Clinical Trials Register

Summary
EudraCT Number:	2017-002820-26
Sponsor's Protocol Code Number:	ALXN1210-PNH-304
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-01-12
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

France - ANSM

A.2

EudraCT number

2017-002820-26

A.3

Full title of the trial

A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Étude de phase 3 en ouvert portant sur l’ALXN1210 chez les enfants et adolescents atteints d’hémoglobinurie paroxystique nocturne (HPN)

A.3.1

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

A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Étude de phase 3 en ouvert portant sur l’ALXN1210 chez les enfants et adolescents atteints d’hémoglobinurie paroxystique nocturne (HPN)

A.4.1

Sponsor's protocol code number

ALXN1210-PNH-304

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/199/2017

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	+33147100606
B.5.5	Fax number	+33147100611
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.3.2	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	ALXN1210
D.3.9.3	Other descriptive name	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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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)

Hémoglobinurie paroxystique nocturne (HPN)

E.1.1.1

Medical condition in easily understood language

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Hémoglobinurie paroxystique nocturne (HPN)

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	20.1
E.1.2	Level	PT
E.1.2	Classification code	10034042
E.1.2	Term	Paroxysmal nocturnal haemoglobinuria
E.1.2	System Organ Class	10038359 - Renal and urinary 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

The purpose of this study is to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ALXN1210 in pediatric patients with paroxysmal nocturnal hemoglobinuria (PNH)

L’objectif principal de cette étude est d’évaluer la pharmacocinétique (PK), la pharmacodynamique (PD), la sécurité et l’efficacité de l’ALXN1210 chez les patients pédiatriques atteints d’hémoglobinurie paroxystique nocturne (HPN).

E.2.2

Secondary objectives of the trial

Not Applicable

Non applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients from birth up to < 18 years of age and weighing ≥ 5 kg at the time of consent.
2. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry
3. For patients not currently treated with eculizumab, 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 for patients not being treated with eculizumab at screening and LDH level ≤ 1.5 × ULN for patients being treated with eculizumab.
5. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae

1. Patients de sexe masculin et féminin âgés de < 18 ans et pesant ≥ 5 kg au moment du consentement.
2. Un diagnostic documenté d’HPN, confirmé par une évaluation par cytométrie en flux de haute sensibilité
3. Chez les patients qui ne sont pas actuellement traités par un inhibiteur du complément, présence d’un ou plusieurs signes ou symptômes liés à l’HPN suivants dans les 3 mois qui ont précédé la sélection : fatigue, hémoglobinurie, douleurs abdominales, essoufflement (dyspnée), anémie, antécédents d’événement indésirable vasculaire majeur (y compris thrombose), dysphagie ou dysfonction érectile, ou antécédents de transfusion de concentré de GR due à l’HPN.
4. Taux suivant de lactate déshydrogénase (LDH) à la selection pour les patients non traités actuellement par de l’éculizumab, taux de LDH ≥ 1,5 × la limite supérieure normale (LSN) et LDH ≤ 1,5 × LSN pour les patients prenant actuellement de l’éculizumab
5. Pour réduire le risque d’infection à méningocoques (Neisseria meningitidis), tous les patients doivent avoir été vaccinés contre les infections à méningocoques dans les 3 ans qui ont précédé le début de la prise du médicament à l’étude ou au moment de celui-ci. Les patients doivent avoir été vaccinés contre l’Haemophilus influenzae de type b (Hib) et le Streptocoque pneumoniae conformément aux recommandations nationales et locales en matière de calendrier vaccinal, le cas échéant.

E.4

Principal exclusion criteria

1. Platelet count < 30,000/mm (30x109/L) at screening.
2. Absolute neutrophil count < 500 µL (0.5 x109/L) at screening
3. History of Bone Marrow transplantation
4. History of N. meningitidis infection
5. History of unexplained, recurrent infection

1. Numération plaquettaire < 30 000/mm3 (30 × 109/l) à la sélection
2. Numération absolue de neutrophiles < 500/μl (0,5 × 109/l) lors de la sélection
3. Antécédents de greffe de moelle osseuse
4. Antécédents d’infection par N. meningitidis
5. Antécédents d’infection récurrente inexpliquée

E.5 End points

E.5.1

Primary end point(s)

PK/PD parameters (trough and peak)
• PK: maximum serum concentration (Cmax), trough serum concentration (measured at end of dosing interval at steady state; Ctrough), accumulation ratio
• PD: change in free C5 concentrations and in chicken red blood cell (cRBC) hemolytic activity over time)

Paramètres PK/PD (niveau minimal et pic)
• PK : concentration sérique maximale (Cmax), concentration sérique minimale (mesurée à la fin de l’intervalle posologique à l’état d’équilibre, Cmin), rapport d’accumulation
• PD : évolution de la concentration de C5 libre et de l’activité hémolytique sur les globules rouges de poulet (GRp) au fil du temps

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline and Weeks 2, 10, 18, and 26

Visite initiale et semaines 2, 10, 18 et 26

E.5.2

Secondary end point(s)

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

- Évolution en pourcentage du LDH
- Évitement de transfusion (ET)

E.5.2.1

Timepoint(s) of evaluation of this end point

26 Weeks

Semaine 26

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

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

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

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

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 in the extension period

Dernière visite du dernier patient

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

Number of subjects for this age range:

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

Children to be enrolled. The parent or legal guardian will provide informed consent

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 return to the care of his/her physician.

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

2018-01-04

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-08-25

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