Therapeutic vaccination: Phase I / II clinical study on patients randomized blinded to the experimental vaccine or placebo regimen. we want to evaluate the safety and the immunogenicity of a vaccine that includes a first administration of the ChAdOx1.tHIVconsvX product and a second one with MVA.tHIVconsvX in HIV-1 positive adults treated early and able to control the infection for a long time.

Phase 1

• Conditions: HIV infection; Therapeutic area: Diseases [C] - Virus Diseases [C02]; MedDRA version: 20.1Level: LLTClassification code 10008919Term: Chronic HIV infectionSystem Organ Class: 100000004862

• Registration Number: EUCTR2019-003102-26-IT
• Lead Sponsor: OSPEDALE SAN RAFFAELE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-07
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 33

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 < 50 copies/ml for at least 24 months
e.Stable ART regimen = 3 months

f.Willing and able to give written informed consent for participation in the study
g.Willing and able to adhere to an effective ART regimen for the duration of the study
h.CD4+ T cell count >= 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 < 1000 copies/ml; negative for hepatitis C antibodies OR confirmed clearance of HCV infection (spontaneous or following treatment); negative syphilis serology or documented adequate treatment of syphilis if positive EIA IgG or TPHA
l.Subjects with SARS-CoV-2 Asymptomatic or Pre-symptomatic Infection and Mild Illness (NIH COVID-19 Treatment Guidelines criteria - https://www.covid19treatmentguidelines.nih.gov). Volunteers will be enrolled following the current Italian Ministry of Health rules (https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2020&codLeg=76613&parte=1%20&serie=null): COVID-19 positive case without symptoms (CDC Asymptomatic Illness) can return to the community after a period of isolation of at least 10 days after the appearance of positivity, at the end of which a molecular test with negative result (10 days + test). COVID-19 positive case with symptoms (Mild Illness) may return to the community after a period of isolation of at least 10 days after the onset of symptoms (excluding anosmia and ageusia/dysgeusia that may have prolonged persistence over time) accompanied by a molecular test with negative result performed after at least 3 days without symptoms (10 days, of which at least 3 days without symptoms + test).
m.Available for follow up for duration of study and willing to comply with the protocol requirements
n.Women of child-bearing age must not be pregnant, not be planning a pregnancy or breast-feeding. Sexually active women must be willing to use an approved method of contraception from screening until 4 months after the second immunization. Sexually active men in heterosexual relationships must be willing to use an approved method of contraception with their partners from screening until 4 months after the second immunization.
o. Subjects with no immunization against COVID-19 or previous immunization with mRNA or protein vaccines (Moderna, Pfizer, Novavax) administered before the ChAdOx1.tHIVconsv1 vaccine;
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 33
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified