Clinical Trials Register

Summary
EudraCT Number:	2019-003830-17
Sponsor's Protocol Code Number:	ACH228-110
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-07-14
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

2019-003830-17

A.3

Full title of the trial

A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of the Oral Factor D (FD) Inhibitor ALXN2050 (ACH-0145228) in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients as Monotherapy

Ensayo abierto fase 2 de prueba de concepto para evaluar la eficacia, seguridad y farmacocinética del inhibidor oral del factor D (FD) ALXN2050 (ACH 0145228) en pacientes con hemoglobinuria paroxística nocturna (HPN) como monoterapia.

A.3.1

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

Study of the Oral Factor D (FD) Inhibitor ALXN2050 (ACH-0145228) in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients as Monotherapy

Estudio del inhibidor oral del factor D (FD) ALXN2050 (ACH-0145228) en pacientes con hemoglobinuria paroxística nocturna (HPN) como monoterapia

A.3.2

Name or abbreviated title of the trial where available

Study of the Oral Factor D (FD) Inhibitor ALXN2050 in PNH Patients as Monotherapy

A.4.1

Sponsor's protocol code number

ACH228-110

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04170023

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1241-2441

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 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	+34 93 2723019
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/3/21/2401
D.3 Description of the IMP
D.3.1	Product name	ALXN2050
D.3.2	Product code	ALXN2050
D.3.4	Pharmaceutical form	Capsule
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	N/A
D.3.9.1	CAS number	2086178-00-7
D.3.9.2	Current sponsor code	ALXN2050
D.3.9.3	Other descriptive name	ACH-0145228
D.3.9.4	EV Substance Code	SUB204167
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	60
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

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)

Hemoglobinuria paroxística nocturna (HPN)

E.1.1.1

Medical condition in easily understood language

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Hemoglobinuria paroxística nocturna (HPN)

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 ALXN2050 based on improvement in hemoglobin (Hgb)

Evaluar la eficacia de ALXN2050 en función de la mejora de la hemoglobina (Hgb)

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of ALXN2050 based on reduction in transfusion requirements
• To evaluate the efficacy of ALXN2050 based on lactate dehydrogenase (LDH)
• To assess laboratory markers of hemolysis and other markers relevant in patients with paroxysmal nocturnal hemoglobinuria (PNH)

• Evaluar la eficacia de ALXN2050 en función de la reducción de las necesidades de transfusión
• Evaluar la eficacia de ALXN2050 en función de la lactato deshidrogenasa (LDH)
• Evaluar los marcadores analíticos de hemólisis y otros marcadores relevantes en pacientes con hemoglobinuria paroxística nocturna (HPN)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All patients must meet all of the following conditions:
1. Diagnosis of PNH.
2. Male or female, ≥ 18 years of age (or minimum adult age in accordance with local legal requirements).

Eligibility Criteria Specific for Group 1:
1. PNH Patients who have no history of treatment with any complement inhibitor at any dose.
2. PNH Type III erythrocyte or granulocyte clone size ≥10%
3. Absolute reticulocyte count ≥100×10^9/liter [L].
4. Anemia (Hgb <10.5 grams/deciliter [g/dL]).
5. LDH ≥1.5× upper limit of normal.
6. Platelet count ≥30,000/microliter (µL) without the need for platelet transfusions.
7. Absolute neutrophil count (ANC) ≥750/ µL.

Eligibility Criteria Specific for Group 2:
Patients on stable eculizumab switching to ALXN2050 (Group 2) must meet the following criteria:
1. Stable background regimen of at least 24 weeks for eculizumab without change in dose or interval for at least the past 8 weeks
2. Anemia (Hgb <10 g/dL)
3. Absolute reticulocyte count ≥100×10^9/L
4. Platelet count ≥30,000/µL without the need for platelet transfusions
5. Absolute neurophil count (ANC) ≥750/ µL

Eligibility Criteria Specific for Group 3:
1. Patient received danicopan during Study ACH-471-103.

Todos los pacientes deben cumplir todas las condiciones siguientes:
1. Diagnóstico de HPN.
2. Hombre o mujer, ≥18 años de edad (o edad adulta mínima de acuerdo con los requisitos legales locales).
Criterios de elegibilidad específicos para el grupo 1:
1. Pacientes con HPN que no tienen antecedentes de tratamiento con ningún inhibidor del complemento a ninguna dosis.
2. Tamaño del clon de granulocitos o eritrocitos tipo III de HPN ≥10 %
3. Recuento absoluto de reticulocitos ≥100×10^9/litro [l].
4. Anemia (Hgb <10,5 gramos/decilitro [g/dl]).
5. ≥1,5 x LSN (límite superior de la normalidad).
6. Recuento plaquetario ≥30 000/microlitro (μl) sin necesidad de transfusiones de plaquetas.
7. Cifra absoluta de neutrófilos (ANC) ≥750/μL.

