Clinical Trials Register

Summary
EudraCT Number:	2020-004686-39
Sponsor's Protocol Code Number:	EFC14462
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2021-01-21
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

Germany - BfArM

A.2

EudraCT number

2020-004686-39

A.3

Full title of the trial

An Open-label, Multinational, Multicenter, Intravenous Infusion Study of the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of avalglucosidase alfa in Treatment naïve Pediatric Participants with
Infantile-Onset Pompe Disease (IOPD)

A.3.1

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

Clinical Study for Treatment-naïve IOPD Babies to Evaluate Efficacy and Safety of enzyme replacement therapy (ERT) With Avalglucosidase Alfa

A.3.2

Name or abbreviated title of the trial where available

Baby-COMET

A.4.1

Sponsor's protocol code number

EFC14462

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1246-6645

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/174/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi-Aventis Recherche & Développement
B.1.3.4	Country	France
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	Sanofi-Aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi-Aventis Deutschland GmbH
B.5.2	Functional name of contact point
B.5.3.4	Country	Germany
B.5.6	E-mail	medinfo.de@sanofi.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	Yes
D.2.1.1.1	Trade name	Nexviadyme
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	EMEA-001945-PIP01
D.3 Description of the IMP
D.3.1	Product name	Avalglucosidase Alfa
D.3.2	Product code	GZ402666
D.3.4	Pharmaceutical form	Powder for 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	avalglucosidase alfa
D.3.9.2	Current sponsor code	GZ402666
D.3.9.3	Other descriptive name	RECOMBINANT HUMAN Α-GLUCOSIDASE CONJUGATED WITH SYNTHETIC BISMANNOSE-6-PHOSPHATE-MAN6 GLYCAN
D.3.9.4	EV Substance Code	SUB120294
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	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

Glycogen storage disease type II

E.1.1.1

Medical condition in easily understood language

Glycogen storage disease type II

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	20.1
E.1.2	Level	PT
E.1.2	Classification code	10053185
E.1.2	Term	Glycogen storage disease type II
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic 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 determine the effect of avalglucosidase alfa treatment on survival and invasive ventilator-free survival of IOPD participants less than or equal to 6 months of age after 52 weeks of treatment.

E.2.2

Secondary objectives of the trial

- To determine the effect of avalglucosidase alfa treatment on survival and invasive ventilator-free survival at 12 and 18 months of age, as well as the change in left ventricular mass Z-score (LVM Z-score); Alberta Infant Motor Scale (AIMS) score; body length, body weight, and head circumference Z scores; and urinary Hex4 at Week 52 in IOPD
participants less than or equal to 6 months of age

- To determine safety, tolerability, and immunogenicity of avalglucosidase alfa

- To determine the PK profile at Week 12 and Week 52

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participants must have confirmed diagnosis of infantile-onset Pompe disease defined as: the presence of 2 lysosomal acid α-glucosidase (GAA) pathogenic variants and a documented GAA deficiency from blood, skin, or muscle tissue; or the presence of 1 GAA pathogenic variant and a documented GAA deficiency from blood, skin and muscle tissue in 2 separate samples (from either 2 different tissues or from the same tissue but at 2 different sampling dates).

- Participants must have established cross-reactive immunological material (CRIM) status available prior to enrollment.

- Participants must have cardiomyopathy at the time of diagnosis: ie, LVMI equivalent to mean age specific LVMI
+1 standard deviation for participants diagnosed by newborn screening or sibling screening;
+2 standard deviation for participants diagnosed by clinical evaluation.

- Parents or legally authorized representative(s) must be capable of giving signed informed consent

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
- Participants with symptoms of respiratory insufficiency, including any ventilation use (invasive or noninvasive) at the time of enrollment.
- Participants with major congenital abnormality.
- Participants with clinically significant organic disease (with the exception of symptoms relating to Pompe disease).
- Participant received any Pompe disease specific treatment, eg ERT gene therapy.
- Participant who has previously been treated in any clinical trial of avalglucosidase alfa.
- Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants who are alive and free of invasive ventilation at Week 52

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52

E.5.2

Secondary end point(s)

1/ Proportion of participants who are alive and free of invasive ventilation at 12 and 18 months of age

2/ Proportion of participants who are alive at Week 52

3/ Proportion of participants who are alive at 12 and 18 months of age

4/ 4/ Proportion of participants who are free of ventilator use (invasive and non-invasive separate and combined) at Week 52

5/ Proportion of participants who are free of supplemental oxygen use at Week 52

6/ Change from baseline to Week 52 in LVM-Z score

7/ Change from baseline to Week 52 in AIMS score

8/ Change from baseline to Week 52 in body length Z-scores

9/ Change from baseline to Week 52 in body weight Z-scores

10/ Change from baseline to Week 52 in head circumference Z-scores

11/ Change from baseline to Week 52 in body length percentiles

12/ Change from baseline to Week 52 in body weight percentiles

13/ Change from baseline to Week 52 in head circumference percentiles

14/ Change from baseline to Week 52 in urinary Hex4

15/ Assessment of treatment-emergent adverse events (TEAE) including infusion-associated reactions (IAR)

16/ Physical examination

17/ Clinical laboratory evaluations

18/ Vital signs measurements

19/ 12-lead electrocardiogram (ECG)

20/ Immunogenicity assessments

21/ Plasma concentration of avalglucosidase alfaa

E.5.2.1

Timepoint(s) of evaluation of this end point

1/, 3/: at 12 and 18 months of age

2/ and from 4/ to 14/ : Week 52

15/: week 52, week 212

From 16/ to 20/: Week 52, Week 208

21/ : at Day 1, Week 12, and Week 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

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

China

United States

Belgium

France

Germany

Italy

Netherlands

Taiwan

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

LPLV

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)

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)

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

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)

No different plans from the expected normal treatment of the condition

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

2021-07-19

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

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