Evaluation of Safety and Immunogenicity of Ad26.Mos4.HIV and CH505 TF chTrimer Combination in Healthy Adults

Human Immunodeficiency Virus

This is a Phase I, randomized, double-blind, placebo-controlled clinical study to define the safety and immunogenicity resulting from a rapid dose-escalating vaccination schedule as compared to that of a co-administered, dose-consistent vaccination schedule. Participants randomized to receive vaccines will get either dose-consistent injections of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV or rapid, dose-escalating injections of CH505 TF chTrimer+ALFQ with an Ad26.Mos4.HIV prime, followed by dose-consistent injection of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV

This study is exploratory and will be a randomized, placebo-controlled, double-blind trial. A total of 78 healthy male and female participants, aged 18 to 50 years, who are at low risk for Human Immunodeficiency Virus (HIV) acquisition will be enrolled and randomized across four Arms (1a, 2a, 1b, and 2b). Enrollment will be completed in two parts, dubbed Part A and Part B. In Part A, up to 28 participants will be randomized across Arms 1a and 2a, with up to 14 participants per Arm. Within these Arms, participants will be randomized 11:3 to active vaccine versus placebo (normal saline) and followed for up to 18 months. In Part B, participants will be randomized across Arms 1b and 2b, with 25 individuals per Arm. Within these Arms, participants will be randomized 4:1 to active study vaccine versus placebo (normal saline) and followed for up to 18 months. All products will be administered by intramuscular (IM) injection into the same quadriceps muscle at each product administration visit. Participants randomized to receive active study vaccines in Arm 1a will receive dose-consistent injections of Ad26.Mos4.HIV (5x1010 viral particles \[vp\]/0.5 mL) and CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) co administered on Study Days 1 and 57, followed by a dose-consistent injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) on Day 169. Participants randomized to receive active study vaccines in Arm 2a will receive a lower dose of Ad26.Mos4.HIV (2.5x1010 vp/0.25 mL) and CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS 21) on Study Day 1, followed by rapid dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/25 µg QS 21) through Study Day 15, followed by injections of Ad26.Mos4.HIV (5x1010 vp/0.5 mL) and CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) on Study Day 57, followed by an injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) on Study Day 169. Participants randomized to receive active study vaccines in Arm 1b will have a similar dosing regimen as participants in Arm 1a but without Ad26.Mos4.HIV on Study Days 1 and 57. Participants randomized to receive active study vaccines in Arm 2b will have a similar dosing regimen as participants in Arm 2a but without Ad26.Mos4.HIV on Study Days 1 and 57. Enrollment into Arms 1a and 2a will be concurrent. Sentinel groups, comprised of the first eight participants enrolled across Arms 1a and 2a (4 participants per Arm; 3:1 active vaccine to placebo in each Arm), will be included to facilitate an assessment of the safety of the combination of products and vaccination regimens. For each sentinel group, the Safety Monitoring Committee (SMC) will review safety data, covering a period of 7 days post-injection, to determine if it is safe to continue enrollment in that Arm. For participants in Arm 1a, this includes safety data from immediately after the first study injection through Day 8. For participants in Arm 2a, this includes safety data from immediately after the first injection through Day 22 (i.e., through 7 days post-Day 15 injection). While Arm 1a and Arm 2a sentinel safety reviews can occur separately, safety data from both Arms will be considered. For Arms 1a and 2a, the remaining 20 participants (10 per Arm) will be enrolled at a rate of up to 3 participants per week (up to 2 in the first week after re-initiation of enrollment) only after the SMC confirms that it is safe to continue, and the Sponsor gives their approval to proceed. Enrollment in Part B (i.e., Arms 1b and 2b) will be initiated after enrollment in Part A (i.e., Arms 1a and 2a) has concluded, the SMC confirms that it is safe to continue after reviewing 7- or 21-days of post injection safety data from all Part A participants, and the Sponsor gives their approval to proceed. Part B enrollment will be similar to that in Part A, including concurrent enrollment into Arms 1b and 2b; the inclusion of sentinel groups, comprised of the first eight participants enrolled across Arms 1b and 2b (4 participants per Arm; 3:1 active vaccine to placebo in each Arm); and SMC review once 7- or 21-days of post-injection safety data is available from Arm 1b and 2b sentinel groups, respectively. Enrollment of the remaining 42 participants (21 per Arm) will occur only after the SMC confirms that it is safe to continue, and the Sponsor gives their approval to proceed. Enrollment in Part B will be restricted to a rate of up to 3 participants per week; however, the rate of enrollment may increase if, based on available safety data the risk to participants will not be negatively impacted, and only if approved by the Sponsor. Inguinal lymph node biopsies will be performed on Study Day 71 in a subset of participants from all four study Arms who provide consent for the optional procedure.

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