A randomised phase II placebo-controlled trial of ART plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) vs ART plus placebo during primary HIV-1 infection to study the impact on post-treatment HIV control

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ANRS Maladies Infectieuses Emergentes

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

11 Apr 2024 → ongoing

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ANRS MIE

External identifiers

EU CT number

2024-516150-22-00

EudraCT number

2021-003040-25

ClinicalTrials.gov

NCT05300035

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

Evaluate if the administration of a treatment consisting of dual long-acting HIV-specific broadly neutralizing antibodies (3BNC117-LS & 10-1074-LS (bNAbs)), in combination with an antiretroviral therapy (ART) in individuals with primary HIV-1 infection (PI) when compared to ART only (with neutralizing antibodies or placebo) will favour a period of HIV-1 remission when ART is interrupted 52 or 76 weeks later.

Secondary objectives 4

1. Evaluate the tolerability of intravenous (IV) infusion of bNAbs
2. After bNAbs infusions and during ART, during analytic treatment interruption (ATI) and after ART resumption for non-controller participants: o clinical, immunological and virological changes from baseline, o activation and inflammatory markers changes from baseline, o changes from baseline in the persistent viral reservoir
3. Baseline factors associated with plasma Viral Load (VL) control during ATI
4. To explore: o expectations and motivations related to participation in the clinical trial and their evolution after having experienced such a participation, o anticipation and understanding of risks and benefits related to participation, o evolution over time of participation experience and of satisfaction with the information delivered, o experience and perception of the ATI period, with an emphasis on its impact on prevention behaviours and sexual quality of life, o reasons and experience related to refusal of participation.

Conditions and MedDRA coding

HIV

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant with confirmed primary HIV-1 infection (PI) diagnostic, symptomatic or asymptomatic, corresponding to one of the situations bellow: o Negative ELISA test (non-dissociated test) or ELISA Ac-/p24- and positive HIV-1 RNA (confirmed by a second positive HIV-1 RNA), o ELISA test Ac-/p24+ (confirmed by a positive HIV-1 RNA), o Positive ELISA test (non-dissociated test) or ELISA Ac+/p24+ or ELISA Ac+/p24- and WB-HIV-1 [0-5] band(s) or IB-HIV-1 [0-3] band(s) (confirmed by a positive HIV-1 RNA). Any result achieved in the previous 30 days of inclusion visit will be considered.
2. Aged 18 years or more, and less than 70 years, at the time of consent;
3. Participant who accepts the use of an effective method of contraception from the inclusion until the end of the follow-up in the trial (minimum 52 weeks). For men and trans women, his also applies to sperm donation;
4. For women or trans men: o negative plasmatic beta human chorionic gonadotropin (β-HCG) pregnancy test, o agree not to seek pregnancy including through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit,
5. Informed and written signed consent;
6. Participant with regular health insurance (AME is not considered as a regular health insurance);
7. Participant accepting additional constraints and: o willing to travel to one of the IMP administration centers (between D7ARV and D10ARV), o willing to interrupt ART,
8. Agreement to be vaccinated against COVID-19 before ATI, according to current recommendations.
9. Antiretroviral treatment not initiated prior to inclusion visit, with the exception of pre- or post-exposure prophylaxis ;
10. HIV-1 RNA greater than or equal to 10 000 copies/mL;

