HIV infection MedDRA version: 20.1 Level: LLT Classification code 10008919 Term: Chronic HIV infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: ChAdOx1.tHIVconsv1
Product Code: [C1]
Pharmaceutical Form: Solution for injection
Current Sponsor code: ChAdOx1.tHIVconsv1
Concentration unit: Other
Concentration type: not less then
Con
Sponsors
OSPEDALE SAN RAFFAELE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. Male or female, aged 18-60 years b. Confirmed HIV-1 seropositive documented c. ART commenced during primary HIV infection, as defined by Fiebig stage d. Plasma HIV-RNA = 500 cells/mm3 at screening i. No new AIDS-defining diagnosis or progression of HIV-related disease j. Haematological and biochemical laboratory parameters as follows: 1. Haemoglobin > 10g/dl 2. Platelets > 100.000/dl 3. ALT = 2.5 x ULN 4. Creatinine = 1.3 x ULN k. Serology: negative for hepatitis B surface antigen OR HbsAg positive with HBV DNA =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a. Confirmed HIV-2 seropositive b. Women who are pregnant or breastfeeding c. Participation in another clinical trial within 12 weeks of study entry d. Active or chronic hepatitis B virus infection, with detectable hepatitis B surface antigen, hepatitis B virus DNA, or both active and chronic hepatitis C virus infection, with detectable virus RNA, and syphilis e. History of systemic cancers, such as Kaposi’s sarcoma and lymphoma, or other virus-associated malignancies and/or history of AIDS-defining illness according to Centers for Disease Control and Prevention criteria f. Resistance to two or more classes of antiretroviral drugs g. History of cardiovascular event or at high risk of an event (eg, atherosclerotic cardiovascular disease score >15%) h. History of CD4+ T cell nadir <200 cells per µl during chronic stages of infection i. Advanced non-alcoholic fatty liver and advanced nonalcoholic steatohepatitis, if evidence for substantial fibrosis (fibrosis score =F2) or evidence of cirrhosis j. HIV-related kidney disease or moderate-to-severe decrease in estimated glomerular filtration rate (<45–60 ml/min/1·73 m²) k. History of autoimmune disease other than HIV-related auto-immune disease. l. History of HIV-associated dementia or progressive multifocal leukoencephalopathy and/or history or clinical manifestations of any physical or psychiatric disorder which could impair the subject’s ability to complete the study m. Seizure disorder or any history of prior seizure, history of syncope or fainting episodes within 12 months of study screening. n. History of anaphylaxis or severe adverse reaction to vaccines, allergy or hypersensitivity to latex. o. Unstable asthma (e.g. sudden acute attacks occurring without an obvious trigger) or asthma requiring: • Daily steroid or long acting beta-agonist prevention • Hospitalization in the last two years p. SARS-CoV-2 Moderate, Severe and Critical Illness (NIH COVID-19 Treatment Guidelines criteria: https://www.covid19treatmentguidelines.nih.gov). q. Previous immunization with Group E adenoviruses (i.e. ChAdOx1/ChAd63, AZD1222) within last 3 months. r. Previous immunisation with any experimental immunogens, current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents s. Any other prior therapy, which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the safety of vaccination with C1 in HIV-1 infected participants on cART with plasma HIV-1 RNA load (pVL) suppressed below the level of quantification.;Secondary Objective: Safety: •Evaluate the safety of vaccination with M3+M4 given as boost to C1 in HIV-1 infected participants on cART with pVL suppressed below the level of quantification. Vaccine immunogenicity: •Evaluate vaccine induced HIV-specific CD8+ T cell responses, in terms of magnitude and breath, as determined by IFN-gamma ELISPOT assay to vaccine sequences. •Evaluate vaccine induced T cell responses in controlling HIV-1 replication in vitro against a panel of HIV from major global clades. Viro-immunological assessment during ATI: •Evaluate the role of vaccination in controlling viral replication in HIV-1 infected participants who undergo ATI.;Primary end point(s): Proportion of participants who develop at least one = Grade 3 Adverse Event (AE) including local and systemic reactions, lab toxicities, and/or clinical events, that is possibly, probably or definitely related to study treatment any time from the first day of treatment through further 28 days following vaccination with C1.;Timepoint(s) of evaluation of this end point: At any time from the first day of treatment through further 28 days following vaccination with C1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety: - Proportion of participants who develop at least one = Grade 3 Adverse Event (AE) including signs/symptoms, lab toxicities, and/or clinical events, that is possibly, probably or definitely related to study treatment any time from the first day of treatment through further 28 days following vaccination with M3+M4 given as boost to C1. Vaccine Immunogenicity: - Evaluate vaccine immunogenicity as a proportion of volunteers responding to vaccination. - Relative change in magnitude of T-cell responses to HIV-1 conserved regions from pre-vaccination (Day 0) to post-vaccination at week 8 by IFN-y ELISPOT. - Change in breadth of T-cell responses targeting HIV conserved regions from pre-vaccination (Day 0) to post-vaccination at week 8 by IFN-y ELISPOT. - Relative change in HIV p24 levels in CD4+ T cells from pre-vaccination (Day 0) to post-vaccination at week 8 by Viral Inhibition Assay (VIA). Viro-immunological assessment during ATI: - Proportion of patients with pVL =1000 copies/mm3 at week 24. - Proportion of individuals in whom ART is reinitiated due to viral rebound (pVL =100,000 copies/ml or 2 consecutive pVL =10,000 copies/ml 7 days apart), >50% drop in CD4 cell counts, <350 cells/mm3 and/or symptomatic acute retroviral syndrome - Time to viral rebound during ATI. - Proportion of patients with low-level plasma viremia as measured by single copy assay after C1 vaccination and with booster M3+M4. - Change in total HIV DNA in CD4+ T cells at baseline, after vaccination and at ART re-initiation. - Proportion of patients with viral suppression 6 months after treatment resumption. - Proportion of patients with onset of new HIV-1 resistance as viral genotype to ART during ATI. - Proportion of patients with onset of vaccine-induced breakthrough viral gag and pol genes by sieve analysis at ART re-initiation. - Change in function and phenotype of HIV-1-specific T cell responses in participants from pre-vaccination (Day 0) to post-vaccinati | — |
Countries
Italy
Contacts
Public ContactUFFICIO PROTOCOLLI CLINICI
IRCCS OSPEDALE SAN RAFFAELE
Outcome results
None listed