Clinical Trials Register

Summary
EudraCT Number:	2020-003951-13
Sponsor's Protocol Code Number:	ANRS177DUETTO
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-02-18
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2020-003951-13

A.3

Full title of the trial

Randomized, open-label and multicentric trial evaluating the non-inferiority of antiretroviral dual therapy taken 4 consecutive days per week versus antiretroviral dual therapy 7/7 days per week in HIV-1 infected patients with controlled viral load under antiretroviral dual therapy ANRS 177 DUETTO.

Essai multicentrique, en ouvert, randomisé, évaluant la non-infériorité d’une bithérapie antirétrovirale prise 4 jours consécutifs sur 7 versus une bithérapie antirétrovirale prise en continu, chez des patients vivant avec le VIH en succès thérapeutique sous bithérapie.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Dual therapy in HIV patients in 4 days a week versus 7 days a week

Bithérapie chez des patients HIV en 4 jours sur 7 versus 7 jours sur 7

A.3.2

Name or abbreviated title of the trial where available

ANRS177DUETTO

A.4.1

Sponsor's protocol code number

ANRS177DUETTO

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	INSERM-ANRS
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ANRS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	INSERM-ANRS
B.5.2	Functional name of contact point	Cécile MOINS
B.5.3	Address:
B.5.3.1	Street Address	101 rue de Tolbiac
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75013
B.5.3.4	Country	France
B.5.4	Telephone number	33144236027
B.5.5	Fax number	33153946003
B.5.6	E-mail	cecile.moins@anrs.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	TIVICAY
D.2.1.1.2	Name of the Marketing Authorisation holder	ViiV Healthcare BV
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1051375-16-6
D.3.9.3	Other descriptive name	DOLUTEGRAVIR
D.3.9.4	EV Substance Code	SUB35122
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.1.1.1	Trade name	EPIVIR
D.2.1.1.2	Name of the Marketing Authorisation holder	ViiV Healthcare BV
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LAMIVUDINE
D.3.9.1	CAS number	134678-17-4
D.3.9.4	EV Substance Code	SUB08392MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	PREZISTA
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DARUNAVIR
D.3.9.1	CAS number	206361-99-1
D.3.9.4	EV Substance Code	SUB25394
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	800
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	EDURANT
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RILPIVIRINE
D.3.9.1	CAS number	500287-72-9
D.3.9.4	EV Substance Code	SUB31456
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NORVIR
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Deutschland GmbH & Co. KG
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RITONAVIR
D.3.9.1	CAS number	155213-67-5
D.3.9.4	EV Substance Code	SUB10342MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

HIV infection

Infection par le VIH

E.1.1.1

Medical condition in easily understood language

HIV infection

Infection par le VIH

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10020161
E.1.2	Term	HIV infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the non-inferiority at 48 weeks of dual therapy including Dolutegravir / Lamivudine or Dolutegravir / Rilpivirine or Darunavir/r/Lamivudine 4 consecutive days per week vs a dual therapy 7 days per week in HIV-controlled patients (Viral load < 50 cp/mL)

Evaluer la non-infériorité à 48 semaines de la stratégie de prise d’une bithérapie antirétrovirale comprenant du Dolutégravir / Lamivudine ou Dolutégravir / Rilpivirine ou Darunavir/r / Lamivudine prise à 4 jours consécutifs sur 7 versus une bithérapie en continu 7 jours sur 7, chez des patients vivant avec le VIH en succès virologique sous traitement antirétroviral par bithérapie (CV<50 copies/mL).

E.2.2

Secondary objectives of the trial

Therapeutic success at W48
Number of virological « blips » until W48
Subjects participating with any signal of viral replication when HIV RNA is under the limit of quantification between W0 and W48
Quantification of the viral reservoir in PBMC at W0 and W48 in relation with the virological response
Acquisition of drugs resistance mutations in case of virological failure detected
Frequency of minority resistant variants archived in DNA at W0 according to virological failure and acquisition of drugs resistance mutations
Clinical and biological tolerance
Evolution of CD4 - CD8 cell count, and CD4/CD8 ratio between W-4 and W48
Evolution of metabolic parameters between and weight W0 and W48
Evolution of inflammation and immune activation parameters at W0, W24 et W48
Residual plasmatic concentrations of the ARV at W0, W8, W24 and W48
HIV RNA viral load in semen at W0, W24 and W48
Treatment adherence at W0, W8, W24, W36 and W48
Quality of life at W-4, W0, W24 and W48

