Clinical Trials Register

Summary
EudraCT Number:	2021-004253-22
Sponsor's Protocol Code Number:	ALXN2040-PNH-303
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-05-06
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

Spain - AEMPS

A.2

EudraCT number

2021-004253-22

A.3

Full title of the trial

A Long-term Extension (LTE) Study to Characterize the Safety and Efficacy of Danicopan as an Add-on Therapy to a Complement Component 5 Inhibitor (C5i) in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Previously Treated with Danicopan in an Alexion-sponsored Clinical Study.

Estudio de extensión a largo plazo (ELP) para determinar la seguridad y la eficacia del danicopán como tratamiento suplementario a un inhibidor del componente 5 (iC5) del complemento en pacientes con hemoglobinuria paroxística nocturna (HPN) previamente tratados con el danicopán en un estudio clínico patrocinado por Alexion.

A.3.1

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

A Long-term Safety and Efficacy Study of Danicopan as an Add-on Therapy to C5i in Patients with PNH.

Estudio para determinar la eficacia y la seguridad a largo plazo del danicopán como tratamiento suplementario a iC5 en pacientes con HPN.

A.4.1

Sponsor's protocol code number

ALXN2040-PNH-303

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 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	Alexion Pharmaceuticals
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	103-105 Rue Anatole France
B.5.3.2	Town/ city	Levallois-Perret
B.5.3.3	Post code	92300
B.5.3.4	Country	France
B.5.4	Telephone number	0033787148158
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/3/17/1946
D.3 Description of the IMP
D.3.1	Product name	Danicopan
D.3.2	Product code	ALXN2040
D.3.4	Pharmaceutical form	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	DANICOPAN
D.3.9.1	CAS number	1903768-17-1
D.3.9.2	Current sponsor code	ALXN2040
D.3.9.3	Other descriptive name	DANICOPAN
D.3.9.4	EV Substance Code	SUB189885
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	50
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	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	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/3/17/1946
D.3 Description of the IMP
D.3.1	Product name	Danicopan
D.3.2	Product code	ALXN2040
D.3.4	Pharmaceutical form	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	DANICOPAN
D.3.9.1	CAS number	1903768-17-1
D.3.9.2	Current sponsor code	ALXN2040
D.3.9.3	Other descriptive name	DANICOPAN
D.3.9.4	EV Substance Code	SUB189885
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	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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Paroxysmal Nocturnal Hemoglobinuria

Pacientes con hemoglobinuria paroxística nocturna.

E.1.1.1

Medical condition in easily understood language

Patients with Paroxysmal Nocturnal Hemoglobinuria

Pacientes con hemoglobinuria paroxística nocturna.

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
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

To characterize the long-term safety of treatment with danicopan as an add-on therapy to a complement component 5 inhibitor (C5i).

Determinar la seguridad a largo plazo del tratamiento con el anicopán como tratamiento suplementario a un inhibidor del componente 5 (iC5) del complemento

E.2.2

Secondary objectives of the trial

-To characterize the long-term efficacy of danicopan as an add-on therapy to a C5i
-To characterize the long-term effect of treatment with danicopan as an add-on therapy to a C5i on Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scores and on European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC-QLQ-C30) scores
-To further characterize the safety of danicopan as an add-on therapy to a C5i

- Determinar la eficacia a largo plazo del danicopán como tratamiento suplementario a un iC5
- Determinar el efecto a largo plazo del tratamiento con el danicopán como tratamiento suplementario a un iC5 según la puntuación del cuestionario de evaluación funcional del tratamiento de enfermedades crónicas (FACIT)-Cansancio y la puntuación del cuestionario de calidad de vida de la Organización Europea de Investigación y Tratamiento del Cáncer (EORTC-QLQ-C30)
- Determinar en mayor profundidad la seguridad del danicopán como tratamiento suplementario a un iC5

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- All participants who completed their participation in an Alexion sponsored clinical study with danicopan as an add on to a C5i treatment.
- Documentation of vaccination for Neisseria meningitidis: All participants must be revaccinated as per national vaccination guidelines or local practice for vaccination use with complement inhibitors.

