Clinical Trials Register

Summary
EudraCT Number:	2016-002025-11
Sponsor's Protocol Code Number:	ALXN1210-PNH-301
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:	2021-06-17
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-002025-11

A.3

Full title of the trial

A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Na¿ve Adult Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

STUDIO DI FASE 3, RANDOMIZZATO, IN APERTO, CON CONTROLLO ATTIVO DI ALXN1210 RISPETTO A ECULIZUMAB IN PAZIENTI ADULTI AFFETTI DA EMOGLOBINURIA PAROSSISTICA NOTTURNA (EPN) NA¿VE AL TRATTAMENTO CON INIBITORI DEL COMPLEMENTO

A.3.1

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

Study of ALXN1210 compared to eculizumab in PNH patients who have never been treated with a complement inhibitor.

Studio su ALXN1210 rispetto a eculizumab in pazienti con EPN che non sono mai stati trattati con inibitori del complemento.

A.3.2

Name or abbreviated title of the trial where available

Study of ALXN1210 compared to eculizumab in PNH patients who have never been treated with a compleme

Studio su ALXN1210 rispetto a eculizumab in pazienti con EPN che non sono mai stati trattati con ini

A.4.1

Sponsor's protocol code number

ALXN1210-PNH-301

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02946463

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	ALEXION PHARMACEUTICALS INCORPORATED
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	Alexion Pharmaceuticals Incorporated
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	Alexion Europe SAS
B.5.2	Functional name of contact point	European Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	1-15 Avenue Edouard Belin
B.5.3.2	Town/ city	Rueil-Malmaison
B.5.3.3	Post code	92500
B.5.3.4	Country	France
B.5.4	Telephone number	0033147100606
B.5.5	Fax number	0033147100611
B.5.6	E-mail	clinicaltrials.eu@alexion.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/3/16/1661
D.3 Description of the IMP
D.3.1	Product name	ALXN1210
D.3.2	Product code	ALXN1210
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ALXN1210
D.3.9.4	EV Substance Code	SUB172162
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	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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	Soliris
D.2.1.1.2	Name of the Marketing Authorisation holder	Alexion Europe SAS
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/166
D.3 Description of the IMP
D.3.1	Product name	ALXN1210
D.3.2	Product code	[ALXN1210]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ECULIZUMAB
D.3.9.1	CAS number	219685-50-4
D.3.9.2	Current sponsor code	ND
D.3.9.4	EV Substance Code	SUB25187
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	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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

Paroxysmal Nocturnal Hemoglobinuria (PNH)

EMOGLOBINURIA PAROSSISTICA NOTTURNA (EPN)

E.1.1.1

Medical condition in easily understood language

Paroxysmal Nocturnal Hemoglobinuria (PNH)

EMOGLOBINURIA PAROSSISTICA NOTTURNA (EPN)

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10055629
E.1.2	Term	Paroxysmal nocturnal hemoglobinuria
E.1.2	System Organ Class	100000004857

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

The purpose of this study is to assess ALXN1210 compared to eculizumab in adult patients with PNH who have never been treated with a complement inhibitor.

L¿obiettivo primario di questo studio ¿ valutare la ALXN1210 rispetto a eculizumab in pazienti adulti affetti da EPN che non sono mai stati sottoposti a trattamento con inibitori del complemento.

E.2.2

Secondary objectives of the trial

- safety and tolerability of ALXN1210
- efficacy
- PK/PD and immunogenicity
- long-term safety and efficacy
- To evaluate the safety and efficacy in patients who switch from eculizumab to ALXN1210 in the Extension Period

- sicurezza e tollerabilit¿ di ALXN1210
- efficacia
- PK/PD e immunogenicit¿
- sicurezza ed efficacia a lungo termine
- valutare la sicurezza e l'efficacia nei pazienti che passano da eculizumab a ALXN1210 nel periodo di estensione

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female = 18 years of age.
2. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
3. Presence of 1 or more of the following PNH related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin <10 g/dL), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of pRBC transfusion due to PNH.
4. LDH level = 1.5 × ULN at screening.
5. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
6. Female patients of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ALXN1210.
7. Willing and able to give written informed consent and comply with study visit schedule.

