A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Ranging Doses of ALFQ Adjuvant in a Candidate HIV Vaccine Containing A244 and B.65321
Overview
- Phase
- Phase 1
- Intervention
- A244
- Conditions
- Human Immunodeficiency Virus (HIV)
- Sponsor
- U.S. Army Medical Research and Development Command
- Enrollment
- 65
- Locations
- 1
- Primary Endpoint
- Incidence of Adverse Events (AEs), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI), and unsolicited AEs
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
This study will evaluate the safety and tolerability (including reactogenicity) of candidate vaccine A244/B.63521 with Army Liposome Formulation (ALF) mixed with the saponin QS-21(Quillaja saponaria-21) (ALFQ) adjuvant. The purpose of this phase I randomized, double-blind clinical trial is to optimize vaccine adjuvant ALFQ dosing by assessing safety, reactogenicity, and immunogenicity. Safety and tolerability will be assessed with both clinical and laboratory monitoring. Sixty human immunodeficiency virus (HIV) negative participants will be enrolled to one of three arms. Vaccinations via intramuscular (IM) injection will occur at months 0, 1, and 2. All participants will receive A244 and B.63521 (300 micrograms of each). In addition, Arm 1 will receive 200 micrograms of ALFQ. Arm 2 will receive 100 micrograms of ALFQ. Arm 3 will receive 50 micrograms of ALFQ.
Detailed Description
The purpose of this Phase I randomized, double-blind clinical trial is to optimize ALFQ dosing. Safety will be assessed through the frequency of the overall and specific post-vaccination reactions. Blood will be collected to assess humoral, cell-mediated, and innate immune responses. Healthy adults not living with HIV who are available for 14 months will be enrolled. A total of 60 participants will be enrolled to one of three arms, each comprised of 20 candidate vaccine recipients. Each arm will receive identical doses of A244 and B.63521 (300 micrograms of each). In addition, Arm 1 will receive 200 micrograms of ALFQ. Arm 2 will receive 100 micrograms of ALFQ. Arm 3 will receive 50 micrograms of ALFQ. The safety, reactogenicity, and immunogenicity will then be compared among the three arms to determine the optimal dose of ALFQ. All vaccinations will be split into 2 half doses which will both be administered intramuscularly (IM) into the same deltoid muscle. Vaccinations will occur at months 0, 1, and 2. The second vaccination will be administered into the contralateral deltoid at study month 1 compared to the first vaccination at study month 0. The third vaccination at study month 2 will be administered into the same deltoid as the first vaccination at study month 0. Participants will be followed for 12 months following the last study vaccination. Safety and tolerability will be assessed with both clinical and laboratory monitoring. Vaccine- related reactions will be observed and solicited for 30 minutes post-vaccination and with the aid of a diary card and interview of participants during the 14 days post vaccination. The information gained from the review of the diary card and the interview with the participants will be documented in the clinical study chart. In addition, adverse events (AEs) will be documented at each clinical encounter. AEs will be graded for seriousness, severity, and relationship to the investigational product.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adults between the ages 18-55 years (inclusive)
- •Must be at low risk for HIV infection per investigator assessment and using the study risk assessment tool.
- •Able and willing to provide written, informed consent
- •Able and willing to comply with all research requirements, in the opinion of the Investigator
- •Agreement to refrain from blood donation during the course of the study
- •Minimum body weight of 110 pounds (lbs) (50kg)
- •Laboratory Criteria within 30 days before enrollment:
- •Hemoglobin ≥ 12.0 g/dL for women; ≥ 12.5 g/dL for men
- •White Blood Cell count = 3,500-10,800 cells/mm3
- •Platelets ≥140,000/mm3 and ≤ 450,000/mm3
Exclusion Criteria
- •Receipt of any investigational HIV vaccine or investigational adjuvant
- •Received an investigational product in the 30 days before enrollment, or planned to receive during the study period. This does not include products with emergency use authorization.
- •Concurrent participation in another clinical research study
- •Any serious medical illness or condition
- •Receipt of immunoglobulins or blood products within 3 months before enrollment
- •Any history of anaphylaxis or allergy to study product
- •History of sickle cell trait or disease
- •Pregnancy, lactation, or intention to become pregnant during the study
- •History of active/recent cancer still within treatment or active surveillance follow-up (except basal cell carcinoma of the skin and cervical carcinoma in situ). Treated/resolved cancers with no likelihood of recurrence may be deemed acceptable at Principal Investigator (PI) discretion.
- •History of autoimmune disease
Arms & Interventions
A244/B.63521 + 200 μg of ALFQ adjuvant
Arm 1: An injection containing 300 μg A244 plus 300 μg B.63521 with 200 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: A244
A244/B.63521 + 200 μg of ALFQ adjuvant
Arm 1: An injection containing 300 μg A244 plus 300 μg B.63521 with 200 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: B.63521
A244/B.63521 + 200 μg of ALFQ adjuvant
Arm 1: An injection containing 300 μg A244 plus 300 μg B.63521 with 200 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: 200μg ALFQ
A244/B.63521 + 100 μg of ALFQ adjuvant
Arm 2: An injection containing 300 μg A244 plus 300 μg B.63521 with 100 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: A244
A244/B.63521 + 100 μg of ALFQ adjuvant
Arm 2: An injection containing 300 μg A244 plus 300 μg B.63521 with 100 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: B.63521
A244/B.63521 + 100 μg of ALFQ adjuvant
Arm 2: An injection containing 300 μg A244 plus 300 μg B.63521 with 100 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: 100μg ALFQ
A244/B.63521 + 50 μg of ALFQ adjuvant
Arm 3: An injection containing 300 μg of A244 plus 300 μg B.63521 with 50 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: A244
A244/B.63521 + 50 μg of ALFQ adjuvant
Arm 3: An injection containing 300 μg of A244 plus 300 μg B.63521 with 50 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: B.63521
A244/B.63521 + 50 μg of ALFQ adjuvant
Arm 3: An injection containing 300 μg of A244 plus 300 μg B.63521 with 50 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).
Intervention: 50μg ALFQ
Outcomes
Primary Outcomes
Incidence of Adverse Events (AEs), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI), and unsolicited AEs
Time Frame: Days 0 to 393
The number of participants with AEs, SAEs, AESIs, and unsolicited AEs on Day 0 through Day 337 as assessed by the Division of AIDS (DAIDS) grading scale and possible attribution to Investigational Product. The number of participants with medically attended AE will be followed until Day 393.
Number of Participants with Local and Systemic Reactions
Time Frame: Days 0 to 14 post vaccination
Post-vaccination reactions, including redness/erythema, induration, pain/tenderness, itching, warmth, fever, chills, myalgia, arthralgia, headache, nausea, fatigue, rash, and dizziness, will be assessed and recorded on diary cards on Days 0 through 14.
Secondary Outcomes
- Number of Participants with HIV-specific Binding Antibodies(Day 0 to 336)