Exclusion criteria 18

1. Participation in any other clinical trial of an investigational agent or in any interventional or non-interventional study requiring additional blood sampling. Participation in an observational study without additional blood sampling is permitted;
2. Participants in whom condom use or PrEP use by the partner will be difficult or impossible;
3. Pregnant or breastfeeding woman or trans man
4. Participants under guardianship or curatorship
5. Any condition or infection, including HCV, HBV, SARS-CoV-2 or known M. tuberculosis active infection
6. History of ischemic heart disease (myocardial infarction, stable or unstable angina, stroke)
7. Current or past history of cancer, excluding squamous cell skin cancers
8. History or acute known inflammatory neurologic or ophthalmic affection (uveitis, choroiditis, optic neuropathy);
9. Any medical condition that contraindicates ART interruption
10. Concomitant or previous conditions that preclude injection of monoclonal antibodies
11. History of systemic corticosteroids, immunosuppressive and anti-cancer medications within the last 6 months
12. History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions
13. Individuals with any contraindication (including hypersensitivity reaction) to 3BNC117-LS and 10-1074-LS infusion;
14. Prothrombin < 50%
15. Creatinine clearance < 60mL/mn (CKD-EPI)
16. ASAT or ALAT or bilirubine (total et conjugated) ≥ 10 times the upper limit of normal
17. Patient with an isolated HIV-2 viral strain;
18. Planned absence that could affect participation in the trial (travel abroad, relocation, impending transfer...)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants with plasma HIV-1 RNA below 400 cp/mL 24 weeks following ATI, in the confirmed absence of ART. These participants will be considered as post-treatment controllers (PTC).

Secondary endpoints 11

1. Tolerability of intravenous infusions of bNAbs: number, grade, reason and time of clinical and biological adverse event (AE): o During ART, o During overall follow-up,
2. Proportion of participants resuming ART within the first 24 weeks of ATI, according to the reason for resuming;
3. Time to potential ART resumption for non-controllers;
4. Clinical and immulogical criteria, during ART (D0 to W52ARV (or W64ARV or W76ARV)), ATI (from D0ATI) and potential ART resumption (from D0Res to W24Res); o Proportion of participants with clinical symptoms, o Evolution of CD4, CD8 (levels and %) and CD4/CD8 ratio, o Evolution of inflammation markers levels
5. Virological criteria : o Plasma HIV-1 RNA and HIV-1 DNA level and cell-associated HIV RNA transcripts changes during ART (D0 to W52ARV (or W64ARV or W76ARV)), ATI (from D0ATI) and potential ART resumption (from D0Res to W24Res), o Proportion of participant with plasma HIV-1 RNA < 50 cp/mL at 12- and 24-weeks following ATI, o Cumulative plasma viremia during ATI,
6. Virological criteria : o In case of ART resumption:  Time from date of ATI begining to date of first VL ≥ 50 copies/mL,  Proportion of participant with plasma HIV-1 RNA < 50 copies/mL within 24 weeks of ART, o Evolution of total HIV-1 DNA and cell-associated HIV-1 RNA by US q-PCR and predictive value on post-ATI evolution, o Evolution of detection proportion and level of cell-associated HIV-1 RNA, oQualitative and quantitative changes in the persistent viral reservoir
7. Virological criteria :Evolution of total HIV-1 DNA and cell-associated HIV-1 RNA by US q-PCR and predictive value on post-ATI evolution, o Evolution of detection proportion and level of cell-associated HIV-1 RNA, o Qualitative and quantitative changes in the persistent viral reservoir,
8. Immunological criteria : o Changes in the magnitude and quality of HIV-specific T cell responses and humoral responses after infusions of bNAbs (W1ARV) and after ATI,
9. Pharmacological criteria : o Dosages of bNAbs performed after infusions (D0 to end of ATI period), o Dosages of ARV drugs performed during ATI (D0ATI to W24ATI)),
10. Criteria related to the risk of HIV-1 transmission: o Proportion of participants reporting to use condoms during sexual intercourse during follow-up, o Proportion of participants reporting to have proposed PrEP at their partners during ATI during follow-up,
11. Social sciences criteria : o Proportion of patients satisfied with their participation and the associated factors, o Impact of the participation in the trial on participant quality of life and quality of sexual life.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ANRS Maladies Infectieuses Emergentes

Sponsor organisation

ANRS Maladies Infectieuses Emergentes

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

ANRS Maladies Infectieuses Emergentes

Contact name

Josephine TINE

Public contact point

Organisation

ANRS Maladies Infectieuses Emergentes

Contact name

Josephine TINE

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications