Clinical Trials Register

Summary
EudraCT Number:	2016-004578-16
Sponsor's Protocol Code Number:	VAL-1221-201-16
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-03-29
Trial results	View 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

UK - MHRA

A.2

EudraCT number

2016-004578-16

A.3

Full title of the trial

A Three-month, Open-Label, Randomized, Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of VAL-1221 versus Myozyme®/Lumizyme® in Patients with Late-Onset GSD-II (Pompe Disease) Followed by Open-Label Treatment with VAL-1221 in all Patients

A.3.1

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

A Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of VAL-1221 in Ambulatory and Ventilator-free Patients with Pompe Disease

A.4.1

Sponsor's protocol code number

VAL-1221-201-16

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	Valerion Therapeutics, LLC
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	Valerion Therapeutics, LLC
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	Voisin Consulting
B.5.2	Functional name of contact point	Clinical Trial Operations
B.5.3	Address:
B.5.3.1	Street Address	64 avenue Pierre Grenier
B.5.3.2	Town/ city	Boulogne-Billancourt
B.5.3.3	Post code	92100
B.5.3.4	Country	France
B.5.6	E-mail	clinicaltrialinformation@voisinconsulting.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.3.1	Product name	VAL-1221
D.3.2	Product code	VAL-1221
D.3.4	Pharmaceutical form	Solution for injection/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	VAL-1221
D.3.9.2	Current sponsor code	VAL-1221
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10.0
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Myozyme
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe 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	EU/3/00/018
D.3 Description of the IMP
D.3.1	Product name	Myozyme
D.3.4	Pharmaceutical form	Powder for concentrate for solution for injection/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	ALGLUCOSIDASE ALFA
D.3.9.1	CAS number	420784-05-0
D.3.9.3	Other descriptive name	rhGAA
D.3.9.4	EV Substance Code	SUB21275
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	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

Late-Onset GSD-II (Pompe Disease)

E.1.1.1

Medical condition in easily understood language

Pompe disease

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

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	10036143
E.1.2	Term	Pompe's disease
E.1.2	System Organ Class	100000004850

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045253
E.1.2	Term	Type II glycogen storage disease
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

Part 1:
• To assess the safety, tolerability and immunogenicity of VAL-1221 given IV

Part 2:
• To assess the long-term safety, tolerability and immunogenicity of VAL-1221 given IV

E.2.2

Secondary objectives of the trial

Part 1:
• To assess the pharmacokinetics of VAL-1221 given IV
• To assess the pharmacodynamics of VAL-1221 given IV

Part 2:
• To assess the long-term pharmacodynamics of VAL-1221 given IV
• To optimize dosing of VAL-1221 given IV

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patients ≥18 years
2. Patient is able and willing to provide informed consent prior to any study procedures are performed
3. Diagnosis of Glycogen Storage Disease II (GSD-II) based on one of the following:
a. Endogenous cultured skin fibroblast acid alpha glucosidase (GAA) activity <40% of adult normal level
b. Endogenous whole blood or dried blood spot GAA activity in deficiency range
c. Genetic analysis showing pathogenic variants in both alleles
4. Onset of Pompe disease-related symptoms after 1 year of age
5. Previously treated with Myozyme or Lumizyme for at least 12 months and on a stable regimen for the past 6 months
6. Sexually active patients willing to use an acceptable method of contraception (abstinence (defined as refraining from heterosexual intercourse during the entire period of the study and is the preferred and usual lifestyle of the patient), oral contraceptives, barrier method with spermicide, surgical sterilization, implanted or injectable contraceptives [including intrauterine devices with or without hormone release systems]) with a stable dose or insertion, as applicable, at least 1 month prior to Baseline, during the study and for 30 days after completion of treatment
a. If patient is female and not considered to be of childbearing potential, she is at least 2 years post-menopause, or has undergone a tubal ligation, a total hysterectomy or bilateral oophorectomy
b. If patient is female and of childbearing potential, she has a negative serum pregnancy test during screening and baseline and must be willing to undergo pregnancy testing at specific intervals during the study
7. Patient meets at least one of the following criteria:
a. >30% and <80% predicted upright forced volume capacity (FVC)
b. Able to walk >20% but <80% predicted normal on 6-minute walk test (6MWT) with or without use of assistive devices
8. Patient is willing and able to comply with protocol requirements

E.4

Principal exclusion criteria

1. Cardiac involvement in first year of life
2. Anti-GAA antibody titers >1:51,200 at two time points
3. Prior use of chaperone therapy for GSD-II within the last 12 months
4. Use of immunosuppressive medication other than glucocorticoids within 6 months prior to study enrollment
5. Use of invasive ventilatory assistance other than BiPAP at night or during periods of rest
6. Has received any investigational medication or has enrolled in any study involving investigational drugs or therapies within 30 days prior to first dose of study drug
7. Start of or change in usual regimen of albuterol or respiratory muscle training within 30 days prior to first dose of study drug
8. History of sensitivity to any of the constituents of the study drug
9. Patient is planning to become pregnant or to breastfeed during the study or is currently breastfeeding
10. Patient has a medical condition or circumstance that, in the opinion of the investigator, might compromise the patient’s ability to comply with the protocol or the patient’s well-being or safety
11. Patient has any condition that, in the view of the investigator, places the patient at high risk of poor treatment compliance or of not completing the study

E.5 End points

E.5.1

Primary end point(s)

Number of patients with adverse events, infusion-associated reactions to VAL-1221 and changes in anti-VAL-1221 antibody titers. Antibodies will be assessed for neutralizing capacity.

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the study

E.5.2

Secondary end point(s)

Part 1:
• Pharmacokinetic profile of VAL-1221 using plasma GAA activity and/or plasma GAA concentration.
• Change from Baseline to Week 12 in the presence and activity of GAA on muscle biopsy
• Change from Baseline to Week 12 in the amount of glycogen on muscle biopsy determined biochemically and histologically
• Change from Baseline to Week 12 in urinary hex4 excretion and serum creatine kinase

Part 2:
• Change from Baseline in Part 1 of the study to Months 12, 24 and 36
- Urinary hex4 excretion and creatinine
- Serum creatine kinase (CK)

E.5.2.1

Timepoint(s) of evaluation of this end point

Part 1:
• Up to week 12

Part 2:
• At Months 12, 24 and 36

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

Tolerability, immunogenicity

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

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

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

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

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)

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)

All patients who complete the study, including those maintained on rhGAA, will be offered inclusion in a further extension study pending review of safety data by the DSMB and review and approval of the extension study by relevant authorities and ethics committees.

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

2017-05-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-19

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-03-25

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