- Todos los pacientes que hayan completado su participación en un estudio clínico esponsorizado por Alexion con danicopan como complemento de un tratamiento con C5i.
- Documentación de la vacunación contra la Neisseria meningitidis: Todos los pacientes deben ser revacunados según las directrices nacionales de vacunación o la práctica local para el uso de la vacunación con inhibidores del complemento.

E.4

Principal exclusion criteria

- Any medical condition (for example, cardiac, pulmonary, renal, oncologic, or psychiatric) that, in the opinion of the Investigator, might interfere with participation in the study, pose any added risk to the participant, or confound the assessment of the participant.
- Female participants who are pregnant, breastfeeding, or intending to conceive during the course of the study.

- Cualquier condición médica (por ejemplo, cardíaca, pulmonar, renal, oncológica o psiquiátrica) que, en opinión del investigador, pueda interferir con la participación en el estudio, suponer un riesgo añadido para el participante o confundir la evaluación del mismo.
- Pacientes femeninas que estén embarazadas, amamantando o que tengan intención de concebir durante el transcurso del estudio.

E.5 End points

E.5.1

Primary end point(s)

• Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs

•Incidencia de acontecimientos adversos surgidos durante el tratamiento (AAST) y AAST graves Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs

E.5.1.1

Timepoint(s) of evaluation of this end point

Over time throughout the study. Planned time points for all safety assessments are provided in the SoA (Section 1.3 of the protocol)

A lo largo del estudio. Los puntos de tiempo planificados para todas las evaluaciones de seguridad se proporcionan en el SoA (Sección 1.3 del protocolo).

E.5.2

Secondary end point(s)

• Change in hemoglobin (Hgb) values over time
• Change in absolute reticulocyte count over time
• Change in lactate dehydrogenase (LDH) over time
• Proportion of patients with LDH ≤ 1.5 × upper limit of normal (ULN) over time
• Proportion of patients with transfusion avoidance (TA), defined as patients who remain transfusion free and do not require transfusion as per protocol specified guidelines
• Change in FACIT Fatigue scores over time
• Change in EORTC-QLQ-C30 scores over time
• Change in safety laboratory parameters over time
• TEAEs leading to discontinuation

•Cambio en los valores de la hemoglobina (Hgb) a lo largo del tiempo
•Cambio en la cifra absoluta de reticulocitos a lo largo del tiempo
•Cambio en la lactato-deshidrogenasa (LDH) a lo largo del tiempo
•Proporción de pacientes con LDH ≤1,5 × límite superior de la normalidad (LSN) a lo largo del tiempo
•Proporción de pacientes con ausencia de transfusión (AT), definida como los pacientes que no han recibido una transfusión y no la necesitan según las directrices indicadas en el protocolo.
•Cambio en las puntuaciones de FACIT-Cansancio a lo largo del tiempo
•Cambio en las puntuaciones de EORTC-QLQ-C30 a lo largo del tiempo
•Cambio en los parámetros analíticos de seguridad a lo largo del tiempo
•AAST que provoquen la interrupción

E.5.2.1

Timepoint(s) of evaluation of this end point

Over time throughout the study. Planned time points for all safety assessments are provided in the SoA (Section 1.3 of the protocol)

Con el tiempo a lo largo del estudio. Los puntos de tiempo planificados para todas las evaluaciones de seguridad se proporcionan en el SoA (Sección 1.3 del protocolo)

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

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)

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

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

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

algunos pacientes pueden recibir placebo al principio para mantener el cegamiento de la dosis

some patients rolling over may receive placebo at the beginning to maintain the dose blinding

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

Argentina

Brazil

Canada

Israel

Japan

Korea, Republic of

Malaysia

Taiwan

Thailand

United States

France

Poland

Netherlands

Spain

Czechia

Germany

Greece

Italy

Turkey

United Kingdom

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

LVLS

Última visita del último paciente.

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

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)

The protocol does not define any post-study treatment plan. Patients can continue their C5 inhibitor-based therapy based on investigator's decision. Patients completing the study may receive commercial danicopan once available in their country.

El protocolo no define ningún plan de tratamiento posterior al estudio. Los pacientes pueden continuar con su terapia basada en inhibidores de C5 según la decisión del investigador. Los pacientes que completen el estudio pueden recibir danicopan comercial una vez que esté disponible en su país.

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

2022-07-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-06-17

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

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