Clinical Trials Register

Summary
EudraCT Number:	2021-001831-17
Sponsor's Protocol Code Number:	MT-7117-A-301
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:	2021-12-06
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

2021-001831-17

A.3

Full title of the trial

A Phase 3, Multicenter, Open-label, Long-term, Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)

Studio di estensione di fase III, multicentrico, in aperto, a lungo termine, per valutare la sicurezza e la tollerabilità di dersimelagon orale (MT-7117) in soggetti con protoporfiria eritropoietica (EPP) o protoporfiria legata all’X (XLP)

A.3.1

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

An open label, long-term extension study to determine how safe and tolerable oral Dersimelagon is in subjects with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)

Uno studio di estensione in aperto a lungo termine per determinare quanto sia sicuro e tollerabile il dersimelagon orale in soggetti con protoporfiria eritropoietica (EPP) o protoporfiria legata all'X (XLP)

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

MT-7117-A-301

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	Mitsubishi Tanabe Development America Inc.
B.1.3.4	Country	United States
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	Mitsubishi Tanabe Pharma Development America, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mitsubishi Tanabe Pharma Europe LTD (MTPE)
B.5.2	Functional name of contact point	Andy Bryson
B.5.3	Address:
B.5.3.1	Street Address	Dashwood House, 69 Old Broad Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	EC2M1QS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	004402070655035
B.5.5	Fax number	000000
B.5.6	E-mail	abryson@mt-pharma-eu.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dersimelagon
D.3.2	Product code	[MT-7117]
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	Dersimelagon
D.3.9.1	CAS number	1835256-48-8
D.3.9.2	Current sponsor code	MT-7117
D.3.9.3	Other descriptive name	MT-7117
D.3.9.4	EV Substance Code	SUB181965
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	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

Erythropoietic Protoporphyria or X-Linked Protoporphyria

Protoporfiria Eritropoietica (EPP) o Protoporfiria legata all’X (XLP)

E.1.1.1

Medical condition in easily understood language

Rare metabolic diseases caused by the alteration of some enzymes related to the heme group.

Malattie metaboliche rare causate dall'alterazione di alcuni enzimi correlati al gruppo eme.

E.1.1.2

Therapeutic area

Diseases [C] - Symptoms and general pathology [C23]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	24.0
E.1.2	Level	LLT
E.1.2	Classification code	10015289
E.1.2	Term	Erythropoietic protoporphyria
E.1.2	System Organ Class	100000004850

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 long-term safety and tolerability of oral dersimelagon.

Valutare la sicurezza e la tollerabilità a lungo termine di dersimelagon orale.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects provided written informed consent to participate. For adolescent subjects, both adolescent assent and parental consent will be provided.
2. Subjects who complete MT-7117-G01 (complete through Week 58 [Visit 12])
3. Subjects have a body weight of >=30 kg.
4. Subjects are willing and able to travel to the study sites for all scheduled visits.
5. In the Investigator's opinion, subject can understand the nature of the study and any risks involved in participation, and is willing to cooperate and comply with the protocol restrictions and requirements (including travel).
6. Female subjects who are non-lactating and have a negative urine pregnancy test at baseline visit prior to receiving the first dose of study drug.
7. Female subjects of childbearing potential and male subjects with partner of childbearing potential must agree to use 2 effective methods of contraception including barrier method (especially for female subjects, one method must be highly effective method) as described in Section 4.6.1.

1. Fornire il consenso informato scritto alla partecipazione. Per i soggetti adolescenti, dovrà essere fornito sia l’assenso dell’adolescente sia il consenso dei genitori;
2. Soggetti che hanno completato lo studio MT-7117-G01 [fino alla Settimana 58 (Visita 12)];
3. Peso corporeo >=30 kg;
4. Volontà e possibilità di viaggiare per recarsi presso i centri dello studio per tutte le visite programmate;
5. Capacità di comprendere, a giudizio dello sperimentatore, la natura dello studio e gli eventuali rischi connessi alla partecipazione e volontà di cooperare e rispettare le restrizioni e i requisiti del protocollo (compresi quelli relativi ai viaggi);
6. Soggetti di sesso femminile che non stanno allattando con latte materno e che presentano un test di gravidanza delle urine negativo alla visita basale prima di ricevere la prima dose del farmaco in studio;
7. I soggetti di sesso femminile in età fertile e i soggetti di sesso maschile con partner in età fertile devono acconsentire a utilizzare 2 metodi contraccettivi efficaci, incluso un metodo barriera (specialmente per le donne, uno dei metodi deve essere altamente efficace), come descritto nel paragrafo 4.6.1.

