RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV): Safety and Efficacy of Broadly Neutralizing Antibodies Combined With Therapeutic Vaccination for the Induction of HIV Remission
Overview
- Phase
- Phase 1
- Intervention
- VRC07-523LS
- Conditions
- HIV Infections
- Sponsor
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- To evaluate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination in PLWH who initiated ART during AHI.
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a phase I, randomized, double-blind, placebo-controlled clinical trial to investigate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62 prime, MVA.tHIVconsv4 and A244d11gp120/ALFQ vaccination, and the impact on viral load setpoint during analytic treatment interruption (ATI) in people living with human immunodeficiency virus-1 (HIV-1, PLWH) who have initiated or will initiate antiretroviral therapy (ART) during acute HIV-1 infection (AHI).
Detailed Description
This is a phase I, randomized, double-blinded, placebo-controlled clinical trial to investigate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.tHIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination, and the impact on viral load setpoint during ATI in PLWH who initiated ART during AHI. To evaluate the primary objectives, the study will enroll up to 40 adults already enrolled in the RV 254/WRAIR #1494 study who initiated ART during Fiebig I-V acute HIV-1 infection, with plasma HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks, CD4 T-cell counts ≥ 400 cells/mm3, viruses susceptible to VRC07-523LS and/or PGDM1400LS, and the absence of known protective HLA allele (Groups 1 and 2). Participants currently on ART who meet study entry criteria will be randomized (Section 6.2) in a 1:1 allocation to the Active (Group 1) or Comparator (Group 2) Arms prior to entering Step 1. To evaluate exploratory objectives, the study will also enroll up to 8 adults who are newly enrolled in the RV 254/WRAIR #1494 study, diagnosed during Fiebig I-V AHI, and have not yet initiated ART (Group 3).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Active Arm
Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20
Intervention: VRC07-523LS
Active Arm
Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20
Intervention: PGDM1400LS
Active Arm
Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20
Intervention: ChAdOx1.tHIVconsv1
Active Arm
Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20
Intervention: ChAdOx1.HIVconsv62
Active Arm
Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20
Intervention: MVA.tHIVconsv4
Active Arm
Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20
Intervention: A244d11 gp120
Active Arm
Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20
Intervention: ALFQ
Comparator Arm
Comparator Arm (Group 2) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20
Intervention: VRC07-523LS
Comparator Arm
Comparator Arm (Group 2) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20
Intervention: PGDM1400LS
Comparator Arm
Comparator Arm (Group 2) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20
Intervention: Placebo
Exploratory Arm
Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
Intervention: VRC07-523LS
Exploratory Arm
Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
Intervention: PGDM1400LS
Exploratory Arm
Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
Intervention: ChAdOx1.tHIVconsv1
Exploratory Arm
Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
Intervention: ChAdOx1.HIVconsv62
Exploratory Arm
Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
Intervention: MVA.tHIVconsv4
Exploratory Arm
Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
Intervention: A244d11 gp120
Exploratory Arm
Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
Intervention: ALFQ
Outcomes
Primary Outcomes
To evaluate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination in PLWH who initiated ART during AHI.
Time Frame: Measured from enrollment to a minimum of 50 weeks to a maximum of 100 weeks per participant
Occurrence of ≥ grade 3 AE or SAE that are possibly, probably, or definitely related to the IPs during the study
To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on viral load setpoint after viral rebound during ATI.
Time Frame: Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration)
Viral Load setpoint after 2 weeks post viral rebound during ATI.
Secondary Outcomes
- To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to first documented HIV-1 RNA viral rebound of ≥50 copies/mL following ATI.(Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration))
- To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on viral rebound dynamics during ATI.(Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration))
- To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI.(Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration))
- To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on total HIV-1 DNA levels prior to ATI(Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration))
- To assess the effects of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 specific cellular immune responses prior to ATI.(Measure during step 2: from the initial administration of bNab therapy through week 22 in arms 1 and 2 and through week 30 in arm 3.)
- To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the number of participants with plasma HIV-1 RNA < 1000 copies/mL at 12 and 24 weeks of(Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration))
- To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to ART resumption for an HIV-related (virologic, immunologic, or clinical) reason d(i. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration))
- To measure the effects of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 RNA levels while on ART.(Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration))
- To assess the effects of VRC07-523LS andPGDM1400LSin combination withChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62,MVA.tHIVconsv4 and A244d11 gp120/ALFQvaccination on HIV-1 specific humoral immuneresponses.(Measure at week 0 of Step 3 in all groups, just prior to ATI.)
- To assess the impact of VRC07-523LS andPGDM1400LS in combination withChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62,MVA.tHIVconsv4 and A244d11 gp120/ALFQvaccination on the HIV-1 reservoir prior to ATI(Measure at week 0 of Step 3 in all groups, just prior to ATI.)
- To characterize the pharmacokinetics of VRC07-523LS and PGDM1400LS.(Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration))
- To describe the neurological, neuroimaging andneuro-cognitive effects that occur after receiptof VRC07-523LS and PGDM1400LS incombination with ChAdOx1.tHIVconsv1,ChAdOx1.HIVconsv62, MVA.tHIVconsv4 andA244d11 gp120/ALFQ vaccination and ATI(Measure at week 0 of Step 3 in all groups, just prior to ATI.)
- To assess the effects of VRC07-523LS and PGDM1400LSin combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 specific humoral immune responses.(Measure at week 0 of Step 3 in all groups, just prior to ATI.)
- To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the HIV-1 reservoir prior to ATI(Measure at week 0 of Step 3 in all groups, just prior to ATI.)