Clinical Trials Register

Summary
EudraCT Number:	2017-003372-31
Sponsor's Protocol Code Number:	LJ401-BT01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-07
Trial results	View 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-003372-31

A.3

Full title of the trial

A Multi-center, Randomized, Open-Label, Parallel-Group Study with LJPC-401 for the Treatment of Myocardial Iron Overload in Adult Patients with Transfusion-Dependent Beta Thalassemia

Studio multicentrico, randomizzato, in aperto, a gruppi paralleli con LJPC-401 per il trattamento del sovraccarico di ferro miocardico in pazienti adulti con talassemia beta trasfusione-dipendente

A.3.1

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

A multi-center clinical study to determine the effects of LJPC-401 on iron in the heart muscle in patients with beta-thalassemia who are treated with routine blood transfusions

Studio clinico multicentrico per valutare gli effetti di LJPC-401 sul ferro nel muscolo cardiaco in pazienti con beta talassemia trattati di routine con trasfusioni di sangue

A.3.2

Name or abbreviated title of the trial where available

A multi-center clinical study to determine the effects of LJPC-401 on iron in the heart muscle in pa

Studio clinico multicentrico per valutare gli effetti di LJPC-401 sul ferro nel muscolo cardiaco in

A.4.1

Sponsor's protocol code number

LJ401-BT01

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	LA JOLLA PHARMACEUTICAL COMPANY
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	La Jolla Pharmaceutical Company
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	La Jolla Pharmaceutical Company
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	4550 Towne Centre Ct
B.5.3.2	Town/ city	San Diego
B.5.3.3	Post code	92121
B.5.3.4	Country	United States
B.5.4	Telephone number	0018584336908
B.5.5	Fax number	0000000000000
B.5.6	E-mail	lajollaregulatoryaffairs@ljpc.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/3/15/1555
D.3 Description of the IMP
D.3.1	Product name	LJPC-401
D.3.2	Product code	LJPC-401
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Epcidina-25 (umana)
D.3.9.1	CAS number	342809-17-0
D.3.9.2	Current sponsor code	hepcidin-25 acetate, Synthetic human hepcidin
D.3.9.3	Other descriptive name	Hepcidin-25 (human)
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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

Transfusion-dependent beta thalassemia with myocardial iron overload

Talassemia beta trasfusione dipendente, con sovraccarico di ferro miocardico

E.1.1.1

Medical condition in easily understood language

Increased amount of iron in the heart muscle (iron overload) as a result of blood transfusions

Aumentato livello di ferro nel muscolo cardiaco (sovraccarico di ferro) come risultato della trasfusione di sangue

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10005329
E.1.2	Term	Blood and lymphatic system disorders
E.1.2	System Organ Class	10005329 - Blood and lymphatic system 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

Efficacy on cardiac iron as measured by cardiac T2* MRI in adult patients with transfusion-dependent beta thalassemia.

Efficacia sui livelli cardiaco di ferro misurati mediante mediante risonanza magnetica (RM) cardiaca in sequenza T2* in pazienti adulti affetti da talassemia beta trasfusione-dipendente.

E.2.2

Secondary objectives of the trial

¿Safety and tolerability in adult patients with transfusion-dependent beta thalassemia
¿TSAT
¿Immunogenicity (anti-LJPC-401 antibodies)

¿Sicurezza e tollerabilit¿ in pazienti adulti con talassemia beta trasfusione-dipendente;
¿Effetto sulla saturazione della transferrina (TSAT%);
¿Immunogenicit¿ (anticorpi anti-LJPC-401).

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: ¿Pharmacokinetic (PK) Sub-study¿
An optional PK substudy will be performed in a subset of subjects who provide a separate informed consent (approximately 20).
Blood sampling for PK will be taken at first dose at Hour -24, Hour 0, and post-dose Hours 0.5, 2, 4, 8, 12 (optional), 24, 48, and 168 (pre-dose
before next weekly dosing). Hour 0 and Hour 168 can be combined with the immunogenicity and PK sample collected at Weeks 27 and 28 for Group A and Weeks 1 and 2 for Group B.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: ¿Sottostudio di farmacocinetica (PK)¿
Verr¿ svolto un sottostudio opzionale di PK in un sottogruppo di soggetti che forniranno in consenso informato a parte (approssimativamente 20 soggetti). Verranno prelevati campioni di sangue alla prima somministrazione 24 ore prima della stessa, all¿ora 0 e post-somministrazione a 0,5, 2, 4, 8, 12 (opzionale), 24, 48 e 168 ore (pre-dose prima della somministrazione settimanale successiva). I prelievi all¿ora 0 e all¿ora 168 possono essere combinati con i prelievi per l¿immunogenicit¿ e la PK raccolti alla settimana 27 e 28 per il Gruppo A ed alla settimana 1 e 2 per il Gruppo B.

