Clinical Trials Register

Summary
EudraCT Number:	2020-003467-26
Sponsor's Protocol Code Number:	NN7769-4516
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:	2022-01-20
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

2020-003467-26

A.3

Full title of the trial

Safety, efficacy and exposure of subcutaneously administered NNC0365-3769
(Mim8) prophylaxis in children with haemophilia A with or without FVIII
inhibitors

Seguridad, eficacia y exposición de la profilaxis con NNC0365-3769 (Mim8) administrado por vía subcutánea a niños con hemofilia A con o sin inhibidores del FVIII.

A.3.1

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

A research study investigating Mim8 in children with haemophilia A with or without inhibitors

Estudio de investigación de Mim8 en niños con hemofilia A con o sin inhibidores

A.4.1

Sponsor's protocol code number

NN7769-4516

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1255-1540

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/450/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novo Nordisk A/S
B.1.3.4	Country	Denmark
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	Novo Nordisk A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novo Nordisk A/S
B.5.2	Functional name of contact point	Clinical Transparency (1452)
B.5.3	Address:
B.5.3.1	Street Address	Novo Allé
B.5.3.2	Town/ city	Bagsværd
B.5.3.3	Post code	2880
B.5.3.4	Country	Denmark
B.5.6	E-mail	clinicaltrials@novonordisk.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	NNC0365-3769 A
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous 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	MASKED
D.3.9.3	Other descriptive name	NNC0365-3769
D.3.9.4	EV Substance Code	SUB198393
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	10 to 100
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

Haemophilia A

Haemophilia A with inhibitors

Hemofilia A,

Hemofilia A con inhibidores

E.1.1.1

Medical condition in easily understood language

Bleeding disorder, inherited deficiency in clotting factor VIII

Bleeding disorder, inherited deficiency in clotting factor VIII with antibodies to clotting factor replacement therapy

Desorden coagulación, deficiencia hereditaria factor VIII coagulación
Desorden coagulación, deficiencia hereditaria factor VIII coagulación con anticuerpos frente a terapia reemplazo factores coag

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10018938
E.1.2	Term	Haemophilia A (Factor VIII)
E.1.2	System Organ Class	100000004850

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10053751
E.1.2	Term	Hemophilia A with anti factor VIII
E.1.2	System Organ Class	100000004850

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 investigate the safety of Mim8 prophylaxis in children with haemophilia A with or without
FVIII inhibitors.

Investigar la seguridad de la profilaxis con Mim8 en niños con hemofilia A con o sin inhibidores del FVIII

E.2.2

Secondary objectives of the trial

Investigate the efficacy of Mim8 prophylaxis in children with haemophilia A with or without FVIII inhibitors.
Evaluate the consumption of coagulation factor replacement product per bleed treatment (number of injections) with Mim8 prophylaxis in children with haemophilia A with or without FVIII inhibitors.
Evaluate the development of anti-Mim8 antibodies with Mim8 prophylaxis in children with haemophilia A with or without FVIII inhibitors.
Investigate exposure of Mim8 after once-weekly and once-monthly subcutaneous dosing in children with haemophilia A with or without FVIII inhibitors.
Evaluate treatment burden with Mim8 prophylaxis in children with haemophilia A with or without FVIII inhibitors, as reported by their caregivers.
Investigate treatment preference among caregivers of previously treated children with haemophilia A with or without FVIII inhibitors.
Evaluate aspects of physical functioning with Mim8 prophylaxis in children with haemophilia A with or without FVIII inhibitors.

- Investigar eficacia de profilax con Mim8 en niños con hemofilia A con/sin inhibidores del FVIII
- Evaluar utilización de productos de reposición de factores de coagulación para el tto de hemorragias (nº inyecciones) en niños con hemofilia A con/sin inhibidores del FVIII en profilax con Mim8
- Evaluar desarrollo de anticuerpos frente a Mim8 en niños con hemofilia A con/sin inhibidores del FVIII en profilax con Mim8
- Investigar exposición a Mim8 después de la administración subcutánea una vez a la semana y una vez al mes en niños con hemofilia A con/sin inhibidores del FVIII
- Evaluar molestias derivadas del tto en niños con hemofilia A con o sin inhibidores del FVIII en profilax con Mim8, en base a lo comunicado por sus cuidadores
- Investigar preferencia de tto entre cuidadores de niños con hemofilia A tratados previamente con/sin inhibidores del FVIII
- Evaluar aspectos del funcionamiento físico en niños con hemofilia A con/sin inhibidores del FVIII en profilax con Mim8