E.4

Principal exclusion criteria

English 1. History or presence of photodermatoses other than EPP or XLP.
2. Presence or history of any hepatobiliary disease at screening determined as clinically significant by the Investigator after the discussion with the Sponsor Medical Monitor.
3. Subjects with AST, ALT, ALP =3.0 × upper limit of normal (ULN) or total bilirubin > 1.5 × ULN at Screening.
4. Subjects with or having a history (in the last 2 years) of excessive alcohol intake in the opinion of the Investigator.
5. History of melanoma.
6. Presence of melanoma and/or lesions suspicious for melanoma at
Screening.
7. History of familial melanoma (defined as having 2 or more first-degree relatives, such as parents, sibling and/or child).
8. Presence of squamous cell carcinoma, basal cell carcinoma, or other malignant skin lesions. Any suspicious lesions or nevi will be evaluated. If the suspicious lesion or nevi cannot be resolved through biopsy or excision, the subject will be excluded from the study.
9. History or presence of psychiatric disease judged to be clinically significant by the Investigator and which may interfere with the study evaluation and/or safety of the subjects.
10. Presence of clinically significant acute or chronic renal disease based upon the subject's medical records including hemodialysis; an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 as calculated by the CKD-EPI creatinine equation (2009) for adults and by the Schwartz creatinine equation for adolescents (2009) (Section 16.2, Appendix 2). MDRD can be used for adults per local recommendations.
11. Presence of any clinically significant disease or laboratory abnormality which, in the opinion of the Investigator, can interfere with the study objectives and/or safety of the subjects.
12. Female subjects who are pregnant, lactating, or intending to become pregnant during the study.
13. Treatment with phototherapy or afamelanotide within 3 months before baseline (Visit 2).
14. Treatment with cimetidine or antioxidant agents at doses which, in the opinion of the Investigator, may affect study endpoints (including but not limited to beta-carotene, cysteine, pyridoxine) within 4 weeks before baseline (Visit 2).
15. Chronic treatment with any scheduled analgesic agents including, but not limited to, opioids and opioid derivatives such as morphine, hydrocodone, oxycodone, fentanyl, or their combination with other unscheduled analgesics or non-steroidal anti-inflammatory drug (Percocet and Vicodin-like prescription drugs) within 4 weeks before baseline (Visit 2). Acute use of scheduled narcotics greater than 3 months prior to baseline, overthe- counter medications (OTCs), such as non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin for analgesia, or prior temporary use of scheduled agents within 3 months of baseline (Visit 2) are not excluded.
16. Treatment with any drugs or supplements which, in the opinion of the Investigator, can interfere with the objectives of the study or safety of the subjects.
17. Previous treatment with any investigational agent other than dersimelagon within 12 weeks before Screening OR 5 half-lives of the investigational product (whichever is longer).
Please refer to the Protocol for further exclusion criteria.

