ICH GCP - EU Clinical trials Registry - 2019-003370-35 (IT)

Stránka klinických studií Nct

Summary
EudraCT Number:	2019-003370-35
Sponsor's Protocol Code Number:	MCT8-2019-2
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:	2021-05-24
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

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-003370-35

A.3

Full title of the trial

Tiratricol treatment of children with Monocarboxylate Transporter 8 deficiency: Triac Trial II

Trattamento con Tiratricol nei bambini con deficit del trasportatore 8 dei monocarbossilati: Triac Trial II

A.3.1

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

Tiratricol treatment of children with Monocarboxylate Transporter 8 deficiency: Triac Trial II

Trattamento con Tiratricol nei bambini con deficit del trasportatore 8 dei monocarbossilati: Triac Trial II

A.3.2

Name or abbreviated title of the trial where available

Triac Trial II

A.4.1

Sponsor's protocol code number

MCT8-2019-2

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02396459

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	Rare Thyroid Therapeutics International
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Eurostars
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Rare Thyroid Therapeutics International AB
B.5.2	Functional name of contact point	Medical Director
B.5.3	Address:
B.5.3.1	Street Address	Teatergatan 3
B.5.3.2	Town/ city	Stoccolma
B.5.3.3	Post code	11148
B.5.3.4	Country	Sweden
B.5.6	E-mail	medical@rarethyroid.com

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/17/1945
D.3 Description of the IMP
D.3.1	Product name	emcitate
D.3.2	Product code	[emcitate]
D.3.4	Pharmaceutical form	Lozenge
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	Tiratricol
D.3.9.1	CAS number	51-24-1
D.3.9.2	Current sponsor code	Tiratricol
D.3.9.3	Other descriptive name	Tiratricol
D.3.9.4	EV Substance Code	SUB11116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(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	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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/17/1945
D.3 Description of the IMP
D.3.1	Product name	Emcitate
D.3.2	Product code	[Emcitate]
D.3.4	Pharmaceutical form	Lozenge
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	Tiratricol
D.3.9.1	CAS number	21-24-1
D.3.9.2	Current sponsor code	Tiratricol
D.3.9.3	Other descriptive name	Tiratricol
D.3.9.4	EV Substance Code	SUB11116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	350
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

Monocarboxylate Transporter 8 (MCT8) deficiency

deficit del trasportatore 8 dei monocarbossilati (MCT8)

E.1.1.1

Medical condition in easily understood language

MCT 8 deficiency or AHDS (Allan-Herndon-Dudley syndrome)

deficit MCT8 o sindrome di Allan-Herndon-Dudley

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

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	10078564
E.1.2	Term	Thyroid stimulating hormone deficiency
E.1.2	System Organ Class	10014698 - Endocrine disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effects of tiratricol treatment on neurodevelopment in young MCT8 deficiency patients as measured by the Gross Motor Function Measure 88 (GMFM-88).

Valutare gli effetti di tiratricol sul neurosviluppo in pazienti in età evolutiva con deficit di MCT8, misurata in base alla scala Gross Motor Function Measure (GMFM-88).

E.2.2

Secondary objectives of the trial

1) To evaluate the effect of tiratricol treatment on specific Motor Development milestones by individual item scores in the Gross Motor Function Measure test.

2) To evaluate the effect of tiratricol treatment on neurodevelopment in young MCT8 deficient patients as measured by the Bayley Scales of Infant Development (BSID-III).

3) Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features (serum T3 concentrations, tissue specific markers of thyroid hormone action).

1. Valutare l'effetto del trattamento con tiratricol su specifici traguardi di sviluppo motorio in base ai punteggi individuali nel test Gross Motor Function Measure
2. Valutare l'effetto del trattamento con tiratricol sul neurosviluppo in base alle Bayley Scales of Infant Development (BSID-III)
3. Valutare l'effetto di tiratricol sulle caratteristiche tireotossiche cliniche e biochimiche (concentrazioni sieriche di T3, marcatori tessutali specifici dell'azione dell'ormone tiroideo).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Signed and dated informed consent form from the parents or legal guardian.
2.Parents stated willingness to comply with all study procedures and availability for the duration of the study.
3.The participant should be aged between 0 and 30 months on the day of inclusion.
4.The participant should have a pathogenic mutation in the MCT8 gene.

