Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
32
Countries
1
Sites
9
Patients living with HIV-1 who are virologically controlled and carry an M184V/I mutation in a previous genotype
Efficacy of the Doravirine / TDF / Lamivudine combination for 24 weeks on virological efficacy in the event of a history of M184V/I mutation not present on the current proviral DNA.
Key facts
- Sponsor
- Centre Hospitalier Universitaire De Caen Normandie
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Virus Diseases [C02]
- Trial duration
- 8 Feb 2024 → ongoing
- Decision date (initial)
- 2023-11-15
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- CHU CAEN Normandie
External identifiers
- EU CT number
- 2023-505845-17-00
- ClinicalTrials.gov
- NCT06034938
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
Efficacy of the Doravirine / TDF / Lamivudine combination for 24 weeks on virological efficacy in the event of a history of M184V/I mutation not present on the current proviral DNA.
Secondary objectives 1
- Effectiveness at 48 weeks; Immunological effectiveness; To describe changes after switching to DOR/TDF/3TC in terms of proviral HIV DNA, weight, lipids, renal parameter profile and quality of life
Conditions and MedDRA coding
Patients living with HIV-1 who are virologically controlled and carry an M184V/I mutation in a previous genotype
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10020160 | HIV disease | 10021881 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Adult patient living with HIV-1
- Receiving stable antiretroviral treatment for at least 3 months
- HIV RNA VL<50cp/mL for at least 6 months
- Presence of the M184V/I mutation in at least one previous genotype performed on plasma HIV-RNA (at least 6 months undetectable), but absent from the genotype on current standard proviral DNA (Sanger technique)
- Signed informed consent
- At inclusion, the patient must present complete sensitivity to doravirine and tenofovir according to the genotype of the proviral DNA centralized in Saint-Louis
Exclusion criteria 11
- M184V/I mutation present at inclusion on the standard proviral DNA genotype (Sanger technique)
- Contraindication to the use of DOR/TDF/3TC
- Hypersensitivity to doravirine, tenofovir, lamivudine or one of the excipients (notably lactose)
- Current or recent treatments with a strong CYP3A4 inducer
- Feeding with milk
- Pregnancy
- Patient already under DOR
- Patients under guardianship or curatorship
- Resistance to DOR on a previous genotype carried out on plasma HIV-RNA OR on standard proviral DNA
- Resistance to TDF on a previous genotype carried out on plasma HIV-RNA OR on standard proviral DNA
- Patient who has received injectable antiretroviral treatment for less than 12 months
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Concerning the main analysis, the proportion of patients with an undetectable viral load at 24 weeks will be carried out per-protocol, that is to say that subjects who interrupt the experimental treatment without having reached a classifying event for the main criterion judgment or lost to follow-up will not be considered failures. A sensitivity analysis will be conducted, according to the FDA snapshot algorithm, on an intention-to-treat-exposed (ITT-e) basis.
Secondary endpoints 7
- Proportion of patients with an undetectable viral load (<50 copies/ml) at 48 weeks, according to the FDA's intention-to-treat-exposed (ITT-e) snapshot algorithm. The intention-to-treat exposed population includes all patients who received at least one dose of DOR/3TC/TDF.
- volution of the NGS genotype on proviral DNA between baseline, S24 and S48
- Delta CD4 between BL, S24 and S48
- Delta weight between BL, S24 and S48
- Delta LDL, HDL, Triglycerides and total cholesterol between BL, W24 and W48
- Delta QoL SF36 between BL, S24 and S48
- HIVTSQc overall score at S12
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Delstrigo 100 mg/300 mg/245 mg film-coated tablets
PRD6778264 · Product
- Active substance
- Lamivudine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- J05AR24 — -
- Marketing authorisation
- EU/1/18/1333/001
- MA holder
- MERCK SHARP & DOHME B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire De Caen Normandie
- Sponsor organisation
- Centre Hospitalier Universitaire De Caen Normandie
- Address
- Avenue De La Cote De Nacre, Cs 30001 Cs 30001
- City
- Caen Cedex 9
- Postcode
- 14033
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Caen Normandie
- Contact name
- Investigateur Coordinateur
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Caen Normandie
- Contact name
- Investigateur Coordinateur
Locations
1 EU/EEA country · 9 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 32 | 9 |
| Rest of world | — | 0 | — |
Investigational sites
Assistance Publique Hopitaux De Paris
Infectiologie, 43 Boulevard De L Hopital, 75013, Paris
Centre Hospitalier Universitaire d'Orléans
Infectiologie, La source, 45100, ORLEANS
Centre Hospitalier Universitaire De Montpellier
Infectiologie, 191 Avenue Du Doyen Gaston Giraud, 34295, Montpellier Cedex 5
Assistance Publique Hopitaux De Paris
Infectiologie, 2 Rue Ambroise Pare, 75475, Paris Cedex 10
CHU De Rouen
Infectiologie, 1 Rue De Germont, Bp 96031, Rouen Cedex
Centre Hospitalier De Tourcoing
Infectiologie, 155 Rue Du President Coty, Bp 40619, Tourcoing Cedex
Centre Hospitalier Universitaire De Caen Normandie
Infectiologie, Avenue De La Cote De Nacre, Cs 30001, Caen Cedex 9