E.3

Principal inclusion criteria

1. Patients = 18 years of age with transfusion-dependent beta thalassemia and must have been transfused within 1 month of randomization.
2. Patients must have a TSAT = 50% at Screening.
3. Two separate cardiac MRIs should be greater than 3 weeks but no more than 3 months apart that both demonstrate cardiac T2* MRI of 6 to 35 (msec) with no more than a 10% difference between the first and second reading.
4. Patients must be receiving iron chelation therapy for a minimum of 1 year and be on a stable dose of maximally tolerated iron chelation therapy for a minimum of 8 weeks prior to study and expected to remain stable during study.
5. Female patients must be of non-childbearing potential, or using a highly effective method of contraception during participation in the study. Highly effective methods of contraception are defined as those, alone or in combination, that result in a low failure rate when used consistently and correctly. These include: surgical sterility (vasectomy, bilateral tubal ligation, or hysterectomy); hormonal intrauterine device (IUD); hormonal intrauterine system (IUS), implants, or injections; consistent use of an approved oral contraceptive pill (combined progestin/estrogen pill or progestin-only pill); combined intravaginal or transdermal method; and abstinence.
6. Female patients of childbearing potential must have a negative serum pregnancy test at Screening, and negative urine pregnancy test at Week 1 (ie, prior to initial dosing of study drug).
7. Male patients must be surgically sterile, or using a highly effective method of contraception during participation in the study. Highly effective methods of contraception are defined as those, alone or in combination, that result in a low failure rate when used consistently and correctly.
8. Patient must be willing and able to provide written informed consent.

1. Pazienti di età =18 anni con talassemia beta trasfusione-dipendente che devono essere stati trasfusi entro 1 mese dalla randomizzazione.
2. I pazienti devono avere una TSAT =50% allo screening.
3. Due RM cardiache separate, eseguite a distanza di oltre 3 settimane ma non oltre i 3 mesi l’una dall’altra, che dimostrino entrambe un valore di RM cardiaca in sequenza T2* da 6 a 35 (ms) con una differenza non superiore al 10% tra la prima e la seconda lettura.
4. I pazienti devono aver ricevuto una terapia ferrochelante per almeno 1 anno, devono essere in trattamento con terapia ferrochelante alla massima dose stabile tollerata per almeno 8 settimane prima dello studio, e con l’aspettativa di rimanere ad una dose stabile durante lo studio.
5. I pazienti di sesso femminile non devono essere in età fertile, oppure devono adottate un metodo contraccettivo altamente efficace durante la loro partecipazione allo studio. Per metodi contraccettivi altamente efficaci si intendono quei metodi che, da soli o in combinazione, sono caratterizzati da un basso tasso di insuccesso se utilizzati in maniera costante e corretta. Tra questi vi sono: sterilizzazione chirurgica (vasectomia, legatura tubarica bilaterale o isterectomia); dispositivo intrauterino (IUD) ormonale; sistema intrauterino (IUS), impianti o iniezioni ormonali; uso costante di una pillola contraccettiva orale approvata (pillola contenente la combinazione progestinico/estrogeno o pillola contenente solo progestinico); metodo intravaginale o transdermico combinato; astinenza.
6. I pazienti di sesso femminile in età fertile devono risultare negativi al test di gravidanza sul siero allo screening e al test di gravidanza sulle urine alla Settimana 1 (ovvero, prima della somministrazione iniziale del farmaco dello studio).
7. I pazienti di sesso maschile devono essere chirurgicamente sterili, oppure devono utilizzare un metodo contraccettivo altamente efficace durante la loro partecipazione allo studio. Per metodi contraccettivi altamente efficaci si intendono quei metodi che, da soli o in combinazione, sono caratterizzati da un basso tasso di insuccesso se utilizzati in maniera costante e corretta.
8. Il paziente deve essere disposto e in grado di fornire il consenso informato scritto.

E.4

Principal exclusion criteria

1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
2. Pregnant or lactating women.
3. Patients taking an immunosuppressive agent (excluding topical over-the-counter steroids) or have a planned surgery (excluding dental surgery or simple dermatologic procedures) during participation in this study or within 2 weeks prior to randomization.
4. Patients participating in an unapproved investigational drug or investigational therapeutic device study within 30 days prior to randomization, ie, there must be at least 30 days in between the last dose on a prior study and randomization on this trial.
5. Patients with a concomitant disease, disability or condition, including laboratory abnormality, which may interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the patient in this study, including, but not limited to, alcohol dependency or abuse, drug dependency or abuse, or psychiatric disease.
6. Patients who are unwilling or unable to comply with the study protocol requirements.
7. Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
8. Patients with Child Pugh class C cirrhosis or liver failure.
9. Patients with severe congestive heart failure (New York Heart Association [NYHA] = Class 4).
10. Use of erythropoiesis stimulating agents in the past 3 months prior to study entry.
11. History of allergic reaction to hepcidin or excipients.
12. Contraindication to MRI scanning.

