Clinical Trials Register

Summary
EudraCT Number:	2019-002063-95
Sponsor's Protocol Code Number:	ASST-ITL-FARMA-INFE-2019
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-05-24
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

2019-002063-95

A.3

Full title of the trial

A Phase 3, Open, Randomized controlled trial on Completion Rate of daily Rifapentine/Isoniazid for One Month Compared with Daily Rifampicin/Isoniazid for Three Months for the Treatment of Latent Tuberculosis Infection among asylum seekers and refugees

Studio randomizzato, controllato, aperto di fase tre sul tasso di completamento di un regime giornaliero con Rifapentina/Isoniazide per un mese, comifampicina/Isparato a un regime giornaliero con Roniazide per tre mesi per il trattamento dell’infezione tubercolare latente tra richiedenti asilo.

A.3.1

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

Studio randomizzato, controllato, aperto di fase tre sul tasso di completamento di un regime giornaliero con Rifapentina/Isoniazide per un mese, comparato a un regime giornaliero con Rifampicina/Isoniazide per tre mesi per il trattamento dell’infezione tubercolare latente tra richiedenti asilo.

A.3.2

Name or abbreviated title of the trial where available

ITL2019

A.4.1

Sponsor's protocol code number

ASST-ITL-FARMA-INFE-2019

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	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	ASST SPEDALI CIVILI DI BRESCIA
B.5.2	Functional name of contact point	PROGETTAZIONE RICERCA CLINICA E STU
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	25124
B.5.3.4	Country	Italy
B.5.4	Telephone number	0303996851
B.5.5	Fax number	0303996125
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	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	00249750
D.3.9.2	Current sponsor code	rifampicina
D.3.9.3	Other descriptive name	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.IMP: 2
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	NICOZID 200mg compresse
D.2.1.1.2	Name of the Marketing Authorisation holder	PIAM FARMACEUTICI 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	isoniazide
D.3.2	Product code	[isoniazide]
D.3.4	Pharmaceutical form	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	00171300
D.3.9.2	Current sponsor code	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	200
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: 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	No
D.2.1.1.1	Trade name	Priftin
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	rifapentina
D.3.2	Product code	[M000473]
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	00622300
D.3.9.1	CAS number	61379-65-5
D.3.9.2	Current sponsor code	Rifapentine
D.3.9.3	Other descriptive name	Rifapentine
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	146
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

latent tuberculosis infection

infezione tubercolosi latente

E.1.1.1

Medical condition in easily understood language

latent tuberculosis

tubercolosi latente

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

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

The primary objective of this open-label randomized clinical trial is to compare completion rate, adherence and safety between the study regimen, 4 weeks rifapentine and isoniazid (1RPT/H) and the standard of care, 12 weeks isoniazid plus rifampicin (3HR).

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

E.2.2

Secondary objectives of the trial

The secondary objectives of this study include:
A. To evaluate adherence to treatment in the two groups measured by counting number of pills taken in each group.
B. To compare the rates of any grade and grade 3, 4, or 5 liver toxicity associated with 1RPT/H, and 3RH
C. To compare the rates of drug discontinuation due to adverse drug reactions associated with 1RPT/H and 3RH.
D. To compare the rates of drug discontinuation for any reason associated with 1RPT/H and 3RH.

Valutare l’aderenza al trattamento nei due bracci di studio, misurata contando il numero di compresse che vengono assunte in ogni gruppo di pazienti. ¿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

Man and woman
18 years old.HIV negative
Asylum seekers (AS) and refugees hosted in the SPRARS or CAS 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
Diagnosis of Latent Tuberculosis Infection (LTBI)
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 il Centro di Medicina Transculturale e delle Migrazioni dell’ASST Spedali Civili di Brescia
Uomini o donne
> 18 anni di età HIV negativo
Diagnosi di LTBI
Esclusione di TB attiva
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
Pregnant or breast-feeding females
Person with diagnosis of Porphyria
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)
Previous treatment for TB or LTBI

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

E.5 End points

E.5.1

Primary end point(s)

Completion of the prescribed regimen, defined as taking at least 90% of the doses:
• 28 doses [at least 25 doses] of each drug within 4 weeks of treatment initiation with daily 1RPT/H (Arm 1);
• 84 doses [at least 76 doses] within 12 weeks of treatment initiation with daily 3HR (Arm 2);

Completamento del regime terapeutico prescritto, definito come l’assunzione di almeno il 90% delle dosi:
- 28 dosi [almeno 25 dosi] di ciascun farmaco entro le 4 settimane dall’inizio del trattamento giornaliero 1RPT/H (Braccio 1);
- 84 dosi [almeno 76 dosi] di ciascun farmaco entro le 12 settimane dall’inizio del trattamento giornaliero 3HR (Braccio 2)

E.5.1.1

Timepoint(s) of evaluation of this end point

4 weeks
12 weeks

4 settimane
12 settimane

E.5.2

Secondary end point(s)

1. Mean proportion of cumulative number of pills taken for each group; tollerability

• Valutare l’aderenza al trattamento nei due bracci di studio, misurata contando il numero di compresse che vengono assunte in ogni gruppo di pazienti.; tollerabilità

E.5.2.1

Timepoint(s) of evaluation of this end point

4 weeks
12 weeks; 8 weeks
16 weeks

4 settimane
12 settimane; 8 settimane
16 settimane

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

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:

230

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

238

F.4.2

For a multinational trial

F.4.2.1

In the EEA

238

F.4.2.2

In the whole clinical trial

238

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)

at the end of the study the subjects will continue followup as regional plan for the management of the asylum seekers and refugees

al termine dello studio i soggetti continueranno eventuali controlli come da piano regionale per la gestione della popolazione richiedente asilo

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

2020-05-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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