Clinical Trials Register

Summary
EudraCT Number:	2021-001438-20
Sponsor's Protocol Code Number:	ASSTBS-FARM-INF_ITL-2021
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:	2021-08-02
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

2021-001438-20

A.3

Full title of the trial

Randomized controlled trial on daily Rifampicin for Four Months Compared with daily Rifampicin/Isoniazid for Three Months for the Treatment of Tuberculosis Infection among migrants: Completion Rate and Side Effects

Studio randomizzato controllato sul regime giornaliero con Rifampicina per la durata di quattro mesi rispetto al regime giornaliero con Rifampicina/Isoniazide per la durata di tre mesi per il trattamento dell’Infezione Tubercolare nella popolazione migrante: percentuale di completamento ed effetti collaterali

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

ITL-2021

A.4.1

Sponsor's protocol code number

ASSTBS-FARM-INF_ITL-2021

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	AZIENDA SOCIO SANITARIA TERRITORIALE DEGLI SPEDALI CIVILI DI BRESCIA
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	Programma Ricerca Finalizzata 2016
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	ASST Spedali Civili di Brescia
B.5.2	Functional name of contact point	progettazione ricerca e studi di fa
B.5.3	Address:
B.5.3.1	Street Address	p.le Spedali Civili 1
B.5.3.2	Town/ city	Brescia
B.5.3.3	Post code	25123
B.5.3.4	Country	Italy
B.5.4	Telephone number	0303998470
B.5.5	Fax number	030396125
B.5.6	E-mail	coordinamento.ricerca@asst-spedalicivili.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	RIFINAH - 300 MG + 150 MG COMPRESSE RIVESTITE 24 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI-AVENTIS S.P.A.
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	RIFAMPICINA/ISONIAZIDE
D.3.2	Product code	[RIFAMPICINA/ISONIAZIDE]
D.3.4	Pharmaceutical form	Gastro-resistant 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	RIFAMPICINA/ISONIAZIDE
D.3.9.2	Current sponsor code	rifampicina/isoniazide
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	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.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	Yes
D.2.1.1.1	Trade name	RIFADIN - 300 MG CAPSULE RIGIDE8 CAPSULE
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI-AVENTIS S.P.A.
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	rifampicina
D.3.2	Product code	[rifampicina]
D.3.4	Pharmaceutical form	Capsule, hard
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	RIFAMPICINA
D.3.9.2	Current sponsor code	RIFAMPICINA
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	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

Tuberculosis Infection

tubercolosi

E.1.1.1

Medical condition in easily understood language

Tuberculosis

tubercolosi

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10065048
E.1.2	Term	Latent tuberculosis
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10065048
E.1.2	Term	Latent tuberculosis
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 differences between the two study regimen (4R; 3HR) in terms of completion rate, adherence and side effects among migrant population.

Dimostrare il maggior tasso di completamento di un regime di trattamento giornaliero con Rifampicina per quattro mesi rispetto a un regime giornaliero con Rifampicina/Isoniazide per tre mesi.

E.2.2

Secondary objectives of the trial

A. To compare drug toxicity rates (any grade and grade 3, 4, or 5) associated with 4R and 3RH.
B. To compare the rates of drug discontinuation due to adverse drug reactions associated with 4R and 3RH.
C. To compare the rates of drug discontinuation for any reason associated with 4R and 3RH.

Confrontare la percentuale di eventi avversi di ogni grado e di grado 3, 4 e 5 associati con i due regimi di trattamento.
Confrontare le percentuali di sospensione del trattamento dovuta a reazioni avverse ai farmaci associate ai due regimi di trattamento.
Confrontare i tassi di sospensione del trattamento per qualsiasi ragione nei due bracci di trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Asylum seekers (AS) and refugees hosted in the SPRAR or CAS centers in the province of Brescia, Lombardia
Migrants residing in the province of Brescia, identified by the Transcultural and Migration Medicine Centre of ASST of Brescia
=5 years since arrival in Europe
=18 years old
Diagnosis of Tuberculosis Infection (TBI)
Provision of signed informed consent

Stranieri/e con status di richiedenti asilo e/o inseriti nel programma di accoglienza presso le strutture di ricezione della provincia di Brescia
Migranti identificati attraverso l’Ambulatorio Migranti dell’ASST Spedali Civili di Brescia
Ingresso in Europa entro i 5 anni precedenti
Uomini o donne non gravide/non in fase di allattamento, > 18 anni di età
Diagnosi di infezione tubercolare (TBI)
Capacità di fornire consenso

E.4

Principal exclusion criteria

Current confirmed culture-positive or clinical TB
Suspected TB
History of sensitivity/intolerance to any of the study drugs
<18 years old
Diagnosis of porphyria
Pregnant or breast-feeding females
Patients requiring medications that cannot be safely taken with any of the study drugs
Any medical condition deserving priority of treatment
Serum aminotransferase aspartate (AST, SGOT) > 5x upper limit of normal at the baseline evaluation
Clinical diagnosis of cirrhosis (jaundice, hematemesis, ascites or previous episodes of liver encephalopathy)
HIV positive
Previous treatment for TB or TBI

Diagnosi accertata o sospetta di TB attiva
Storia di allergia o intolleranza ad uno dei farmaci dello studio
Gravidanza o allattamento
Terapie concomitanti che interagiscono con i farmaci dello studio
Presenza di condizioni cliniche con priorità di intervento terapeutico
Età > 18 anni
Infezione da HIV
Valori sierici di transaminasi (AST) >5 volte i limiti di normalità
Cirrosi epatica
Diagnosi di porfiria
Pregresso trattamento per TB o TBI

E.5 End points

E.5.1

Primary end point(s)

Completion of the prescribed regimen, defined as taking at least 90% of the expected doses:
120 doses [at least 108 doses] of each drug within 120 days of treatment initiation with daily 4R (Arm 1);
90 doses [at least 81 doses] of each drug within 90 days of treatment initiation with daily 3HR (Arm 2);

Completamento del regime prescritto, definito come l'assunzione di almeno il 90% delle dosi previste:
¿ 120 dosi [almeno 108 dosi] di ciascun farmaco entro 120 giorni dall'inizio del trattamento con 4R giornaliere (braccio 1);
¿ 90 dosi [almeno 81 dosi] di ciascun farmaco entro 90 giorni dall'inizio del trattamento con 3HR giornaliere (Braccio 2);

E.5.1.1

Timepoint(s) of evaluation of this end point

90 120 days

90 -120 giorni

E.5.2

Secondary end point(s)

Mean proportion of cumulative number of pills taken for each group.; Permanent discontinuation of study drugs due to any adverse drug reactions.
Development of any grade and grade 3 or 4 drug-related toxicity.
Death due to any cause (grade 5 toxicity). Discontinuation of therapy for any reason.

Proporzione media del numero cumulativo di pillole prese per ogni gruppo.; Interruzione permanente dei farmaci in studio a causa di eventuali reazioni avverse al farmaco
Sviluppo di tossicità correlata al farmaco di qualsiasi grado e grado 3 o 4
cause di morte
interruzione della terapia

E.5.2.1

Timepoint(s) of evaluation of this end point

90-120 days; 90-120 days

90- 120 giorni; 90-120 giorni

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

E.6.5

Efficacy

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

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)

Yes

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

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

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

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:

244

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

264

F.4.2

For a multinational trial

F.4.2.1

In the EEA

264

F.4.2.2

In the whole clinical trial

264

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)

national health system

SSN

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

2021-05-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-06

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

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