tx de succès thérapeutique à S48, de participants avec au moins un blip, une CV inférieure au seuil de détection et un signal détectable (PCR +)
Réservoir viral sur l’ADN total PBMC.
tx de participants avec des virus présentant des mutations de résistance, profil de résistance en cas d'échec virologique
Fréquence des variants résistants minoritaires archivés à S0 et au moment de l’échec virologique et de sélection de résistance
Tolérance clinique et biologique
L T CD4, CD8, rapport CD4/CD8 entre S-4 et S48
Evolution paramètres métaboliques du poids.
Paramètres d’activation et d’inflammation sériques
Dosage pharmacologique plasmatique des ARV à S0, S8, S24 et S48
La CV dans le compartiment spermatique réalisée à S0, S24 et S48
l’observance thérapeutique(auto-questionnaire) à S0, S8, S24, S36 et S48
qualité de vie (auto-questionnaire) à S-4, S0, S24 et S48

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

« immuno-virological » – 150 patients (75 in each arm)
Evolution of serum activation and inflammation parameters in a subgroup of patients (ancillary "immuno-virology" study: sCD14 / sCD163 / IP10 / CRP-us / Il-6 / D-Dimers / sTNFR1 / sTNFR2) at visits S0, S24 and S48.
« sperm »– 120 patients (60 in each arm)
Evolution of the viral load in the sperm compartment of S0, S24 and S48

« immuno-virologique » – 150 patients (75 patients dans chaque bras)
Niveau du réservoir viral déterminé sur l’ADN total dans les PBMC à J0 et S48 en relation avec la réponse virologique.- Evolution des paramètres sériques d’activation et d’inflammation dans un sous-groupe de patients (étude ancillaire « immuno-virologique » : sCD14 / sCD163 / IP10 / CRP-us / Il-6 / D-Dimères / sTNFR1 / sTNFR2) aux visites S0, S24 et S48

« sperme » – 120 patients (60 patients dans chaque bras)
Evolution de la charge virale dans le compartiment spermatique de S0, S24 et S48

E.3

Principal inclusion criteria

• HIV-1 infection, coinfection HIV-1/HIV-2 possible
• Age≥18 years old
• Current dual therapy unchanged for the last 6 months with Dolutegravir/ Lamivudine or Dolutegravir / Rilpivirine or Darunavir/r / Lamivudine
• If a genotype is available in the patient medical history; virus must be susceptible to all on going dual therapy. If no ARN genotype available, the patients can be included in the study
• Viral load (VL) < 50 c/mL in the past twelve months, with at least 3 VL measurements including screening; only one blip < 200 c/mL is authorized in the 6-12 previous months
• CD4 T cells > 250/mm3 at W-4
• Estimated glomerular filtration rate > 60 mL/min (CKD-EPI method)
• AST et ALT < 3N
• Haemoglobin > 10 g/dL
• Platelets > 100 000/mm3
• For women of childbearing age, negative pregnancy plasmatic test at W-4 and agree to use efficacy contraception during the study
• Commitment to use sexual prevention and protection methods throughout the trial.
• Social security system coverage (including State Medical Aid (AME), if EC approves it.
• Informed consent form signed