1. Soggetto di sesso maschile o femminile di almeno 18 anni di età al momento del consenso.
2. Diagnosi documentata di EPN confermata mediante citometria a flusso ad alta sensibilità
3. La presenza di 1 o più dei seguenti segni o sintomi correlati all’EPN entro 3 mesi dallo screening: affaticamento, emoglobinuria, dolore addominale, mancanza di respiro (dispnea), anemia (emoglobina <10 g/dl), anamnesi di un evento avverso vascolare maggiore (tra cui trombosi), disfagia o disfunzione erettile; oppure anamnesi di trasfusione di pRBC dovuta a EPN.
4. Livello di LDH =1,5 volte l’ULN allo screening.
5. Documentata vaccinazione contro le infezioni da meningococco entro i 3 anni precedenti o nel momento in cui si inizia l’assunzione del farmaco dello studio
6. Le pazienti in età fertile devono seguire le linee guida previste dal protocollo per evitare una gravidanza durante il trattamento e negli 8 mesi successivi all’ultima dose del farmaco dello studio.
7. I pazienti devono essere disposti a e in grado di fornire un consenso informato scritto e di rispettare tutte le visite e le procedure dello studio

E.4

Principal exclusion criteria

1. Treatment with a complement inhibitor at any time.
2. History of bone marrow transplantation.
3. Body weight < 40 kilograms.
4. Females who are pregnant, breastfeeding or who have a positive pregnancy test at screening or Day 1.
5. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.
6. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would
preclude participation.
7. Unstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need
for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).

1. Trattamento attuale o precedente con un inibitore del complemento.
2. Anamnesi di trapianto di midollo osseo.
3. Peso corporeo <40 kg allo screening.
4. Soggetti di sesso femminile in gravidanza, in allattamento o che prevedano di iniziare una gravidanza.
5. Partecipazione a un altro studio di trattamento interventistico o uso di qualsiasi terapia sperimentale nei 30 giorni precedenti all’inizio della somministrazione del farmaco dello studio il Giorno 1 di questo studio o entro 5 emivite di quel prodotto sperimentale, a seconda di quale sia maggiore.
6. Anamnesi o presenza di malattia cardiaca, polmonare, renale, endocrina o epatica maggiore (ad esempio epatite attiva) che, a giudizio dello Sperimentatore o dello Sponsor, precluda la partecipazione del paziente a una sperimentazione clinica.
7. Condizioni mediche instabili (ad es. ischemia miocardica, emorragia gastrointestinale attiva, grave insufficienza cardiaca congestizia, necessità precoce di un intervento chirurgico maggiore entro 6 mesi dalla randomizzazione, anemia cronica concomitante non correlata all’EPN)

E.5 End points

E.5.1

Primary end point(s)

- Percentage of patients who achieve transfusion avoidance (TA)
- Normalization of lactate dehydrogenase (LDH) levels

- Percentuale di pazienti che non ricevono alcuna trasfusione e non necessitano di trasfusione
- Normalizzazione dei livelli di LDH

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks

26 settimane

E.5.2

Secondary end point(s)

- Percentage change from baseline in lactate dehydrogenase ( LDH) levels
- Change from baseline in quality of life as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue
- Percentage of patients with breakthrough hemolysis
- Percentage of patients with stabilized hemoglobin

- Variazione percentuale nell¿LDH dal basale
- Cambiamento nella qualit¿ della vita (QoL) valutato mediante la Scala di valutazione funzionale della terapia per malattie croniche (FACIT)-Affaticamento
- Percentuale di pazienti con emolisi episodica
- Percentuale di pazienti con emoglobina stabilizzata

E.5.2.1

Timepoint(s) of evaluation of this end point

26 weeks

26 settimane

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)

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

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

Korea, Republic of

United States

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

The end of the study is defined as the date of the last patient¿s last visit in the Extension Period.

La fine Studio ¿ definita come la data dell'ultima visita dell'ultimo paziente nel periodo di estensione

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:

192

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

214

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 return to the care of his/her physician.

Il paziente torna alle cure del medico curante

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

2017-02-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-11

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

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