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent obtained before any study-related activities. Study-related activities are any
procedures that are carried out as part of the study, including activities to determine suitability for the study.
2. Male and female participants with the diagnosis of congenital haemophilia A of any severity
based on medical records.
3. Aged 1−11 years (both inclusive) at the time of signing informed consent.
4. For previously treated participants :
a. Participant has been prescribed treatment with FVIII concentrate or bypassing agent in the last 26 weeks prior to screening.
b. Participants with endogenous FVIII activity above or equal to 1%, based on medical records, must have at least 1 treated bleed during the previous 26 weeks before screening for which factor VIII concentrate or bypassing agent has been prescribed (No requirements for participants with FVIII activity below 1%).
5. For previously untreated participants:
a. Diagnosis of severe haemophilia A (endogenous FVIII activity below 1%) based on medical records.
6. Child and parent/caregiver willingness and ability to comply with scheduled visits and study procedures, including the completion of diary and patient-reported outcomes questionnaires.

1. Obtención del consentimiento informado antes de cualquier actividad relacionada con el estudio. Se consideran actividades relacionadas con el estudio todos los procedimientos que se lleven a cabo como parte del estudio, incluidas las actividades para determinar la idoneidad para el mismo.
2. Varones o mujeres con diagnóstico de hemofilia A congénita de cualquier gravedad según la historia clínica.
3. Edad comprendida entre 1 y 11 años (ambos inclusive) en el momento de firmar el consentimiento informado.
4. En los participantes tratados previamente:
a. Al participante se le ha prescrito tratamiento con concentrado de FVIII o un agente bypass en las 26 semanas previas a la selección.
b. Los participantes con una actividad del FVIII endógeno mayor o igual al 1 %, según la historia clínica, deben tener al menos una hemorragia tratada en las 26 semanas previas a la selección para la que se haya prescrito concentrado de factor VIII o un agente bypass (sin requisitos para los participantes con una actividad del FVIII menor del 1 %).
5. En los participantes no tratados previamente:
c. Diagnóstico de hemofilia A grave (actividad del factor VIII endógeno menor del 1 %) según la historia clínica.
6. Disposición y capacidad del niño y los padres o el cuidador para cumplir las visitas programadas y los procedimientos del estudio, incluida la cumplimentación del diario y de cuestionarios de resultados comunicados por los pacientes.

E.4

Principal exclusion criteria

1. Known or suspected hypersensitivity to study product or related products.
2. Previous participation in this study. Participation is defined as signed informed consent.
3. Exposure to non-factor haemostatic products for bleeding prophylaxis within 6 months (or 5 half-lives of the medicinal product, whichever is shorter) prior to planned first dose, for participants not included in the run-in.
4. Known congenital or acquired coagulation disorders other than haemophilia A.
5. Other conditions (e.g. autoimmune disease) or laboratory abnormality that may increase risk of
bleeding or thrombosis, as evaluated by the investigator.
6. Any disorder, except for conditions associated with haemophilia A, that in the investigator’s
opinion might jeopardise the participant’s safety or compliance with the protocol.
7. Mental incapacity, unwillingness to cooperate or a language barrier precluding adequate
understanding and cooperation.
8. Lack of adequate parental/caregiver support to enter accurately and timely information
regarding treatment and bleeding episodes into an (electronic) diary.
9. Previous or current treatment for thromboembolic disease (with the exception of previous
catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or
signs of thromboembolic disease.
10. Major surgery planned to take place after screening.
11. Immune tolerance induction planned to take place after treatment initiation.
12. Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine
aminotransferase (ALT) above 3 times the upper limit of normal combined with total bilirubin above 1.5 times the upper limit of normal measured at screening.
13. Serum creatinine above 1.5 x upper limit of normal (ULN), measured at screening.
14. Pregnancy (female participants).