• Infection VIH-1 (co infection VIH-1/VIH-2 possible)
• Age ≥ 18 ans
• Traitement actuel non modifié depuis les 6 derniers mois (seul le changement de galénique est autorisé)
• Avoir une bithérapie antirétrovirale composée exclusivement :
1. Dolutégravir 50mg / Lamivudine 300mg – 1 prise par jour
2. Dolutégravir 50mg / Rilpivirine 25mg – 1 prise par jour
3. Darunavir/r 800mg/100mg / Lamivudine 300mg – 1 prise par jour
Les génériques sont acceptés dans le protocole.
• Si un génotype est disponible dans l'historique du patient ; le virus doit être sensible à toutes les molécules antirétrovirales des bithérapies proposées. Les patients sans génotypes à la pré-inclusion pourront être inclus en absence d’échec virologique antérieur
• Avoir une charge virale < 50cp/ml depuis au moins 12 mois. Un seul blip (< 200cp/ml) est autorisé sur la période 6-12 mois précédent la pré-inclusion
• Avoir au moins 3 mesures disponibles de CV < 50cp/ml sur les treize derniers mois (dont celle de la pré-inclusion)
• Lymphocytes CD4 > 250/mm3 à la pré-inclusion
• Clairance de la Créatinine > 50 mL/min (CKD-EPI)
• ASAT et ALAT < 3N
• Hémoglobine > 10 g/dL
• Plaquettes > 100 000/mm3
• Test de grossesse plasmatique négatif pour la femme à potentiel de grossesse et utilisation d’une contraception efficace tout au long de l’essai
• engagement à utiliser des moyens de prévention et de protection des rapports sexuels pendant toute la durée de l’essai
• Personne affiliée ou bénéficiaire d’un régime de sécurité sociale (article L1121-11 du Code de la Santé Publique), de l'Aide Médicale d'Etat (AME) sous réserve de l'accord du CPP.
• Consentement libre, éclairé, écrit, signé par la personne et l'investigateur au plus tard le jour de l'inclusion et avant tout examen réalisé dans le cadre de l'étude (article L1122-1-1 du Code de la Santé Publique)

E.4

Principal exclusion criteria

• Infection by HIV-2
• Chronic and active Viral B Hepatitis with positive antigen HBs
• Chronic and active Viral C Hepatitis with treatment expected in the next 48 weeks
• Concomitant treatment using interferon, interleukins, any other immune-therapy or chemotherapy, antivitamin K+ with co-treatment by booster
• Concomitant prophylactic or curative treatment for an opportunistic infection
• All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with study protocol compliance, observance and/or study treatment tolerance
• Pregnant or breast feeding women
• Subjects under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship

• Infection par le VIH-2
• Hépatite virale B chronique active avec antigène Hbs positif
• Hépatite virale C chronique active nécessitant une mise sous traitement spécifique au cours des 48 semaines à venir.
• Traitement par anti-vitamine K (pour les patients sous ARV boostés), interféron, interleukine, ou toute autre immunothérapie, chimiothérapie en cours
• Infection opportuniste évolutive, ou traitement d’attaque pour infection opportuniste
• Toute condition (alcool, drogue, atteintes neurologiques, neuropsychiatriques…) susceptible de compromettre la tolérance du traitement et/ou l’observance du patient au traitement et son adhésion au protocole selon le jugement de l’investigateur
• Femme enceinte ou allaitante ou refus de contraception
• Incapacité majeure, sauvegarde de justice, tutelle ou curatelle

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with virological failure at W48.
The virological failure is defined by 2 successive viral loads >50 c/mL at 2 to 4 weeks apart or a viral load > 50 c/ml with a definitive stop of the study follow-up or the study strategy

Pourcentage de participants en échec virologique à la semaine 48.
L’échec virologique est défini par la survenue de 2 mesures de charge virale successives >50 copies/mL ou une mesure >50 copies/mL suivie de l’arrêt définitif de la stratégie ou du suivi dans l’essai au cours des 48 semaines de suivi.

E.5.1.1

Timepoint(s) of evaluation of this end point

At week 48

Semaine 48

E.5.2

Secondary end point(s)