Criterios de elegibilidad específicos para el grupo 2:
Los pacientes con eculizumab estable que cambien a ALXN2050 (grupo 2) deben cumplir los siguientes criterios:
1. Régimen de base estable de al menos 24 semanas para eculizumab sin cambio en la dosis o el intervalo durante al menos las últimas 8 semanas
2. Anemia (Hgb <10 g/dl)
3. Recuento absoluto de reticulocitos ≥100×10^9/l
4. Recuento plaquetario ≥30 000/μl sin necesidad de transfusiones de plaquetas 5. Cifra absoluta de neutrófilos (ANC) ≥750/ μL
Criterios de elegibilidad específicos para el grupo 3:
1. El paciente recibió danicopán durante el estudio ACH-471-103.

E.4

Principal exclusion criteria

1. History of a major organ transplant or hematopoietic stem cell/marrow transplant .
2. Known aplastic anemia or other bone marrow failure that requires HSCT, or if these patients are on immunosuppressive agents such as (but not limited to) cyclosporine, tacrolimus, mycophenolate, or others for less than 24 weeks prior to enrollment.
3. Known underlying bleeding disorders (eg, coagulation factor deficiencies, idiopathic thrombocytopenic purpura, Von Willebrand disease) or any other conditions leading to anemia not primarily associated with PNH.
4. Estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared and/or are on dialysis.

1. Antecedentes de trasplante de órganos importantes o trasplante de células madre hematopoyéticas/médula ósea.
2. Anemia aplásica conocida u otra insuficiencia de la médula ósea que requiera TCMH, o si estos pacientes están recibiendo inmunodepresores como (entre otros) ciclosporina, tacrolimus, micofenolato u otros durante menos de 24 semanas antes de la inscripción.
3. Trastornos hemorrágicos subyacentes conocidos (p. ej., deficiencias del factor de coagulación, púrpura trombocitopénica idiopática, enfermedad de Von Willebrand) o cualquier otra afección que lleve a anemia no asociada principalmente a la HPN.
4. Tasa de filtración glomerular estimada <30 mililitros/minuto/1,73 metros cuadrados y/o están en diálisis.

E.5 End points

E.5.1

Primary end point(s)

1. Change in Hgb relative to baseline

1. Cambio en la Hgb en relación con el valor inicial

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Week 12

1. Semana 12

E.5.2

Secondary end point(s)

2. Number Of Patients Who Have Transfusion Avoidance
3. Number Of RBC Units Transfused and Transfusion Instances
Transfusion requirements during the 12 weeks of treatment will be compared to 12 weeks of historical transfusion requirements.
4. Change In LDH Relative to Baseline
5. Change From Baseline In Absolute Reticulocyte Count
6. Change From Baseline In Direct Bilirubin
7. Change From Baseline In Total Bilirubin
8. Change From Baseline In PNH RBC Clone Size
9. Change From Baseline In C3 Complement Protein Fragment Deposition On PNH RBCs
10. Incidence of TEAEs, SAEs, and Events Leading To Discontinuation Of Study Medication
11. Change in HgB Relative To Baseline
12. Change in LDH Relative To Baseline
13. Change in FACIT Fatigue Scale (Version 4) Scores Relative To Baseline

2. Número de pacientes con ahorro de transfusiones
3. Número de unidades de eritrocitos Transfundidas e Instancias de transfusión Las necesidades de transfusión durante las 12 semanas de tratamiento se compararán con las 12 semanas de necesidades de transfusión históricas.
4. Cambio en la LDH con respecto al inicio
5. Cambio desde el inicio en el recuento absoluto de reticulocitos
6. Cambio desde el inicio en la bilirrubina directa
7. Cambio con respecto al inicio en la bilirrubina total
8. Cambio desde el inicio en el tamaño del clon de eritrocitos de HPN
9. Cambio desde el inicio en el fragmento de proteína del complemento C3
Depósito en los eritrocitos de HPN
10. Incidencia de AAST, AAG y acontecimientos que provocaron la interrupción del medicamento del estudio
11. Cambio en HgB con respecto al inicio
12. Cambio en la LDH con respecto al inicio
13. Cambio en las puntuaciones de la escala de fatiga FACIT (versión 4) en relación con el inicio

E.5.2.1

Timepoint(s) of evaluation of this end point

2 - 3: Up to Week 12
4 - 9: Week 12
10: Through Study Completion, An Average Of 121 Weeks
11 - 12: Long-term Extension Period, Week 16 to Week 108
13: Week 12, Week 108

2 - 3: Hasta la semana 12
4 - 9: Semana 12
10: Hasta la finalización del estudio, una media de 121 semanas
11 - 12: Período de extensión a largo plazo, de la semana 16 a la semana 108
13: Semana 12, Semana 108

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

Yes

E.6.10

Pharmacogenetic

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

Efecto en los biomarcadores

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

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

Canada

Korea, Republic of

New Zealand

Turkey

France

Germany

Italy

Spain

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

The end of the study is defined as the date of the last visit of the last patient remaining in the study.

El final del estudio se define como la fecha de la última visita del último paciente que queda en el estudio.

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