A Phase I, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Immunogenicity Study of Candidate HIV-1 Vaccines ChAdOx1.HTI and MVA.HTI With Recombinant HIV-1 Envelope Protein ConM SOSIP.v7 gp140 Vaccine, Adjuvanted With MPLA Liposomes in ART-Suppressed HIV-1 Positive Individuals

NCT05208125 | Completed Phase 1

• 1 other identifier: BCN03
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

BCN03 is a Single-site, randomized, double-blind, placebo-controlled, phase I study to evaluate the safety, tolerability, immunogenicity, and efficacy of a vaccine regimen that includes a sequence of the T- and B-cell immunogens ChAdOx1.HTI and MVA.HTI and ConM SOSIP.v7 gp140 adjuvanted with MPLA liposomes in 30 virologically-suppressed ART-treated HIV-1 positive individuals.

Conditions

HIV Infection

Keywords

Human immunodeficiency; Virus; Vaccine; HIV; Safety; Tolerability

Outcome Measures

Primary Outcomes (3)

• Local IMP-related AEs of Grade 3 and 4

  Proportion of participants that develop Grade 3 or 4 local IMP-related AEs, based on the DAIDS scale

  From first administration up to week 30 (i.e., start of ATI, 2 weeks after last administration).

• Systemic IMP-related AEs of Grade 3 and 4

  Proportion of participants that develop Grade 3 or 4 systemic IMP-related AEs, based on the DAIDS scale

  From first administration up to week 30 (i.e., start of ATI, 2 weeks after last administration).

• Descriptive of AEs

  Descriptive summary of any local and systemic AEs, including laboratory abnormalities, severity, durability, and relationship to IMP in vaccine recipients.

  From first administration up to week 30 (i.e., start of ATI, 2 weeks after last administration)

Secondary Outcomes (18)

• De novo T-cell Immunogenicity to HTI

  From week 0 to week 30

• Magnitude, focus and breadth of T-cell Immunogenicity to HTI

  From week 0 to week 30

• B-cell Immunogenicity (serum titers of NAbs)

  From week 0 to week 30

• B-cell Immunogenicity (proportion of NAbs)

  From week 0 to week 30

• B-cell Immunogenicity (magnitude of trimer binding antibodies)

  From week 0 to week 30

Study Arms (2)

CSSMS

EXPERIMENTAL

ChAdOx1.HTI at week 0, ConM SOSIP.v7 at weeks 4, 12 and 28, and MVA.HTI at week 22 (CSSMS).

Biological: ChAdOx1.HTI at week 0, ConM SOSIP.v7 at weeks 4, 12 and 28, and MVA.HTI at week 22 (CSSMS).

PPPPP

PLACEBO COMPARATOR

Normal saline solution at weeks 0, 4, 12, 22, and 28 (PPPPP).

Other: Normal saline solution

Interventions

ChAdOx1.HTI at week 0, ConM SOSIP.v7 at weeks 4, 12 and 28, and MVA.HTI at week 22 (CSSMS). BIOLOGICAL

Intramuscular administration of 1 x ChAdOx1.HTI (5x1010 Vp), 3 x ConM SOSIP.v7 (100μg) adjuvanted with MPLA liposomes (500μg), and 1 x MVA.HTI (2x108pfu)