1. Qualsiasi condizione medica, anomalia di laboratorio o malattia psichiatrica significativa che impedisca al paziente di partecipare allo studio.
2. Donne in stato di gravidanza o allattamento.
3. Pazienti che assumono agenti immunosoppressivi (esclusi steroidi topici da banco) o che prevedono di sottoporsi a intervento chirurgico (esclusi interventi odontoiatrici o semplici procedure dermatologiche) durante la loro partecipazione allo studio o nelle 2 settimane precedenti la randomizzazione.
4. Pazienti che partecipano a uno studio non approvato di un farmaco sperimentale o dispositivo terapeutico sperimentale nei 30 giorni precedenti la randomizzazione; il che significa che devono essere trascorsi almeno 30 giorni tra l’ultima dose in un precedente studio e la randomizzazione in questa sperimentazione.
5. Pazienti con una malattia, invalidità o condizione concomitante, inclusa un’anomalia di laboratorio, che potrebbe interferire con la conduzione dello studio o che, a giudizio dello sperimentatore, potrebbe comportare un rischio inaccettabile per il paziente in questo studio, compresi, ma non limitati a, dipendenza o abuso di alcol, dipendenza o abuso di sostanze stupefacenti o malattie psichiatriche.
6. Pazienti riluttanti o impossibilitati ad attenersi ai requisiti previsti dal protocollo dello studio.
7. Infezione nota causata da virus dell’epatite B, epatite C o virus dell’immunodeficienza umana (HIV).
8. Pazienti con cirrosi o insufficienza epatica di classe C secondo la classificazione di Child-Pugh.
9. Pazienti con insufficienza cardiaca congestizia grave (classe 4 secondo l’Associazione cardiologica di New York [New York Heart Association, NYHA]).
10. Uso di agenti stimolanti l’eritropoiesi nei 3 mesi precedenti l’ingresso nello studio.
11. Anamnesi di reazione allergica all’epcidina o agli eccipienti.
12. Controindicazione alla RM.

E.5 End points

E.5.1

Primary end point(s)

The mean change from baseline (Screening) in intrapatient cardiac iron level as measured by T2* MRI at week 26.

Variazione media rispetto al basale (screening) nel livello intra-paziente di ferro cardiaco misurato mediante RM cardiaca in sequenza T2* alla Settimana 26.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 26 (comparing 26 weeks of Standard of Care (SOC) [Group A] to 26 weeks of SOC plus LJPC-401 [Group B]).

Settimana 26 (confrontando 26 settimane di SOC [Gruppo A] con 26 settimane di SOC più LJPC-401 [Gruppo B]).

E.5.2

Secondary end point(s)

1. Mean change from baseline (Screening) in intrapatient cardiac iron level as measured by cardiac T2* MRI at week 52
2. Mean change from baseline (Screening) in intrapatient cardiac iron level as measured by cardiac T2* MRI at post-baseline visits other than
Week 26 and Week 52.
3. Change in time-weighted TSAT%.
4. The proportion of patients with an increase of at least 20% compared to baseline (Screening) in the T2* level as measured by cardiac MRI.

1. Variazione media rispetto al basale (screening) nel livello intra-paziente di ferro cardiaco misurato mediante RM cardiaca in sequenza T2* alla Settimana 52.
2. Variazione media rispetto al basale (screening) nel livello intra-paziente di ferro cardiaco misurato mediante RM cardiaca in sequenza T2* alle visite post-basale diverse da quelle previste per la Settimana 26 e Settimana 52.
3. Variazione nella TSAT% ponderata in base al tempo.
4. Percentuale di pazienti con un incremento di almeno il 20% rispetto al basale (screening) nel livello di T2* misurato mediante RM cardiaca.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 52 (comparing delayed treatment/Group A [26 weeks of SOC followed by 26 weeks of SOC plus LJPC-401] to 52 weeks of immediate treatment/Group B [SOC + LJPC 401]).

Settimana Settimana 52 (confrontando il trattamento ritardato/Gruppo A [26 settimane di SOC seguite da 26 settimane di SOC pi¿ LJPC-401] con 52 settimane di trattamento immediato/Gruppo B [SOC + LJPC-401]).

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

Yes

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Trattamento immediato in confronto al trattamento ritardato.

Immediate treatment versus delayed treatment.

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

Lebanon

Thailand

Turkey

United States

Cyprus

Greece

Italy

United Kingdom

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

Last patient last visit.

Ultima vista dell'ultimo paziente.

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:

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

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)

None

Nessuno

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

2018-03-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-01-17

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials