Clinical Trials Register

Summary
EudraCT Number:	2020-003678-28
Sponsor's Protocol Code Number:	AVXS-101-CL-102
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-09-15
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2020-003678-28

A.3

Full title of the trial

Phase I, Open-Label, Dose Comparison Study of AVXS-101 for Sitting but Non-
Ambulatory Patients with Spinal Muscular Atrophy

A.3.1

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

Single Dose Gene Replacement Therapy Clinical Trial for Patients with
Spinal Muscular Atrophy

A.4.1

Sponsor's protocol code number

AVXS-101-CL-102

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/315/2019

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AveXis, 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	AveXis, 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	AveXis, Inc
B.5.2	Functional name of contact point	Clinical Trial Operations Manager
B.5.3	Address:
B.5.3.1	Street Address	2275 Half Day Road,
B.5.3.2	Town/ city	Bannockburn, IL
B.5.3.3	Post code	60015
B.5.3.4	Country	United States
B.5.4	Telephone number	+353 (1) 556-2364
B.5.6	E-mail	medinfo.emea@avexis.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	Zolgensma
D.2.1.1.2	Name of the Marketing Authorisation holder	AveXis, Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
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/3/15/1509
D.3 Description of the IMP
D.3.1	Product name	AVXS-101
D.3.2	Product code	AVXS-101
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intrathecal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ONASEMNOGENE ABEPARVOVEC
D.3.9.1	CAS number	1922968-73-7
D.3.9.2	Current sponsor code	AVXS-101
D.3.9.4	EV Substance Code	SUB193254
D.3.10	Strength
D.3.10.1	Concentration unit	vector genomes (vg)/mL
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40000000000000
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)	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	No
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

Gene Replacement Therapy Clinical Trial for Patients with Spinal
Muscular Atrophy

E.1.1.1

Medical condition in easily understood language

Patients with Spinal Muscular Atrophy

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

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 safety objective is to assess the safety and tolerability of IT administration of AVXS-101 by the incidence and severity of AEs while determining the optimal dose of AVXS-101 that demonstrates acceptable safety with maximum preliminary efficacy administered by IT
injection. Safety and efficacy will be assessed independently for each age cohort.

E.2.2

Secondary objectives of the trial

The secondary efficacy objective for both age groups is to determine the:
• Proportion of patients that achieve ability to walk without assistance defined as taking at least five steps independently displaying coordination and balance (Bayley Scales of Infant and Toddler Development ).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients ≥6 months and ≤ 60 months (1800 days) of age at time of dosing.
• Diagnostic confirmation by genotype includes lab documentation of homozygous absence of SMN1 exon 7; with exactly three copies of SMN2
2. Negative gene testing for SMN2 gene modifier mutation (c.859G>C)
3. Onset of clinical signs and symptoms consistent with SMA at < 12 months of age
4. Able to sit independently and not standing or walking independently.
5. Meet age-appropriate institutional criteria for use of anesthesia and sedation, as determined necessary by the Investigator
6. Be up-to-date on childhood vaccines
7. Parent(s)/legal guardian(s) willing and able to complete the informed consent process

E.4

Principal exclusion criteria

1. Current or historical ability to stand or walk independently
2. Contraindications for spinal tap procedure or administration of IT therapy
3. Severe contractures as determined by designated Physical Therapist(s) at screening that interfere with either the ability to attain/demonstrate functional measures
4. Severe scoliosis
5. Previous, planned or expected scoliosis repair surgery/procedure within 1 year of dose administration
6. Use of invasive ventilatory support
7. Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two weeks prior to dosing
8. Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods
9. Active viral infection
10. Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization
within two weeks prior to study entry
11. Respiratory infection requiring medical attention, medical intervention or increase in supportive care of any manner within four weeks prior to study entry
12. Severe non-pulmonary/respiratory tract infection within four
weeks before study dosing or concomitant illness that in the opinion of the Principal Investigator (PI) creates unnecessary risks for gene transfer
13. History of bacterial meningitis or brain or spinal cord disease, including tumors, orabnormalities
14. Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
15. Known allergy or hypersensitivity to iodine or iodine-containing products
16. Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis,
immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months of study dosing
17. Inability to withhold use of laxatives or diuretics in the 24 hours prior to dose administration
18. Anti-AAV9 antibody titers >1:50 as determined by enzyme-linked immunosorbent assay
19. Clinically significant abnormal laboratory values

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the proportion of patients ≥6 months and < 24 months at time of dosing that achieve the ability to stand alone, without support for at least 3 seconds (Bayley Scales of Infant and Toddler Motor Development – Gross Motor subset item # 40) up to the 12-month study visit. A Responder for the primary endpoint of standing alone will be defined as per the Bayley Scales of Infant and Toddler Motor Development – Gross Motor subset item #40 – the child stands alone for at least 3 seconds after you release his or her hands.

E.5.1.1

Timepoint(s) of evaluation of this end point

Cohorts 1,2: 12 months
Cohort 3: 15 months

E.5.2

Secondary end point(s)

The secondary endpoint for both patient strata (aged ≥6 months and < 24 months at dosing, aged ≥ 24 and < 60 months at dosing) will be the proportion achieving the ability to walk without assistance, defined as per the Bayley Scales of Infant and Toddler Motor Development – Gross Motor subset item # 43) up to the 12-month study visit. A Responder will be defined as a patient demonstrating achievement of the ability to walk without assistance at any post-procedure visit up to Month 12.

E.5.2.1

Timepoint(s) of evaluation of this end point

Cohorts 1,2: 12 months
Cohort 3: 15 months

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

Yes

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

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)

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

Yes

E.8.1.7.1

Other trial design description

Open-label, Dose Comparison Study

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

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.8.9.2

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