CSSMS

Normal saline solution OTHER

Intramuscular administration of normal saline solution

PPPPP

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females aged at least 18 years on the day of screening and no greater than 60 years on the day of the first IMP administration.
• Confirmed HIV-1 infection.
• Optimal virological suppression for at least 2 years prior to the screening visit, defined as maintained pVL \<50 cop/ml allowing for isolated blips (non-consecutive 50-200 copies/mL)
• Being on the same ART regimen within at least 4 weeks prior to screening visit.
• CD4 count ≥ 500 cells/mm3 at the screening visit.
• Nadir CD4 count ≥ 350 cells/mm3. Lower counts at the moment of acute HIV-1 infection will be allowed only if appropriate immune recovery was followed after ART initiation and ART was not initiated within first 6 months after estimated time of HIV-1 acquisition.
• Willing and able to be adherent to their ART regimen for the duration of the study.
• Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
• In the opinion of the Principal Investigator or designee, the candidate has understood the information provided and capable of giving written Informed Consent.
• If heterosexually active female of childbearing potential(1), using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner(1) from 14 days prior to the first IMP administration and commit to use it until four months after the last IMP administration or until her pVL is \<50 copies/mL in two-consecutive determinations after ART resumption, whichever is later. All female candidates of childbearing potential who are not heterosexually active at screening, must agree to utilise an effective method of contraception if they become heterosexually active during the study.
• If heterosexually active male, regardless of reproductive potential, sterilized or agree on the use of an effective method of contraception by his female partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility(2) from the day of the first IMP administration until four months after the last IMP administration or until his pVL is \<50 copies/mL in two-consecutive determinations after ART resumption, whichever is later. All male candidates who are not heterosexually active at screening, must agree to utilise an effective method of contraception if they become heterosexually active during the study.
• Il female, willing to undergo urine pregnancy tests at the designated time points.
• Willing to accept blood draws and collect stool at time points specified in the Schedule of Events (Appendix VII).
• Willing to forgo donating blood, eggs, or sperm from the first IMP administration until four months after last IMP administration or until his or her pVL is \<50 copies/mL in two-consecutive determinations after ART resumption, whichever is later.
• (1) A woman will be considered of childbearing potential if not permanently sterilized nor postmenopausal. Permanent sterilization methods include tubal ligation, hysterectomy and bilateral oophorectomy. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.

You may not qualify if:

• If female, pregnant or planning a pregnancy during the study and until at least four months after the last IMP administration or until her pVL is \<50 copies/mL in two-consecutive determinations after ART resumption, whichever is later; or lactating.
• ART initiated within 6 months from the estimated time of HIV-1 acquisition documented by immediate ART initation after a) an HIV-1 documented seroconversion (\<180 days), b) an HIV-1 diagnose with negative or indeterminate western blot test or positive p24 antigenemia and/or c) presenting with symptoms suggestive of acute retroviral syndrome.
• When available, pre-ART genotypic data that demonstrates the presence of clinically significant drug resistance mutations that could prevent the construction of a viable ART regimen post-treatment interruption.
• Reported periods of suboptimal adherence to ART or suboptimal ART regimens (dual therapy allowed as switch-regimens if sustained viral uppression pVL\<50 copies/ml is documented).
• History of past ART interruptions longer than 2 weeks.
• Participation in another clinical trial that involves a treatment intervention (active arm) within 12 weeks of study entry (at screening visit).
• Any AIDS-defining disease or progression of HIV-related disease.
• History of autoimmune disease.
• History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study.
• Receipt of approved vaccines within 3 weeks of study entry(1)
• Known hypersensitivity to any component of the IMP formulation, or severe or multiple allergies to drugs or pharmaceutical agents.
• Previous immunisation with any experimental immunogens.
• Potential participant received or plans to receive:
• licensed live attenuated vaccines - within 28 days before or after planned administration of the first or subsequent study vaccinations. For details regarding COVID-19 vaccines, see bullet c and d below.
• other licensed (not live) vaccines - within 14 days before or after planned administration of the first or subsequent study vaccinations. For details regarding COVID-19 vaccines, see bullet c and d below.

Sponsors & Collaborators

• IrsiCaixa: lead
• José Moltó Marhuenda, PhD, MD: collaborator
• Beatriz Mothe Pujadas PhD,MD: collaborator
• Susana Benet Garrabé, PhD,MD: collaborator
• Lucía Bailón Álvarez, MD: collaborator

Study Sites (1)

Germans Trias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

MeSH Terms

Conditions

HIV Infections; Virus Diseases

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Upon preparation, masking of the study products will take place in the same preparation room.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive either the combined regimen with T- and B-cell immunogens (CSSMS) or placebo (PPPPP) in a double-blinded fashion at a ratio of 2:1.

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: January 26, 2022
• Study Start: March 30, 2022
• Primary Completion: March 30, 2022
• Study Completion: December 18, 2023
• Last Updated: May 7, 2024

Record last verified: 2024-05

Locations

ES (1)