Clinical Trials Register

Summary
EudraCT Number:	2020-006102-23
Sponsor's Protocol Code Number:	ImmuneRaRe_RF-2019-12369708
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-07
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-006102-23

A.3

Full title of the trial

Study of a novel combination of immunovirologic and genetic parameters in early-treated HIV-1 patients undergone to antiretroviral therapy interruption (ATI) aimed at defining an algorithm predictive of post-treatment control (PCT)

Studio di una nuova combinazione di parametri immunovirologici e genetici in pazienti affetti da HIV 1 trattati precocemente e sottoposti ad interruzione della terapia antiretrovirale (ATI) per definire un algoritmo predittivo del controllo post-trattamento (PCT)

A.3.1

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

Study of the genetic, viral and immune response characteristics of a group of patients infected with the AIDS virus treated early and then subjected to suspension of antiretroviral therapy to define biological markers predicting the control of virus replication after pharmacological treatment

Studio delle caratteristiche genetiche, virali e della risposta immune di un gruppo di pazienti infettati dal virus dell'AIDS trattati precocemente e poi sottoposti a sospensione della terapia antiretrovirale per definire i marcatori biologici predittori del controllo della replicazione del virus dopo trattamento farmacologico

A.3.2

Name or abbreviated title of the trial where available

ImmuneRaRe_RF-2019-12369708

A.4.1

Sponsor's protocol code number

ImmuneRaRe_RF-2019-12369708

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	OSPEDALE SAN RAFFAELE
B.1.3.4	Country	Italy
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	Ministero della Salute
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ospedale San Raffaele
B.5.2	Functional name of contact point	Ospedale San Raffaele
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina 60
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0226433473
B.5.5	Fax number	02264337909
B.5.6	E-mail	castagna.antonella1@hsr.it

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	JULUCA
D.2.1.1.2	Name of the Marketing Authorisation holder	VIIV HEALTHCARE BV AIC: 046638019
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.1	Product name	ART
D.3.2	Product code	[ART]
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	DOLUTEGRAVIR
D.3.9.2	Current sponsor code	ART
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RILPIVIRINA
D.3.9.2	Current sponsor code	ART
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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-1 positive subjects treated with effective antiretroviral therapy during the acute phase of HIV-1 infection

Soggetti sieropositivi a HIV-1 trattati con terapia antiretrovirale efficace durante la fase acuta dell'infezione da HIV-1

E.1.1.1

Medical condition in easily understood language

People infected with the AIDS virus who have been successfully treated with antiretroviral drugs during the early stage of infection

Soggeti infettati con il virus dell'AIDS che sono stati trattati con successo coni farmaci antiretrovirali durante la fase precoce dell'infezione

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10068341
E.1.2	Term	HIV-1 infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Step 1: Investigate a set of immune-genetic and viroimmunologic biomarkers that might be useful to individuate PTC

Step 2: Validate the Predictive Algorithms of PTC

Step 1: Indagare una serie di biomarcatori immunogenetici e viro-immunologici che potrebbero essere utili per individuare i pazienti capaci di controllo viremico post-trattamento (PTC)

Step 2: Convalidare gli algoritmi predittivi della PTC

E.2.2

Secondary objectives of the trial

Step1: Validation of the immune-genetics platform for the genotyping of KIRs/TRIM22/SNPs regulating HLA-C expression and HLA A-B-C supratyping in a clinical setting

Step 2: Evaluate the time of HIV-1 plasma load relapse and/or loss of a stable CD4 T-cell count = 350 cells/mm3 occurring in patients subjected to MAP

Step 1: Validazione della piattaforma di immunogenetica per la genotipizzazione di KIRs/TRIM22/SNPs che regolano l'espressione HLA-C e la sovratipizzazione HLA A-B-C nella gestione dei pazienti nella pratica clinica

Step 2: Valutare il tempo di rimbalzo del carico plasmatico di HIV-1 e/o la perdita di una conta stabile di cellule T CD4 = 350 cellule/mm3 che si verifica nei pazienti sottoposti alla pausa monitorata di terapia (MAP)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male or female, aged 18-60 years
Confirmed HIV-1 seropositive documented
ART commenced during primary HIV infection, as defined by Fiebig stage
Plasma HIV-RNA < 50 copies/ml for at least 24 months
CD4+ T cell count > 350 cells/mm3 at the last routine follow-up visit
No new AIDS-defining diagnosis or progression of HIV-related disease
Able to adhere to an effective ART regimen for the duration of the study
Willing and able to give written informed consent for participation in the study

Maschio o femmina, di età compresa tra i 18 e i 60 anni
Documentazione di sieropositività confermata di HIV-1
ART iniziata durante l'infezione primaria da HIV, come definito dalla stadiazione di Fiebig
Plasma HIV-RNA <50 copie/ml per almeno 24 mesi
Conteggio delle cellule CD4+ T > 350 cellule/mm3 all'ultima visita di controllo di routine
Nessuna nuova diagnosi che definisca l'AIDS o la progressione della malattia legata all'HIV
In grado di aderire ad un efficace regime ART per tutta la durata dello studio
Disponibilità e capacità di dare il consenso informato scritto per la partecipazione allo studio