1. Hipersensibilidad conocida o sospechada a los productos del estudio o a productos relacionados.
2. Participación previa en este estudio. La participación se define como la firma del consentimiento informado.
3. Exposición a productos hemostáticos que no sean factores para la profilaxis de hemorragias en los 6 meses (o 5 semividas del medicamento, lo que sea más corto) previos a la primera dosis prevista, para participantes no incluidos en el periodo de pre-inclusión.
4. Trastornos congénitos o adquiridos conocidos de la coagulación distintos de la hemofilia A.
5. Otras enfermedades (p. ej., enfermedad autoinmunitaria) o anomalías analíticas que puedan aumentar el riesgo de hemorragia o trombosis, según la evaluación del investigadora.
6. Cualquier trastorno, excepto los procesos asociados a la hemofilia A, que en opinión del investigador podría poner en peligro la seguridad del participante o el cumplimiento del protocolo.
7. Incapacidad mental, falta de cooperación o barrera idiomática que impida la debida comprensión y colaboración.
8. Falta de apoyo por parte de los padres o el cuidador para registrar información exacta y en el momento requerido sobre el tratamiento y los episodios hemorrágicos en un diario (electrónico)
9. Tratamiento previo o actual por enfermedad tromboembólica (con la excepción de trombosis previa asociada a un catéter para la que no esté recibiendo tratamiento antitrombótico) o signos de enfermedad tromboembólica.
10. Intervención de cirugía mayor prevista después de la selección.
11. Inducción de inmunotolerancia prevista después del inicio del tratamiento.
12. Disfunción hepática definida como un valor de aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) por encima de 3 veces el límite superior de la normalidad combinado con un valor de bilirrubina total por encima de 1,5 veces el límite superior de la normalidad medido en la selección.
13. Creatinina sérica por encima de 1,5 veces el límite superior de la normalidad (LSN), medida en la selección.
14. Embarazo (mujeres participantes)

E.5 End points

E.5.1

Primary end point(s)

1. Number of treatment emergent adverse events

1. Número de acontecimientos adversos de aparición durante el tratamiento

E.5.1.1

Timepoint(s) of evaluation of this end point

1. From treatment initiation to follow up visit (week 0 to week 72)

1- Desde el inicio del tratamiento hasta la visita de seguimiento (de la semana 0 a la semana 72)

E.5.2

Secondary end point(s)

1. Number of treated bleeds
2. Number of treated spontaneous bleeds
3. Number of treated traumatic bleeds
4. Number of treated joint bleeds
5. Number of treated target joint bleeds
6. Number of injection site reactions
7. Consumption of factor product per bleed treatment
8. Occurrence of anti-Mim8 antibodies
9. Mim8 plasma concentration
10. Change in physical function domain of Paediatric Quality of Life inventory (PEDS-QL) Generic Core Scales
11. Treatment preference for Mim8 versus previous treatment using Caregiver Haemophilia Patient Preference Questionnaire (Caregiver H-PPQ)
12. Change in participants’ treatment burden using the Haemophilia treatment experience measure (Hemo TEM)

1. Número de hemorragias tratadas
2. Número de hemorragias espontâneas tratadas
3. Número de hemorragias traumáticas tratadas
4. Número de hemorragias articulares tratadas
5. Número de hemorragias en articulaciones diana tratadas
6. Número de reacciones en el lugar de inyección
7. Utilización de productos con factor para el tratamiento de las hemorragias
8. Aparición de anticuerpos frente a Mim8
9. Concentración plasmática de Mim8
10. Variación del módulo de función física de las escalas básicas genéricas del cuestionario de calidad de vida pediátrica (PEDS-QL)
11. Preferencia por Mim8 en comparación con el tratamiento previo mediante el cuestionario H PPQ del cuidador
12. Variación de las molestias al paciente derivadas del tratamiento mediante el cuestionario de medida de la experiencia del tratamiento de la hemofilia (Hemo-TEM)

E.5.2.1

Timepoint(s) of evaluation of this end point

1-6 . From treatment initiation to end of treatment (week 0 to week 52)
7. From run-in initiation to end of treatment (week -26 to week 52)
8-10. From treatment initiation to end of treatment (week 0 to week 52)
11. Once during treatment (week 26)
12. From treatment initiation to end of treatment (week 0 to week 52)

1-6. Desde el inicio del tratamiento hasta el final del tratamiento (de la semana 0 a la semana 52)
7. Desde el inicio del periodo de pre-inclusion hasta el final de tratamiento (de la semana -26 a la semana 52)
8-10. Desde el inicio del tratamiento hasta el final del tratamiento (de la semana 0 a la semana 52)
11. Una vez durante el tratamiento (semana 26)
12. Desde el inicio del tratamiento hasta el final del tratamiento (de la semana 0 a la semana 52)

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.3

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

China

European Union

India

Israel

Japan

Korea, Republic of

Russian Federation

Switzerland

Taiwan

United Kingdom

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

UVUP

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

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)

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)

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

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)

none

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

2022-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-04-06

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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