IUD), or abstinence.

Exclusion Criteria

1. Asplenia: any condition resulting in the absence of a functional spleen.

2. Bleeding disorder diagnosed by a medical doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).

3. Therapeutic anticoagulation resulting in an abnormal prothrombin (PT) / international normalized ration (INR) of partial prothrombin time (PTT).

4. Women breast-feeding or pregnant (positive pregnancy test) or planning to become pregnant during the window between study enrollment and 3 months after the last vaccination visit.

5. History of anaphylaxis or other serious adverse reaction to vaccines or allergies or reactions likely to be exacerbated by any component of the vaccine or placebo, including eggs, egg products, streptomycin, or neomycin.

6. Subject has received any of the following substances:

• Chronic use of therapies that may modify immune response, such as IV immuneglobulin and systemic corticosteroids (in doses of > 20 mg/day prednisone equivalent for periods exceeding 10 days). The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least 2 weeks prior to enrollment in this study.
• Blood products within 120 days prior to HIV screening.
• Immunoglobulins within 30 days prior to HIV screening.
• Any licensed vaccine within 14 days prior to initial study vaccine administration in the present study.
• Receipt of any investigational HIV vaccine.
• Investigational research agents or vaccine within 30 days prior to enrollment in the present study.
• Anti-tuberculosis prophylaxis or therapy during the past 90 days prior to enrollment.

7. Active sexually transmitted infection confirmed by clinical exam and diagnostic test.

8. Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contradiction to protocol compliance or impairs a subject's ability to give informed consent.

9. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within 5 years prior to enrollment, a history of suicide ideation or attempt.

10. Study site employees who are involved in the protocol and/or may have direct access to study related area.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Punnee Pitisuttithum, MD, DTM&H

Role: PRINCIPAL_INVESTIGATOR

Mahidol University

Locations

Royal Thai Army Clinical Research Center, AFRIMS

Bangkok, , Thailand

Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University

Bangkok, , Thailand

Research Institute for Health Sciences (RIHES), Chiang Mai University

Chiang Mai, , Thailand

Countries

Thailand

References

Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, Benenson M, Gurunathan S, Tartaglia J, McNeil JG, Francis DP, Stablein D, Birx DL, Chunsuttiwat S, Khamboonruang C, Thongcharoen P, Robb ML, Michael NL, Kunasol P, Kim JH; MOPH-TAVEG Investigators. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009 Dec 3;361(23):2209-20. doi: 10.1056/NEJMoa0908492. Epub 2009 Oct 20.

Reference Type: BACKGROUND

PMID: 19843557 (View on PubMed)

Rerks-Ngarm S, Paris RM, Chunsutthiwat S, Premsri N, Namwat C, Bowonwatanuwong C, Li SS, Kaewkungkal J, Trichavaroj R, Churikanont N, de Souza MS, Andrews C, Francis D, Adams E, Flores J, Gurunathan S, Tartaglia J, O'Connell RJ, Eamsila C, Nitayaphan S, Ngauy V, Thongcharoen P, Kunasol P, Michael NL, Robb ML, Gilbert PB, Kim JH. Extended evaluation of the virologic, immunologic, and clinical course of volunteers who acquired HIV-1 infection in a phase III vaccine trial of ALVAC-HIV and AIDSVAX B/E. J Infect Dis. 2013 Apr 15;207(8):1195-205. doi: 10.1093/infdis/jis478. Epub 2012 Jul 26.

Reference Type: BACKGROUND

PMID: 22837492 (View on PubMed)

Shubin Z, Stanfield-Oakley S, Puangkaew J, Pitisutthithum P, Nitayaphan S, Gurunathan S, Sinangil F, Chariyalertsak S, Phanuphak N, Ake JA, O'Connell RJ, Vasan S, Akapirat S, Eller MA, Ferrari G, Paquin-Proulx D; for the RV306 Study Group. Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability. AIDS. 2023 Aug 1;37(10):1519-1524. doi: 10.1097/QAD.0000000000003611. Epub 2023 Jun 1.

Reference Type: DERIVED

PMID: 37260254 (View on PubMed)

Pitisuttithum P, Nitayaphan S, Chariyalertsak S, Kaewkungwal J, Dawson P, Dhitavat J, Phonrat B, Akapirat S, Karasavvas N, Wieczorek L, Polonis V, Eller MA, Pegu P, Kim D, Schuetz A, Jongrakthaitae S, Zhou Y, Sinangil F, Phogat S, Diazgranados CA, Tartaglia J, Heger E, Smith K, Michael NL, Excler JL, Robb ML, Kim JH, O'Connell RJ, Vasan S; RV306 study group. Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial. Lancet HIV. 2020 Apr;7(4):e238-e248. doi: 10.1016/S2352-3018(19)30406-0. Epub 2020 Feb 6.

Reference Type: DERIVED

PMID: 32035516 (View on PubMed)

Other Identifiers

WRAIR 1920

Identifier Type: OTHER

Identifier Source: secondary_id

S-11-0002

Identifier Type: OTHER

Identifier Source: secondary_id

RV 306

Identifier Type: -

Identifier Source: org_study_id