E.4

Principal exclusion criteria

Confirmed HIV-2 seropositive
Women who are pregnant
History of systemic cancer, such as Kaposi’s sarcoma and lymphoma, or other virus-associated malignancies and/or history of AIDS-defining illness according to Centers for Disease Control and Prevention criteria
Active or chronic hepatitis B virus infection, with detectable hepatitis B surface antigen, hepatitis B virus DNA, or both active and chronic hepatitis C virus infection, with detectable virus RNA, and syphilis

Only Step 2
Naso-pharyngeal swab positive for SARS-CoV-2

Sieropositivo confermato HIV-2
Donne gravide
Storia di tumori sistemici, come il sarcoma di Kaposi, il linfoma o altri tumori maligni associati al virus e/o
storia di malattie che definiscono l'AIDS secondo i criteri del CDC.
Infezione attiva o cronica da virus dell'epatite B, con antigene di superficie rilevabile dell'epatite B, DNA del virus dell'epatite B o infezione sia attiva che cronica da virus dell'epatite C, con RNA del virus rilevabile, e sifilide

Solo Step 2
Tampone naso-faringeo positivo per SARS-CoV-2

E.5 End points

E.5.1

Primary end point(s)

Step 1: To complete the immune-virologic and immune-genetic profiling of volunteers enrolled in the study and perform all the statistical analysis within the time frame proposed (21 months) before the beginning of the MAP cohort recruitment

Step 2: Proportion of participants who controlled viremia counts (<50%) and maintained a stable CD4 T-cell count = 350 cells/µl for all the follow-up (6 months) (no CD4 significant drop)

Step 1: Completare il profilo immuno-virologico e immuno-genetico dei volontari arruolati nello studio ed eseguire tutte le analisi statistiche entro il periodo di tempo proposto (21 mesi) prima dell'inizio del reclutamento della coorte MAP

Step 2: Percentuale dei partecipanti che hanno controllato il carico viremico (<50%) e mantenuto un conteggio stabile delle cellule T CD4 = 350 cellule/mm3 per tutto il follow-up (6 mesi) (nessun calo significativo di CD4)

E.5.1.1

Timepoint(s) of evaluation of this end point

STEP 1 - 21 months

STEP 2 - 6 months

STEP 1 - 21 mesi

STEP 2 - 6 mesi

E.5.2

Secondary end point(s)

Step 2: Proportion of participants who controlled viremia without a significant drop of CD4 T-cell counts (<50%) for = 3 months but <6 months; Step 2: Proportion of individuals in whom ART is reinitiated due to viral rebound (pVL =100000 copies/ml or 2 consecutive pVL =10000 copies/ml 7 days apart), >50% drop in CD4 cell counts, <350 cells/mm3 and/or symptomatic acute retroviral syndrome; Step 2: Proportion of participants who maintained a CD4 T cell count =350 cells but experienced viral rebound; Step 2: Time to viral rebound during MAP; Step 1: To complete the immune-genetics platform set-up and validation on reference samples

Step 2: Percentuale dei partecipanti che hanno controllato la viremia senza un calo significativo della conta delle cellule T CD4 (<50%) per =3 mesi ma <6 mesi; Step 2: Percentuale di individui in cui la terapia antiretrovirale (ART) viene reintrodotta a causa del rimbalzo virale (carico virale plasmatico = pVL =100000 copie/ml o 2 pVL consecutivi =10000 copie/ml a 7 giorni di distanza l'uno dall'altro), >50% di calo della conta delle cellule CD4, <350 cellule/mm3 e/o sindrome retrovirale acuta sintomatica; Step 2: Percentuale dei partecipanti che hanno mantenuto un numero di cellule T CD4 =350 ma hanno sperimentato un rimbalzo virale; Step 2: Tempo al rimbalzo virale durante la MAP; Step 1: completamento e validazione con campioni di riferimento della piattaforma delle analisi immunogenetiche

E.5.2.1

Timepoint(s) of evaluation of this end point

10 months; 6 months; 6 months; 10 months; 1 years

10 mesi; 6 mesi; 6 mesi; 10 mesi; 1 anno

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

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

Yes

E.8.2.3.1

Comparator description

Non esiste un comparatore

There is no comparator

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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

LVLS

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

100

F.1.3

Elderly (>=65 years)

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

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)

will be followed for 6 months with more stringent monitoring than normal clinical practice (every three months) and then as per clinical practice

verranno seguiti per 6 mesi con un monitoraggio più stringente rispetto alla normale pratica clinica (ogni tre mesi) e poi come da pratica clinica

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

2021-04-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-10-13

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

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