Clinical Trials Register

Summary
EudraCT Number:	2020-000095-38
Sponsor's Protocol Code Number:	AVXS-101-CL-303
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-03-18
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

2020-000095-38

A.3

Full title of the trial

Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients with Spinal Muscular Atrophy Type 1 with One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion

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 Type 1 with One or Two SMN2 Copies

A.4.1

Sponsor's protocol code number

AVXS-101-CL-303

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, Suite 200
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	Unite224804 9762
B.5.6	E-mail	MGegenhuber108@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	Infusion
D.3.4.1	Specific paediatric formulation	Yes
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	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	range
D.3.10.3	Concentration number	20000000000000 to 60000000000000
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 Type 1

E.1.1.1

Medical condition in easily understood language

Patients with Spinal Muscular Atrophy Type 1

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

• Determine efficacy by demonstrating achievement of developmental milestone of functional independent sitting for at least 30 seconds at the 18 months of age.
• Determine the efficacy based on survival at 14 months of age. Survival is defined by avoidance of combined endpoint of either (a) death or (b) permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation, so defined, is considered a surrogate for death.

E.2.2

Secondary objectives of the trial

• Determine the ability to thrive defined as achieving all of the following at 18 months of age:
o Does not receive nutrition through mechanical support or other non-oral method
o Ability to tolerate thin liquids as demonstrated through a formal swallowing test
o Maintains weight (> third percentile for age and gender)
• Determine the ability to remain independent of ventilatory support, defined as requiring no daily ventilator support/usage at 18 months of age

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients with SMA Type 1 as determined by the diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations and 1 or 2 copies of SMN2 (inclusive of the known SMN2 gene modifier mutation (c.859G>C).
• Patients must be < 6 months (< 180 days) of age at the time of infusion
• Patients must have a swallowing evaluation test performed prior to administration of gene replacement therapy

E.4

Principal exclusion criteria

• Pulse oximetry < 96% saturation at screening while the patient is awake or asleep without any supplemental oxygen or respiratory support.
• Tracheostomy or current use or requirement of non-invasive ventilatory support averaging ≥ 6 hours daily over the 7 days prior to the screening visit; or ≥ 6 hours/day on average during the screening period or requiring ventilatory support while awake over the 7 days prior to screening or at any point during the screening period prior to dosing.
• Patients with signs of aspiration/inability to tolerate non-thickened- liquids based on a formal swallowing test performed as part of screening. Patients with a gastrostomy tube who pass the swallowing test will be allowed to enroll in the study
• Participation in recent SMA treatment clinical study (with the exception of observational
Cohort studies or non-interventional studies) or receipt of an investigational or commercial
compound, product, or therapy administered with the intent to treat SMA (e.g., nusinersen, valproic acid) at any time prior to screening for this study. Oral β-agonists must be discontinued at least 30 days before gene therapy dosing. Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable.
• Gestational age at birth < 35 weeks.

E.5 End points

E.5.1

Primary end point(s)

• The proportion of patients that achieve functional independent sitting for at least 30 seconds at the 18 months of age study visit. It is defined by the Bayley Scales of Infant and Toddler Development (Version 3), confirmed by video recording, as a patient who sits up straight with the head erect for at least 30 seconds.
• The survival at 14 months of age. Survival is defined by the avoidance of the combined endpoint of either (a) death or (b) permanent ventilation, which is defined by tracheostomy or by the requirement of ≥ 16 hours of respiratory assistance per day for ≥ 14 consecutive days in the absence of an acute reversible illness, excluding perioperative ventilation. Permanent ventilation, so defined, is considered a surrogate for death.

E.5.1.1

Timepoint(s) of evaluation of this end point

18 months for achieving functional sitting for at least 30 seconds
14 months of age for survival

E.5.2

Secondary end point(s)

• The proportion of patients maintaining the ability to thrive, defined as the ability to tolerate thin liquids (as demonstrated through a formal swallowing test) and to maintain weight (based on WHO Child Growth Standards for age and gender) without need of gastrostomy or other mechanical or non-oral nutritional support at 18 months of age.
• The proportion of patients who are independent of ventilatory support, defined as requiring no daily ventilator support/usage at 18 months of age, excluding acute reversible illness and perioperative ventilation, as defined above through assessment of actual usage data captured from the device (Phillips Trilogy).

E.5.2.1

Timepoint(s) of evaluation of this end point

18 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)

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

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, single-arm, single-dose

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

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

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.4.2

For a multinational trial

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)

After the End of Trial visit, eligible patients will be asked to rollover into the long-term follow up trial.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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