1. Modulo di consenso informato firmato e datato dai genitori o dal tutore legale.
2. I genitori hanno volontariamente dichiarato di rispettare tutte le procedure di studio e di essere disponibili per tutta la durata dello studio.
3. Il partecipante deve avere un'età compresa tra 0 e 30 mesi, al giorno dell'inclusione.
4. Il partecipante dovrebbe presentare una mutazione patogena nel gene MCT8.

E.4

Principal exclusion criteria

1. Previous treatment with tiratricol.
2. Previous treatment with a combination of Propylthiouracil (PTU) and Levothyroxine (LT4).
3. Previous treatment with LT4 for a longer period than three months.
4. Treatment with LT4 within three months of baseline visit.
5. Major illness or recent major surgery (within four weeks of baseline visit 1) unrelated to MCT8 deficiency.
6. Known allergic reactions to components of the IMP.
7. Treatment with another investigational drug or participation in other interventional trial within three months prior to baseline visit 1.
8. Patients that have any contra-indication for tiratricol treatment as stated in the Investigators Brochure.

1. Trattamento precedente con tiratricol.
2. Trattamento precedente con una combinazione di propiltiouracile (PTU) e levotiroxina (LT4).
3. Trattamento precedente con LT4 per un periodo più lungo di tre mesi.
4. Trattamento con LT4 entro tre mesi dalla visita basale.
5. Malattia grave o recente intervento chirurgico maggiore (entro quattro settimane dalla visita basale 1) non correlato al deficit di MCT8.
6. Reazioni allergiche note ai componenti dell'IMP.
7. Trattamento con un altro farmaco sperimentale o partecipazione ad altri studi interventistici entro tre mesi prima della visita basale 1.
8. Pazienti che hanno controindicazioni per il trattamento con tiratricol come indicato nell'Investigators brochure

E.5 End points

E.5.1

Primary end point(s)

GMFM-88 score compared to natural history GMFM-88 scores from untreated patients.

Punteggio GMFM-88 rispetto allo storico dei punteggi GMFM-88 di pazienti non trattati.

E.5.1.1

Timepoint(s) of evaluation of this end point

After 24 months of treatment compared to baseline. An interim analysis will be done after 12 months treatment.

Dopo 24 mesi di trattamento rispetto al basale. Un'analisi intermedia verrà effettuata dopo 12 mesi di trattamento.

E.5.2

Secondary end point(s)

1) Gross Motor Function Measure test (GMFM-88) individual item score 10 and 24 compared to natural history scores from untreated patients.
2) Age equivalent (AE) score from the BSID compared to natural history AE scores from untreated patients.
3) Serum T3 (efficacy), peripheral thyroid hormone TH status (serum SHBG; serum creatine kinase, creatinine, blood pressure and body weight) (efficacy).

1. Punteggi individuali GMFM-88 per le voci 10 e 24 rispetto allo storico dei punteggi di pazienti non trattati.
2. Punteggio equivalente di età (AE) dal BSID rispetto allo storico dei punteggi AE di pazienti non trattati
3. T3 sierico (efficacia), stato dell'ormone tiroideo periferico (SHBG sierico; creatina chinasi sierica, creatinina, pressione sanguigna e peso corporeo) (efficacia).

E.5.2.1

Timepoint(s) of evaluation of this end point

After 24 months of treatment compared to baseline. An interim analysis will be done after 12 months treatment.

Dopo 24 mesi di trattamento rispetto al basale. Un'analisi intermedia verrà effettuata dopo 12 mesi di trattamento.

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.7.1

Other trial design description

Tiratricol will be administered to all patients, orally in an individual dose titrated based on seru

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

Tiratricol verrà somministrato a tutti i pazienti, per via orale in una singola dose titolata in bas

Tiratricol will be administered to all patients, orally in an individual dose titrated based on seru

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

France

Germany

Italy

Netherlands

United Kingdom

Czechia

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

Yes

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children 0-30 months of age.

Bambini da 0 a 30 mesi

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Patients will be offered treatment in a follow up protocol after completion of the trial.

Ai pazienti verrà offerto un trattamento in un protocollo di follow-up dopo il completamento della sperimentazione.

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

2020-04-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-30

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

Stránka klinických studií Nct

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence