Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Acute HIV Infection
- Registration Number
- NCT04505501
- Lead Sponsor
- Thai Red Cross AIDS Research Centre
- Brief Summary
Reducing HIV persistence in lymph nodes by Interleukin-15 (IL-15) Receptor super-agonist (N-803) in Individuals with Acute HIV Infection
- Detailed Description
This is a phase II, randomized, unblinded, controlled trial to investigate the safety, tolerability and immunomodulation effect of combining N-803 with ART during AHI. The study will be conducted at the Thai Red Cross AIDS Research Centre (TRCARC)/King Chulalongkorn Memorial Hospital and the Faculty of Medicine, Chulalongkorn University in Bangkok, Thailand.
Eligible participants will be asked to undergo LN Bx at baseline (untreated AHI), prior to initiating dolutegravir-based ART.
This study will have three steps.
In Step 1, N-803 will be administered subcutaneously at weeks 0, 3, 6 (total 3 doses) and will be initiated together with ART. Participants will be asked to undergo a second inguinal LN Bx on the opposite groin approximately at week 6 (no later than 1 week after completion of study agents). They will be followed for safety parameters at weeks 8 and 12, after which they will roll over to the RV412, WRAIR#2178 safety monitoring protocol. Step 1 duration for individual participants will be approximately 12 weeks. Step 1 has been completed as per protocol by 12 participants, 8 N-803 recipients and 4 ART only participants and study recruitment has ended.
In Step 2, participants who have completed Step 1 as per protocol and remain virologically controlled will be given a single dose of N-803 followed by ATI. The N-803 dose will be offered to all these participants regardless of initial randomization in Step 1. In Step 2, N-803 will be administered at Step 2 week 0 followed by ATI on the same day. The participants will be followed during ATI for viral rebound and monitored for the restart criteria for a maximum of 12 weeks. Participants who do not meet ART restart criteria at the end of Step 2 will proceed to RV412, WRAIR#2178 for safety follow-up.
In Step 3, participants who did restart ART during Step 2 will be monitored for safety after restarting ART. Participants will be monitored every 2 weeks for a total of 12 weeks in Step 3. Any participants who may not have achieved HIV suppression by the end of Step 3 and the study will also proceed to RV412, WRAIR#2178 for continuing safety follow-up. Total study duration through data analysis and closure is estimated at five years.
It is hypothesized that N-803 initiated with ART during AHI, will be safe, and will lead to a reduction of HIV reservoir size in LN, demonstrated by decreased frequencies of vRNA+ and vDNA+ cells in the LNs, in comparison with ART alone.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 14
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description N-803 N-803 Step 1: N-803 at 6mcg/kg every 3 weeks for 3 doses plus ART (n=10) Step 2 : N-803 at 6mcg/kg at week 0 single dose (n=8), ATI after N-803 injection until week 12 (If meet criteria to restart ART, participants will go to step 3). Step 3: ART restart (week 0 to week 12).
- Primary Outcome Measures
Name Time Method Rate of occurrence of ≥ grade 3 adverse events determined to be related (Safety) at time of study completion at week 12 Rate of occurrence of ≥ grade 3 adverse events determined to be related
Frequency of vRNA+ and vDNA+ cells and levels of vDNA and vRNA in LNs At baseline (week 0) and week 6 Frequency of vRNA+ and vDNA+ cells and levels of vDNA and vRNA in LNs
Frequency, phenotype and function of CD8+ T cells and innate cells in LNs At baseline (week 0) and week 6 Frequency, phenotype and function of CD8+ T cells and innate cells in LNs
Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI. viral rebound during Step 2 ATI Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI.
- Secondary Outcome Measures
Name Time Method Frequency, phenotype and function of NK, T, B and other immune cells in LNs and blood Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12 Frequency, phenotype and function of NK, T, B and other immune cells in LNs and blood
Viral load area under the curve (AUCv) during the 4 weeks after viral rebound Viral load area under the curve (AUCv)
Responses to pilot discrete choice experiment survey Step2 wk0 Describe participant preferences about participation in HIV remission trials with treatment interruptions
HIV-specific antibody levels and ADCC, ADCP, ADCVI activities Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12 HIV-specific antibody function as measured by Antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and Antibody-dependent cell-mediated viral inhibition (ADCVI) levels.
Frequency of cells harboring HIV-1 vDNA, vRNA, intact genome and replication competent HIV-1 in PBMC Step 1 weeks 0, 3, 6, 12; Step 2 week 0; Step 3 week 12 Frequency of cells harboring HIV-1 vDNA, vRNA, intact genome and replication competent HIV-1 in PBMC
Host and viral genes by transcriptome analysis Step 1 week 0 and 6 Host and viral genes by transcriptome analysis
Immune activation markers in blood Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12 Immune activation markers in blood
Immune activation markers in CSF Step 1 week 0, 6; Step 2 week 0; Step 3 week 0, 12 Immune activation markers in CSF
Extent of cerebral inflammation in MR Spectroscopy (MRS) Step 1 week 0, 6; Step 2 week 0; Step 3 week 0, 12 Extent of cerebral inflammation in MR Spectroscopy (MRS)
Trial Locations
- Locations (1)
Thai Red Cross AIDS Research Centre
🇹🇭Bangkok, Thailand