ICH GCP - EU Clinical trials Registry - 2019-002936-97 (FR)

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Summary
EudraCT Number:	2019-002936-97
Sponsor's Protocol Code Number:	LTFU-ABO-101
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-02-09
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

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2019-002936-97

A.3

Full title of the trial

A Long-term Follow-up Study of Patients with MPS IIIB from Gene Therapy Clinical Trials Involving the Administration of ABO-101 (rAAV9.CMV.hNAGLU)

Étude de suivi à long terme des patients atteints de MPS IIIB ayant participé aux essais cliniques de thérapie génique impliquant l’administration d’ABO-101 (rAAV9.CMV.hNAGLU)

A.3.1

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

A Long-term Follow-up Study of Patients with MPS IIIB from Gene Therapy Clinical Trials Involving the Administration of ABO-101 (rAAV9.CMV.hNAGLU)

Étude de suivi à long terme des patients atteints de MPS IIIB ayant participé aux essais cliniques de thérapie génique impliquant l’administration d’ABO-101 (rAAV9.CMV.hNAGLU)

A.4.1

Sponsor's protocol code number

LTFU-ABO-101

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04655911

A.5.4

Other Identifiers

Name:

IND Number

Number:

16671

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	Abeona Therapeutics Europe SL.
B.1.3.4	Country	Spain
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	Abeona Therapeutics 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	Abeona Therapeutics Inc
B.5.2	Functional name of contact point	Head of European Medical Affairs
B.5.3	Address:
B.5.3.1	Street Address	Avenida de Manoteras 30, A207-208
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28050
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34689166070
B.5.5	Fax number	+34911726254
B.5.6	E-mail	sanfilippo@abeonatherapeutics.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/3/16/1825
D.3 Description of the IMP
D.3.1	Product name	rAAV9.CMV.hNAGLU
D.3.2	Product code	ABO-101
D.3.4	Pharmaceutical form	Suspension for injection
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	rAAV9.CMV.hNAGLU
D.3.9.2	Current sponsor code	ABO-101
D.3.9.3	Other descriptive name	Adeno-associated viral vector serotype 9 containing the human N-acetyl-alpha-glucosaminidase gene
D.3.9.4	EV Substance Code	SUB195018
D.3.10	Strength
D.3.10.1	Concentration unit	vector genomes (vg)/mL
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	150000000000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
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

MPS IIIB is a devastating lysosomal storage disease, caused by a N-α-acetylglucosaminidase (NAGLU) gene defect. Infants with MPS IIIB appear normal at birth, but the disease is relentlessly progressive, with deterioration of social and adaptive abilities, neurocognitive decline, and premature death. Death typically occurs by end of the second or beginning of the third decade. Quite importantly, there is no treatment currently available for the disease.

E.1.1.1

Medical condition in easily understood language

Mucopolysaccharidosis type IIIB is a genetic disease in children, caused by the toxicity of an accumulation of substances in the body that generate a progressive deterioration.

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	10056890
E.1.2	Term	Mucopolysaccharidosis III
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

The primary objective of the study is to evaluate the long-term safety/tolerability of ABO-101 in patients with MPS IIIB.

E.2.2

Secondary objectives of the trial

The secondary objective is to evaluate the neurocognitive evolution of patients with MPS IIIB treated with ABO-101.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Participants that have completed a prior clinical trial involving the administration of ABO-101.
• Parent(s)/legal guardian(s) of participant willing and able to complete the informed consent process and comply with study procedures and visit schedule.

E.4

Principal exclusion criteria

• Planned or current participation in another clinical trial that may confound the safety or efficacy evaluation of ABO-101 during this study.
• Any other situation that precludes the participant from undergoing procedures required in this study.

E.5 End points

E.5.1

Primary end point(s)

Long-term product safety as defined by the incidence, type, and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety will be evaluated along the entire trial for 3 years.

E.5.2

Secondary end point(s)

• Neurocognitive evolution based on Age Equivalent assessments included in the prior clinical trial including:
- Change from baseline (in prior trial) in the Age Equivalent and Developmental Quotient (DQ) after treatment compared to Natural History Study data calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children; Second Edition, based on chronological and developmental age [Time frame: Month 30, 36, 42, 48, 60]
- Change from baseline (in prior trial) in the Cognitive Age Equivalent and Developmental Quotient after treatment compared to Natural History Study, calculated using the Bayley Scales of Infant and Toddler Development – Third edition or the Kaufman Assessment Battery for Children. Second Edition, based on developmental age [Time Frame: Month 30, 36, 42, 48, 60]
- Change from baseline(in prior trial) in the Adaptive Age Equivalent score after treatment compared to Natural History Study data, as assessed by parent report using the Vineland Adaptive Behavior Scale II Survey form [Time frame: Month 30, 36, 42, 48, 60]
• Quality of life based on Pediatric Quality of Life Inventory (PedsQL™ and PedsQL Grastrointestinal Symptom scales-this last one, only applicable for participants who completed these evaluations in the prior clinical trial), Parenting Stress Index, 4th Edition (PSI-4).
• Evolution on Parental Global Impression Score, Clinical Global Impression Improvement Score and Parent Symptom Score Questionnaire.
• Long-term immunological responses defined as antibody formation (humoral) and T-cell responses (cellular) against the AAV9 capsid and against the α-N-acetylglucosaminidase (NAGLU) transgene product.
• Long-term viral load, in applicable cases.

E.5.2.1

Timepoint(s) of evaluation of this end point

Annually (± 2 months) for three years.

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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Long Term Follow Up

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

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

Yes

E.8.1.7.1

Other trial design description

Long Term Follow Up

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

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

France

Germany

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

The end of the clinical trial is defined as the Last Participant Last Visit.

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

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)

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

These children have severe cognitive problems making them very difficult to understand an explanation about the study and also to sign the informed consent. Based on a expert opinion, unique ICF for parents or legal representatives is proposed.

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)

This is the 3 years follow up study after the participation in previous study where IMP was administered to subject. No additional studies are planned.

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

2021-07-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-01

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

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