• Proportion of participants with therapeutic success until W48
• Percentage of participants with at least one episode of "blip" (viral load >50 copies/mL followed by a control value ≤ 50 cp/mL) between W0 and W48
• Percentage of participants with a viral load signal detected between W0 and W48
• Evolution of ultrasensitive viral load and total DNA in the PBMC at W0 and W48 (immuno-virological sub-study)
• Proportion of participants with acquisition of drugs resistance mutations in case of virological failure detected by Sanger and by NGS
• Description of selected mutations at the virological failure
• Frequency of minority resistant variants archived in DNA at W0 and their impact on virological failure (2 consecutive VL> 50 copies / mL) and on the acquisition of drugs resistance mutations
• Frequency of grade 3 or more adverse events, adverse effects, drug-modifying adverse events, drug-related adverse events and serious adverse events (SAE)
• Evolution of T CD4 and CD8 cells count, and CD4/CD8 ratio from W-4 to W48
• Evolution of fasting metabolic parameters (total cholesterol total, LDL-C, HDL-C, Triglycerides and glycemia) until W0 and W48
• Evolution of weight between W0 and W48
• Evolution of inflammation serum parameters - immuno-virological sub-study- (sCD14, sCD163, IP-10, CRPus, IL-6, D-dimers, sTNFR1, sTNFR2) from W0 to W24 and W48 (150 participants forecast)
• Evolution of semen viral load at W0, W24 and W48 (120 participants forecast).
• Description and comparison of plasmatic concentrations of antiretroviral agents between the 2 groups at ON and OFF period
• Evaluation of the adherence by self-reported questionnaire at W0, W8, W24, W36 and W48
• Evolution of the quality of life by self-reported questionnaire between W-4 and W48

• Pourcentage de participants en succès thérapeutique à S48 (absence d’échec virologique et d’arrêt définitif de la stratégie ou du suivi dans l’essai)
• Pourcentage de participants présentant au moins un "blip" (charge virale supérieure à 50 copies/mL avec un contrôle consécutif inférieur ou égal à 50 copies/mL) entre S0 et S48
• Pourcentage de participants présentant une charge virale avec un signal détectable (PCR+) lorsque celle-ci est inférieure au seuil de détection de la technique entre S0 et S48.
• Détermination du niveau du réservoir viral par la quantification de l’ADN total dans les PBMC à J0 et S48 en relation avec la réponse virologique (étude ancillaire immuno-virologique)
• Pourcentage de participants avec des virus présentant des mutations de résistance au traitement en cours en cas d’échec virologique (Séquençage classique par Sanger)
• Description des mutations de résistance sélectionnées au moment de l’échec virologique.
• La proportion de variants résistants minoritaires archivés dans l’ADN à S0 et son impact sur le risque d’échec virologique avec la sélection de mutation de résistance
• Incidence des événements indésirables clinique et biologique de grade 3 ou plus, incidence des effets indésirables, et incidence des arrêts de la stratégie sur les 48 semaines de suivi.
• Evolution des lymphocytes T CD4 et CD8, et du rapport CD4/CD8 de S-4 à S48
• Evolution des paramètres métaboliques (Cholestérol total, LDL-c, HDL-c, Triglycérides et glycémie à jeun) de S0 à S48
• Evolution du poids entre S0 et S48
• Evolution des paramètres sériques d’activation et d’inflammation dans un sous-groupe de patients (étude ancillaire « immuno-virologique » : sCD14 / sCD163 / IP10 / CRP-us / Il-6 / D-Dimères / sTNFR1 / sTNFR2) aux visites S0, S24 et S48
• Description des concentrations plasmatiques des molécules antirétrovirales et comparaison entre les groupes des concentrations mesurées en ON et les concentrations mesurées en OFF
• Evolution de la charge virale dans le compartiment spermatique de S0, S24 et S48 (étude ancillaire « sperme » chez 120 participants).
• Evaluation de l’observance des participants par auto-questionnaire à S0, S8, S24, S36 et S48
• Evolution de la qualité de vie des participants évalués par auto-questionnaire de S-4 à S48

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluation throughout the trial

Evaluation tout au long de l'essai

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

48 weeks after the last patient's last visit, in order to complete centralized biological analyses, monitoring, statistical analyses and publication of results.

48 semaines après la dernière visite du dernier patient, afin de terminer les analyses biologiques centralisées, le monitoring, les analyses statistiques et la publication des résultats.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

420

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

440

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

If the effectiveness of the innovative strategy on 4 consecutive days out of 7 is demonstrated by the trial, the long-term continuation of the intermittent strategy (4 consecutive days out of 7) will be supported for all participants.

Si l’efficacité de la stratégie novatrice à 4 jours consécutifs sur 7 est démontrée par l’essai, la poursuite au long cours de la stratégie intermittente (4 jours consécutifs sur 7) sera confortée pour l’ensemble des participants.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-03-29

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials