Clinical trial NCT06799650: Clinical Trial of Gammora® Plus Antiretroviral Treatment for HIV
Official title: Clinical Study to Evaluate the Efficacy and Safety of Gammora® in Addition to Standard Antiretroviral Treatment for HIV Infection in Antiretroviral Treatment-Naïve Participants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HIV Seropositivity
Keywords: HIV cure
integrase peptide
proviral HIV DNA
apoptosis
antiretroviral therapy
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
Collaborators: name: Code Pharma
First posted: 2025-01-29
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this phase II, open-label, randomized, controlled clinical trial is to evaluate the impact of Gammora®, a 16-mer HIV integrase-derived peptide associated with a boosted darunavir antiretroviral regimen compared Gammora® arm) to a boosted darunavir antiretroviral regimen only (control arm) in the estimated HIV reservoir among antiretroviral naïve people living with HIV. The main questions it aims to answer are:

1. Will the proviral (total) HIV-1 DNA decrease rapidly in the Gammora® arm compared to the control arm?
2. Will the apoptosis markers evaluated in the CD4+ T cell by flow cytometry increase in the Gammora® arm compared to the control arm? Forty antiretroviral naïve viremic people with HIV with CD4+ T cell counts \>350 cells/mL will be randomized to receive 20 mg of Gammora® in 2mL SC solution plus Tenofovir/3TC and Darunavir 800mg+Ritonavir 100mg (Gammora® arm) or antiretroviral only (control arm). In the Gammora® arm, participants had a 2-week Gammora® monotherapy lead-in period with Gammora® given daily before antiretroviral treatment is started, followed by 12 weeks of antiretroviral therapy plus Gammora® given every other day. The first two weeks of the trial (lead-in period for the Gammora® arm) were labeled w-2 and w-1 for both groups, and blood samples were collected for both groups. w0 denotes the week ART was started in both arms.


Eligibility criteria: Inclusion Criteria:

1. Confirmed HIV infection;
2. Antiretroviral naive;
3. HIV Viral load \> 1.000;
4. CD4+ T cell counts \>350 cells/mm3;
5. Body weight \> 50 Kg;
6. Signed informed consent form.

Exclusion Criteria:

1. BMI \< 18.5 kg/m2 at screening;
2. Coinfection with HBV (HBsAg +) or HCV;
3. Any significant acute illness within one week before the first visit.
4. Use of any immunomodulatory therapy (including interferon), systemic steroids, or systemic chemotherapy within four weeks before screening;
5. Active malignancy or malignancy in follow-up.
6. Changes in safety tests: neutrophil count \< 1,000 u/L; Hb \< 9.0 gm/dl; platelet count \< 75,000 u/L; creatinine \> 1.5 mg/dl, direct bilirubin \> 85 μmol/L, AST or ALT \> 2.5 X UNL;
7. Potential allergy or hypersensitivity to the components of the Gammora® formulation.
8. Participation in another clinical trial within 12 months before screening.
9. Any medical condition that makes the participant unsuitable for the study or increases the risk of participation at the investigator's discretion.

Primary outcomes:
measure: Total Proviral HIV DNA quantitation
timeFrame: Weekly from time of randomization for 27 consecutive weeks
measure: Episomal Proviral HIV DNA quantitation
timeFrame: Weekly from time of randomization for 27 consecutive weeks
measure: Apoptosis markers
timeFrame: Three times per week during from randomization to week 3 and weekly from that point through week 27
Secondary outcomes:
measure: HIV Viral load
timeFrame: Weekly from time of randomization for 27 consecutive weeks
measure: CD4 T cell counts
timeFrame: Weekly from time of randomization for 27 consecutive weeks
measure: CD8 T cell counts
timeFrame: Weekly from time of randomization for 27 consecutive weeks
measure: Levels of Lymphocyte T Cell activation markers (CD38 and HLA-DR in CD4 and CD8+ T cells) for each participant
timeFrame: Weekly for 12 weeks and every 4 weeks after that
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Weekly for 12 weeks and every 4 weeks after that
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: RDSS
state: SP
Study officials:
affiliation: Universidade Federal de São Paulo,
name: Ricardo S Diaz, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Levin A, Hayouka Z, Friedler A, Loyter A. Specific eradication of HIV-1 from infected cultured cells. AIDS Res Ther. 2010 Aug 19;7:31. doi: 10.1186/1742-6405-7-31.
citation: Levin A, Hayouka Z, Helfer M, Brack-Werner R, Friedler A, Loyter A. Peptides derived from HIV-1 integrase that bind Rev stimulate viral genome integration. PLoS One. 2009;4(1):e4155. doi: 10.1371/journal.pone.0004155. Epub 2009 Jan 7.
citation: Levin A, Hayouka Z, Helfer M, Brack-Werner R, Friedler A, Loyter A. Stimulation of the HIV-1 integrase enzymatic activity and cDNA integration by a peptide derived from the integrase protein. Biopolymers. 2010 Aug;93(8):740-51. doi: 10.1002/bip.21469.
citation: Rizza SA, Badley AD. HIV protease inhibitors impact on apoptosis. Med Chem. 2008 Jan;4(1):75-9. doi: 10.2174/157340608783331443.