Hopital Saint Louis
Infectiologie, 1 Avenue Claude Vellefaux, 75010, Paris
Assistance Publique Hopitaux De Paris
Infectiologie, 184 Rue Du Faubourg Saint Antoine, 75012, Paris
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-02-08 | 2024-02-08 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Urgent safety measures 1 · Art. 54 CTR
Urgent safety measure US-64095
- Event date
- 2024-12-18
- Submission date
- 2024-12-19
- In response to
- OTHER
- Member states affected
- France
- Event description
- Nous vous informons qu’une nouvelle version du Résumé des Caractéristiques du Produit (RCP) de la spécialité DELSTRIGO®, utilisée comme médicament expérimental de l’étude DRIVE OFF ROAD, est disponible depuis septembre 2024. Cette nouvelle version intègre dorénavant en section 4.4 (Mises en garde spéciales et précautions d’emploi) une nouvelle information de sécurité que nous avons considérée comme importante, à savoir le risque de survenue de réactions cutanées sévères (notamment syndrome de Stevens-Johnson et syndrome de Lyell) sous doravirine : ‘’ Des réactions cutanées sévères (SCAR) dont le syndrome de Stevens-Johnson (SSJ)/nécrolyse épidermique toxique (NET), ont été signalées après la commercialisation de traitements contenant de la doravirine (voir rubrique 4.8). Au moment de la prescription les patients doivent être informés des signes et symptômes et faire l’objet d’une surveillance étroite des réactions cutanées. En cas d’apparition de signes et symptômes évocateurs de ces réactions, les traitements contenant de la doravirine doivent être immédiatement arrêtés et un traitement alternatif doit être envisagé (le cas échéant). L'état clinique doit être étroitement surveillé, et un traitement approprié doit être instauré. Si le patient a développé une réaction sévère telle qu'une NET, lors de l'utilisation de traitements contenant de la doravirine, un traitement contenant de la doravirine ne doit à aucun moment être repris chez ce patient. ’’
- Measures taken
- Cette mise à jour du RCP, considérée comme un fait nouveau de sécurité d’après la réglementation en vigueur, a conduit le promoteur à mettre en place les mesures suivantes :
- Modification substantielle du protocole (MS n° 2 à venir)
- Mise à jour de la note d’information à destination des patients
- Communication de cette information aux autorités compétentes
Par conséquent, dès à présent, nous vous recommandons d’appliquer les mesures suivantes :
Pour tous les patients, actuels et futurs :
o S’assurer que le patient n’a pas d’antécédent de survenue de réaction cutanée sévère sous doravirine,
o Les informer des signes et symptômes pouvant être évocateurs de ces réactions cutanées sévères, avec arrêt du traitement et appel immédiat de l’investigateur le cas échéant,
o Les informer qu’ils feront l’objet d’une surveillance dermatologique par l’investigateur à l’occasion des visites de suivi.
Pour tous les patients actuellement inclus et en cours de traitement :
o Prise de connaissance de ce nouveau risque et de sa surveillance, puis signature de la nouvelle version de la note d’information à destination des patients.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 18 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | 2023-505845-17-00_COMPARATIF_MS1_DOR | 1 |
| Protocol (for publication) | 2023-505845-17-00_PROTOCOLE_DOR | 06 |
| Protocol (for publication) | 2023-505845-17-00_PROTOCOLE_signe_DOR | 4 |
| Protocol (for publication) | 2023-505845-17-00_PROTOCOLESIG_DOR | 06 |
| Recruitment arrangements (for publication) | 2023-505845-17-00_INFORMATION_RECRUTEMENT_DOR | 1 |
| Recruitment arrangements (for publication) | 2023-505845-17-00_INFORMATION_RECRUTEMENT_DOR | 1 |
| Subject information and informed consent form (for publication) | 2023-505845-17-00_CarnetPatientN1_DOR | 1 |
| Subject information and informed consent form (for publication) | 2023-505845-17-00_CarnetPatientN2_DOR | 1 |
| Subject information and informed consent form (for publication) | 2023-505845-17-00_CarnetPatientN3_DOR | 1 |
| Subject information and informed consent form (for publication) | 2023-505845-17-00_CarnetPatientN4_DOR | 1 |
| Subject information and informed consent form (for publication) | 2023-505845-17-00_CARTE_PATIENT_DOR | 3 |
| Subject information and informed consent form (for publication) | 2023-505845-17-00_FC_DOR | 2 |
| Subject information and informed consent form (for publication) | 2023-505845-17-00_NI_clean_DOR | 4 |
| Subject information and informed consent form (for publication) | 2023-505845-17-00_NI_DOR | 6 |
| Summary of Product Characteristics (SmPC) (for publication) | 2023-505845-17-00_RCP_DELSTRIGO_DOR | 1 |
| Synopsis of the protocol (for publication) | 2023-505845-17-00_COMPARATIF_RESUME_MS1_DOR | 1 |
| Synopsis of the protocol (for publication) | 2023-505845-17-00_RESUME_DOR | 6 |
| Synopsis of the protocol (for publication) | 2023-505845-17-00_RESUMESIMPLE_DOR | 2 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-08-25 | France | Acceptable 2023-11-15
|
2023-11-15 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-05 | France | Acceptable 2024-09-12
|
2024-10-04 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-01-02 | France | Acceptable with conditions 2025-03-10
|
2025-03-14 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-08-26 | France | Acceptable 2025-10-22
|
2025-11-05 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2026-01-22 | France | Acceptable 2026-02-13
|
2026-02-27 |