1. Anamnesi o presenza di fotodermatosi diverse da EPP o XLP;
2. Presenza o anamnesi di qualsiasi malattia epatobiliare allo screening, ritenuta clinicamente significativa dallo sperimentatore dopo discussione con il Monitor clinico dello
Sponsor;
3. Soggetti con AST, ALT, ALP >=3,0 × limite superiore della norma (ULN) o bilirubina totale > 1,5 × ULN allo screening;
4. Soggetti con assunzione eccessiva di alcol, attuale o passata (negli ultimi 2 anni), secondo il giudizio dello sperimentatore;
5. Anamnesi di melanoma;
6. Presenza di melanoma e/o sospette lesioni melanomatose allo screening;
7. Anamnesi di melanoma familiare (definito come presenza della malattia in 2 o più parenti di primo grado, come genitori, fratelli e/o figli);
8. Presenza di carcinoma a cellule squamose, carcinoma basocellulare o altre lesioni cutanee maligne. Eventuali lesioni o nevi sospetti saranno valutati. Se la lesione o i nevi sospetti non si risolvono mediante biopsia o escissione, il soggetto sarà escluso dallo studio;
9. Anamnesi o presenza di malattia psichiatrica ritenuta clinicamente significativa dallo sperimentatore e che potrebbe interferire con la valutazione dello studio e/o la sicurezza dei soggetti;
10. Presenza di malattia renale acuta o cronica clinicamente significativa in base alle cartelle cliniche del soggetto, compresa emodialisi; una velocità di filtrazione glomerulare stimata (eGFR) <60 mL/min/1,73 m2 calcolata mediante equazione della creatinina di CKD-EPI (2009) per gli adulti e
mediante equazione della creatinina di Schwartz per gli adolescenti (2009) (paragrafo 16.2, Appendice 2). Per gli adulti può essere usata l’equazione MDRD in base alle raccomandazioni locali;
11. Presenza di qualsiasi patologia clinicamente significativa o anomalia di laboratorio che, a giudizio dello sperimentatore, potrebbe interferire con gli obiettivi dello studio e/o la sicurezza dei soggetti;
12. Soggetti di sesso femminile in stato di gravidanza, allattamento con latte materno o che intendono iniziare una gravidanza durante lo studio;
13. Trattamento con fototerapia o afamelanotide nei 3 mesi precedenti il basale (Visita 2);
14. Trattamento con cimetidina o agenti antiossidanti a dosi che, a giudizio dello sperimentatore, potrebbero influenzare gli endpoint dello studio (inclusi, a titolo esemplificativo, betacarotene, cisteina, piridossina) nelle 4 settimane precedenti il basale (Visita 2);
15. Trattamento cronico con qualsiasi analgesico programmato, inclusi, a titolo esemplificativo, oppioidi e derivati oppioidi come morfina, idrocodone, ossicodone, fentanil, o la loro combinazione con altri analgesici o farmaci antinfiammatori non steroidei non programmati (farmaci su prescrizione simili a Percocet e Vicodin) nelle 4 settimane precedenti il basale (Visita 2). L’uso in acuto di narcotici programmati più di 3 mesi prima del basale (Visita 2), di farmaci da banco (OTC) come i farmaci antinfiammatori non steroidei (FANS) o l’aspirina per l’analgesia, o il precedente uso temporaneo di agenti programmati nei 3 mesi precedenti il basale (Visita 2) non è escluso;
16. Trattamento con qualsiasi farmaco o integratore che, a giudizio dello sperimentatore, può interferire con gli obiettivi dello studio o con la sicurezza dei soggetti;
17. Precedente trattamento con qualsiasi agente sperimentale diverso da dersimelagon nelle 12 settimane precedenti lo screening oppure 5 emivite del prodotto sperimentale (a seconda di quale periodo è superiore);
Per ulteriori criteri di esclusione si prega di fare riferimento al Protocollo.

E.5 End points

E.5.1

Primary end point(s)

1. Treatment-emergent adverse events (TEAEs) (including serious adverse events [SAEs] and adverse events of special interest [AESIs]).
2. Physical examination.
3. Vital signs (blood pressure, respiratory rate, pulse rate, and body temperature).
4. Clinical laboratory examinations (hematology, coagulation, biochemistry, and
urinalysis), including liver function markers (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], direct and total bilirubin).
5. 12-lead electrocardiogram (ECG) parameters.
6. Nevi appearance (assessed by a dermatologist or other qualified site staff). Any nevi undergoing change of clinical concern during active treatment will be biopsied for follow up and evaluated by the central pathology lab.

1. Eventi avversi emergenti dal trattamento (TEAE) [compresi eventi avversi gravi (SAE) ed eventi avversi di interesse speciale (AESI)];
2. Esame obiettivo;
3. Parametri vitali (pressione arteriosa, frequenza respiratoria, frequenza cardiaca e temperatura corporea);
4. Esami clinici di laboratorio (ematologia, coagulazione, biochimica e analisi delle urine), inclusi i marcatori di funzionalità epatica (ALT, AST, GGT, ALP, bilirubina diretta e totale);
5. Parametri dell’elettrocardiogramma (ECG) a 12 derivazioni;
6. Aspetto dei nevi (valutato da un dermatologo o da altro personale qualificato del centro). Qualsiasi nevo che subisce un cambiamento che desti preoccupazione clinica durante il trattamento attivo sarà sottoposto a follow-up mediante biopsia e valutato dal laboratorio centrale di patologia

E.5.1.1

Timepoint(s) of evaluation of this end point

SAE & Clinical lab - at visit 1-8
Physical examination & Vital signs - at visit 1,2,3,5 &7
ECG - visit 1
Nevi appearance - at visit 1,2,3,5,7,& 8

SAE e analisi cliniche di laboratorio – alle visite 1-8
Esame obiettivo e parametri vitali – alle visite 1, 2, 3, 5 e 7
ECG – alla visita 1
Aspetto dei nevi – alle visite 1, 2, 3, 5, 7, e 8

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

E.6.4

Safety

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tollerabilità

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

E.8.1.2

Open

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

Studio di estensione a lundo termine, in aperto

Long term open extension study

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

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

Australia

Canada

Germany

Italy

Japan

Norway

Spain

Sweden

United Kingdom

United States

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)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

138

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Adolescents

Adolescenti

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

184

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)

None

Nessuno

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	American Porphyria Foundation
G.4.3.4	Network Country	United States

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-03-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-04-12

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

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Orphan Designation Number:
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