Amsterdam UMC Clinical Trial With a Native-like HIV-1 Envelope Vaccine

NCT03961438 | Completed Phase 1

• 1 other identifier: NL69161.000.19
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

ACTHIVE-001 is a randomised, open-label, uncontrolled phase 1 clinical trial to determine the safety profile of the native-like HIV-1 envelope vaccine, ConM SOSIP.v7, adjuvanted with monophosphoryl lipid A (MPLA) liposomes. The study will furthermore determine the extent to which the vaccine influences the breadth of viruses neutralised by induced antibodies and the associated diversity of B and T cell responses. The research will also investigate the effect of a within-schedule successive dose level reduction (i.e. fractional dose boosting), aimed to induce higher levels of somatic hypermutation and broadly neutralising antibodies. The primary outcome will be measurement of adverse events. Secondary and exploratory outcomes will include specific viral neutralisation activity of serum antibodies and characterisation of antigen specific blood and lymph node B and T cell responses.

Conditions

HIV-1-infection

Keywords

Neutralizing antibody responses; Antibodies; HIV-infection; Vaccine

Outcome Measures

Primary Outcomes (3)

• Adverse events

  Proportion of volunteers with a ≥ grade 3 adverse event.

  7 days post each vaccination

• Adverse events

  Proportion of volunteers with ≥ grade 3 and/or vaccine related adverse events.

  28 days post each vaccination

• Vaccine-related serious adverse events

  Proportion of volunteers with vaccine-related serious adverse events.

  18 months

Secondary Outcomes (4)

• Autologous neutralising antibodies

  18 months

• Binding antibody responses

  18 months

• Heterologous neutralising antibodies

  18 months

• Env-specific B cell responses

  18 months

Other Outcomes (1)

• Env-specific T cell responses

  18 months

Study Arms (2)

Group A

ACTIVE COMPARATOR

HIV-uninfected participants

Biological: ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes

Group B

ACTIVE COMPARATOR

HIV-uninfected participants

Biological: ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes

Interventions

ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes BIOLOGICAL

Vaccine administration will be done at months 0, 2 and 6 by intramuscular injection into the deltoid muscle of the non-dominant arm. The immunogen will be used at the dosage of 100 μg and will be admixed with 500 μg MPLA formulated in liposomes.

Also known as: Recombinant HIV-1 trimeric gp140 Env protein: ConM SOSIP.v7.

Group A

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women, aged between 18 and 50 years on the day of screening.
• Willing to comply with the requirements of the protocol and available for follow-up for he planned duration of the study.
• Willing and able to give written informed consent.
• Willing to undergo HIV testing, risk reduction counselling and receive HIV test results, including the possibility of vaccine-induced seropositivity (VISP).
• All female individuals engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception for four months following Investigational Medicinal Product administration.
• All female volunteers who are not heterosexually active at screening, must agree to utilise an effective method of contraception if they become heterosexually active.
• All female volunteers must be willing to undergo urine pregnancy tests at designated time points.
• All sexually active male volunteers, regardless of reproductive potential, must be willing to use an effective method of contraception (such as consistent condom use) from the day of first vaccination until at least four months after the last vaccination to avoid exposure of partners to Investigational Medicinal Product in ejaculate and to prevent conception with female partners.
• Willing to abstain from donating blood, eggs or sperm from the day of first vaccination until at least 3 months after the end of their participation in the trial and, for those who test HIV-positive due to vaccine-induced antibodies, until the anti-HIV antibody titres become undetectable.
• All volunteers must be registered with a general practitioner.

You may not qualify if:

• Confirmed HIV-1 or HIV-2 infection (HIV Ag/Ab plus HIV RNA testing).
• Self-reported risk for HIV exposure or STIs prior to screening.
• If female, pregnant or planning a pregnancy during the period of enrolment until four months after the last study vaccination; or lactating.
• Infectious disease in the six months before screening: acute and chronic hepatitis B infection (HbsAg-positive), hepatitis C infection (anti-HCV and HCV RNA positive), treatment for chronic hepatitis C infection in the past year, or active syphilis (positive chemiluminescence immunoassay (LIAISON XL), confirmed by positive RPR).
• History of hyposplenia (anatomical or functional).
• Bleeding disorder that was diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions.) (Note: A volunteer who states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience, is eligible).
• Receipt of any vaccine within 60 days of vaccination with the Investigational Medicinal Product.
• Receipt of blood products or blood-derived products within four months of screening.
• Prior receipt of another investigational HIV vaccine or HIV monoclonal antibody (product). (Note: receipt of placebo in a previous HIV vaccine trial will not exclude a volunteer from participation if documentation is available.)
• Known hypersensitivity to any component of the vaccine formulation used in this trial, or severe or multiple allergies to drugs or pharmaceutical agents.
• Positive reaction in antinuclear antibody (ANA) screen and/or subsequent anti-dsDNA and/or anti-ENA assessment; or clinically significant immunoglobulin (IgA, IgG or IgM) values.
• Use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer. Use of corticosteroids, immunosuppressants, chemotherapeutics, anti-tuberculosis or other medications considered significant by the investigator within the previous six months. The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis (except for steroids applied to the non-dominant upper arm); or a short course (duration of ten days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least two weeks prior to enrolment in this study.
• Unable to read and speak Dutch or English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
• Active, serious infections requiring (par)enteral antibiotic, antiviral or antifungal therapy within 30 days prior to enrolment.
• Seizure disorder: A participant who has had a seizure in the last three years prior to screening is excluded. (Not excluded: a participant with a history of seizures who has neither required medications nor had a seizure for three years).

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam University Medical Centers, location AMC

Amsterdam, North Holland, 1105AZ, Netherlands

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

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

Study Officials

• Godelieve de Bree, MD, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Investigator

Model Details: Participants will be randomised in a 1:1 ratio between two treatment groups with a different dosing regimen. The randomisation will be stratified for gender.

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 23, 2019
• Study Start: November 15, 2019
• Primary Completion: June 6, 2022
• Study Completion: April 17, 2023
• Last Updated: April 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 18 months from when the study officially closes.
• Access Criteria: Directly from Dr. G.J. de Bree (g.j.debree@amsterdamumc.nl)

Locations

NL (1)