Clinical Trials Register

Summary
EudraCT Number:	2019-003829-18
Sponsor's Protocol Code Number:	ALXN2040-PNH-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:	2021-05-24
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

2019-003829-18

A.3

Full title of the trial

A Phase 3 Study of Danicopan (ALXN2040) as Add-on Therapy to a C5 Inhibitor (Eculizumab or Ravulizumab) in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH)

Studio di fase 3 su danicopan (ALXN2040) come terapia aggiuntiva a un inibitore C5 (Eculizumab o Ravulizumab) in pazienti affetti da emoglobinuria parossistica notturna che presentano emolisi extravascolare clinicamente evidente (EVH)

A.3.1

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

Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)

Danicopan come terapia aggiuntiva a un inibitore C5 in partecipanti affetti da emoglobinuria parossistica notturna (EPN) che presentano emolisi extravascolare clinicamente evidente (EVH)

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

ALXN2040-PNH-301

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04469465

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 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	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	147100615
B.5.5	Fax number	147100611
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 (ALXN2040)
D.3.2	Product code	[ACH-0144471]
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.3.9.1	CAS number	1903768-17-1
D.3.9.2	Current sponsor code	ACH-0144471
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	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.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 (ALXN2040)
D.3.2	Product code	[ACH-0144471]
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.3.9.1	CAS number	1903768-17-1
D.3.9.2	Current sponsor code	ACH-0144471
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	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
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 Who Have Clinically Evident Extravascular Hemolysis (EVH)

Pazienti affetti da emoglobinuria parossistica notturna che presentano emolisi extravascolare clinicamente evidente (EVH)

E.1.1.1

Medical condition in easily understood language

Patients with Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH)

Pazienti affetti da emoglobinuria parossistica notturna che presentano emolisi extravascolare clinicamente evidente (EVH)

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 evaluate the efficacy of danicopan as compared to placebo as add-on therapy to a C5 inhibitor at 12 weeks

Valutare l’efficacia di danicopan rispetto al placebo come terapia aggiuntiva a un inibitore C5 a 12 settimane

E.2.2

Secondary objectives of the trial

• Percentage Of Participants With Transfusion Avoidance
• Change From Baseline In Functional Assessment Of Chronic Illness Therapy (FACIT) Fatigue Scores
• Change From Baseline In Absolute Reticulocyte Count

• Percentuale di pazienti che presentano non ricorso alla trasfusione
• Variazione rispetto al basale nel punteggio Valutazione funzionale della terapia per le malattie croniche FACIT
• Variazione rispetto al basale nella conta assoluta dei reticolociti

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Diagnosis of PNH
• Clinically Evident EVH defined by:
- Anemia (Hgb =9.5 gram/deciliter) with absolute reticulocyte count =120 x 10^9/liter.
- At least 1 packed red blood cell or whole blood transfusion within 6 months prior to the start of the study.
• Receiving a C5 inhibitor for at least 6 months prior to Day 1
• Platelet count =30,000/microliters (µL)
• Absolute neutrophil counts =750/µL.
• Documentation of/or willingness to receive vaccinations and prophylactic antibiotics as required.

-Diagnosi di EPN
- Emolisi extravascolare (EVH) clinicamente evidente definita da:
- Anemia (Hgb =9,5 g/dl) con conta assoluta dei reticolociti =120 × 10 9 /l.
-Almeno 1 trasfusione di concentrati eritrocitari o di sangue intero nei 6 mesi precedenti l’inizio dello studio
-Ricezione di un inibitore C5 per almeno 6 mesi prima del Giorno 1
- Conta piastrinica =30.000/µl
- Conta assoluta dei neutrofili =750/µl
- Documentazione di vaccinazione contro la Neisseria meningitidis

E.4

Principal exclusion criteria

• History of a major organ transplant or hematopoietic stem cell transplantation (HSCT).
• Participants with known aplastic anemia or other bone marrow failure that requires HSCT or other therapies including anti-thymocyte globulin and/or immunosuppressants.
• Known or suspected complement deficiency.
• Laboratory abnormalities at screening, including:
- Alkaline phosphatase >2 x upper limit of normal (ULN).
- Alanine aminotransferase >2 x ULN.
- Direct bilirubin >2 x ULN (unless due to EVH or documented Gilbert’s Syndrome.
• Current evidence of biliary cholestasis.
• Estimated glomerular filtration rate <30 milliliters/minute/1.73 meter squared and/or are on dialysis.

• Anamnesi di trapianto di organi maggiori o trapianto di cellule staminali ematopoietiche (HSCT).
• Anemia aplastica nota o altra insufficienza midollare che richiede HSCT o altre terapie, comprese globulina antitimocitaria e/o immunosoppressori
• Deficit del complemento noto o sospetto.
Risultati di laboratorio anomali allo Screening, tra cui:
• Fosfatasi alcalina >2 × limite superiore della norma (ULN)
• Alanina aminotransferasi >2 x ULN
• Bilirubina diretta >2 × ULN (a meno che non sia dovuta a emolisi extravascolare, i pazienti con sindrome di Gilbert)
• Evidenza attuale di colestasi biliare.
• Velocità di filtrazione glomerulare stimata <30 ml/min/1,73 m 2 e/o in dialisi.

E.5 End points

E.5.1

Primary end point(s)

• Change From Baseline In Hemoglobin (Hgb)

Variazione dell’emoglobina (Hgb) rispetto al basale

E.5.1.1

Timepoint(s) of evaluation of this end point

At Week 12

Alla Settimana 12

E.5.2

Secondary end point(s)

• Percentuale di pazienti che presentano non ricorso alla trasfusione
• Variazione rispetto al basale nel punteggio FACIT
• Variazione rispetto al basale nella conta assoluta dei reticolociti

E.5.2.1

Timepoint(s) of evaluation of this end point

At Week 12

Alla Settimana 12

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Effect on biomarkers

Effetto sui biomercatori

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Brazil

Canada

Japan

Korea, Republic of

Malaysia

Taiwan

Thailand

United States

Austria

Denmark

Finland

France

Germany

Italy

Netherlands

Poland

Spain

Sweden

Switzerland

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

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

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.

Il protocollo non definisce alcun piano di trattamento post-studio. I pazienti possono continuare la terapia a base di inibitori C5 in base alla decisione dello sperimentatore.
I pazienti che completano lo studio possono ricevere danicopan commerciale una volta disponibile nel loro paese.

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

2020-10-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-11-03

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

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