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HIV-1-infectionPhase 1ACTHIVE-001NCT03961438

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

A Phase 1 study testing ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes in people with HIV-1-infection, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
HIV-1-infection
What is being tested?
ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteNetherlands
Study dates
15 Nov 2019to 17 Apr 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
  • Any clinically relevant medical condition that is considered in the opinion of the investigator to make the volunteer unsuitable for participation in the study (under which underlying haematological disorders, auto-immune disease, immunodeficiency, gastrointestinal, hepatic and cardiopulmonary disorders). This also includes a history of malignancy in the past five years (prior to screening) or ongoing malignancy. (Note: A history of a completely excised malignancy that is considered cured is not an exclusion).
  • 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).
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  • 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.
  • Participation in another clinical trial of an Investigational Medicinal Product currently, within the previous three months or expected participation during this study. Concurrent participation in an observational study, not involving medicinal products and not requiring any blood or tissue sample collection is not an exclusion criterion.
  • 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).
  • Grade ≥ 1 clinically significant routine safety laboratory parameters.
  • If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • Amsterdam University Medical Centers, location AMC

    Amsterdam, North Holland, 1105AZ

Other trials in Netherlands

About this study

Official title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant HIV-1 Envelope Protein ConM SOSIP.v7 gp140 Vaccine, Adjuvanted With MPLA Liposomes, in Healthy, HIV-Uninfected Adults

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.

Read the detailed description

Human immunodeficiency virus (HIV) causes a global pandemic that affects nearly 37 million people and continues to spread at a rate of 1.8 million new infections annually. With currently only 21.7 million people on antiretroviral therapy (ART), a protective vaccine is crucial to reduce HIV spread and eliminate the pandemic. Given their protective capacity, a vaccine that induces neutralising antibodies (NAbs) against the HIV envelope protein (Env) would be a major step forwards. Nevertheless, the design of an effective NAb inducing vaccine has proven to be extremely challenging due to the instability and conformational flexibility of the trimeric Env protein. However, the development of stabilised, native-like trimeric Env proteins, termed SOSIP trimers, has revolutionised the HIV vaccine field by overcoming this obstacle.

The SOSIP prototype, BG505 SOSIP.664, was the first ever Env-based immunogen that consistently induced NAbs against neutralisation-resistant viruses in animals and BG505 trimer immunisation of non-human primates protected against BG505 virus acquisition. Yet, HIV-1 diversity is a major hurdle for generating broad protection by broadly neutralising antibodies (bNAbs). It is thought that consensus-based vaccines might be more amendable for driving neutralisation breadth, because consensus sequences contain less strain-specific antigenic determinants and are closer to individual viral strains than strains are to one another. Therefore, the native-like Env trimer ConM SOSIP.v7 gp140, used in this study, was modelled after the BG505 SOSIP.664 prototype, but based on a consensus sequence of all HIV-1 isolates in group M, responsible for the global HIV epidemic. Previous nonclinical studies in rabbits and non-human primates found the ConM SOSIP.v7 gp140 vaccine to be safe. Moreover, it induced remarkably strong autologous NAb responses and elicited modest levels of cross-neutralisation.

Bearing these promising results in mind, the investigators firstly aim to evaluate the safety and tolerability of the ConM SOSIP.v7 gp140 vaccine, adjuvanted with monophosphoryl lipid A (MPLA) liposomes, in healthy HIV-uninfected individuals. The secondary objective will be to determine whether the ConM SOSIP.v7 gp140 vaccine, adjuvanted in MPLA liposomes, is able to prime human germline (naive) B cells and drive antibody responses towards induction of NAb breadth.

The research will furthermore 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 bNAbs. It is thought that fractional dose boosting leads to competitive antigen binding in germinal centres, which results in selection and expansion of B cells with surface immunoglobulins showing the highest antigen affinity.

The immunological insights gleaned from this study will be crucial for further design refinement and clinical development. In-depth characterisation of the elicited immune response, accomplished for example by state-of-the-art 'omics techniques such as next generation sequencing (NGS) and transcriptomics, enables us to gain valuable information from just a few human trial subjects. As a part of the European AIDS Vaccine Initiative 2020 Consortium (EAVI2020), this study will aid with the objective to select and refine the best immunogens, adjuvants, prime-boost schedules and determine the impact of host factors such as gender and genetics, increasing the chance of discovery of a definitive vaccine, which most likely will be multi-component.

Conditions
HIV-1-infection
Being tested
ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes
Keywords
Neutralizing antibody responses, Antibodies, HIV-infection, Vaccine
Medical subject headings
Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomesBiological

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

    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.

  • ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomesBiological

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

    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 at months 0 and 2, and 20 μg at month 6. All immunogen dosages will be admixed with 500 μg MPLA formulated in liposomes.

Study groups in NCT03961438
Study groupRoleWhat they receive
Group AActive comparatorHIV-uninfected participants
Receives: Biological: ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes
Group BActive comparatorHIV-uninfected participants
Receives: Biological: ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events

    Proportion of volunteers with a ≥ grade 3 adverse event.

    Measured: 7 days post each vaccination

  2. Adverse events

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

    Measured: 28 days post each vaccination

  3. Vaccine-related serious adverse events

    Proportion of volunteers with vaccine-related serious adverse events.

    Measured: 18 months

Secondary outcomes (4)
  1. Autologous neutralising antibodies

    Serum titres of neutralising antibodies to virus expressing ConM envelope.

    Measured: 18 months

  2. Binding antibody responses

    Proportion and magnitude of the trimer binding antibody response.

    Measured: 18 months

  3. Heterologous neutralising antibodies

    Serum titres of neutralising antibodies against additional (Tier1a/b, Tier 2) HIV-1 virus strains.

    Measured: 18 months

  4. Env-specific B cell responses

    Measurement of the magnitude and phenotype of Env-specific plasmablast, naive, germinal centre and memory B cell responses in peripheral blood mononuclear cells (PBMC) and lymph node aspirates.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2019
  2. Study start15 Nov 2019
  3. Primary completion6 Jun 2022
  4. Study completion17 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03961438
Sponsor's protocol ID
NL69161.000.19
Acronym
ACTHIVE-001
Status last verified
Apr 2023
First submitted
22 May 2019
Last updated
21 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Results from this study will be disseminated locally and to the wider scientific community at conferences and in published open-access peer-reviewed journals, as appropriate. Any data used for publication will be fully anonymised. We plan to publish the data and hold onto the data for 20 years.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ConM SOSIP.v7 gp140, adjuvanted with MPLA liposomes in people with HIV-1-infection, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events (time frame: 7 days post each vaccination). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2023.

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