Clinical Trials Register

Summary
EudraCT Number:	2019-001283-30
Sponsor's Protocol Code Number:	SPK-3006-101
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-01-20
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 - PEI

A.2

EudraCT number

2019-001283-30

A.3

Full title of the trial

Phase 1/2, dose-escalation study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of SPK-3006 in adults with late-onset Pompe disease

A.3.1

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

A study of safety, tolerability and efficacy of a single intravenous infusion of SPK-3006 in adults with late-onset Pompe disease (type II glycogen storage disease)

A.4.1

Sponsor's protocol code number

SPK-3006-101

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	Spark Therapeutics
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	Spark Therapeutics
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	Spark Therapeutics
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	3737 Market Street, Suite 1300
B.5.3.2	Town/ city	Philadelphia
B.5.3.3	Post code	PA 19104
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrials@sparktx.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/3/19/2175
D.3 Description of the IMP
D.3.2	Product code	SPK-3006
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	SPK-3006
D.3.9.2	Current sponsor code	SPK-3006
D.3.9.4	EV Substance Code	SUB199354
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	1E13
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

Pompe Disease (also known as glycogen storage disease type II)

E.1.1.1

Medical condition in easily understood language

Pompe Disease

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

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 evaluate safety and tolerability of a single intravenous dose of SPK-3006 administered at escalating dose levels to participants with clinically moderate late-onset Pompe disease (LOPD).

E.2.2

Secondary objectives of the trial

To evaluate potential efficacy and bioactivity of SPK-3006.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Be able to understand the purpose and risks of the study and provide
signed and dated informed consent and authorization to use protected
health information (PHI) in accordance with national and local privacy
regulations;
2. Are male or female ≥18 years of age with a confirmed diagnosis (e.g.,
GAA genetic testing) of LOPD, or based on a documented deficiency of
GAA enzyme activity;
3. Have received a marketed ERT for at least the previous 24 months and
maintained a stable dose, frequency and compliance for the past 6
months with no dose variation and no longer improving on ERT;
4. Have clinically moderate, LOPD characteristics;
a. Able to walk ≥75 meters on the 6MWT (assistive devices permitted)
but less than 500 meters assessed at two timepoints prior to initiating
immunosuppression (Day -6) with <10% variance between the
assessments. If the variance is ≥10%, a third timepoint will be
collected;
b. Percentage of the predicted FVC ≥30% and ≤80% in the upright
position;
5. Agree to use reliable contraception for a minimum of 6 months after
administration of SPK-3006 or 12 weeks after the final dose of sirolimus,
whichever occurs later. Female candidates of child-bearing potential
must have a negative pregnancy test prior to initiating
immunosuppression (Day -6) and on Day 0 prior to administration of
SPK-3006. See Section 13 (Appendix 1) for guidance on reliable
contraception and the definition of women of child-bearing potential
(WOCBP);
6. Agree to refrain from blood, plasma, platelets, egg or sperm and organ
donation after receiving SPK-3006.

E.4

Principal exclusion criteria

1. Active hepatitis B and/or C
All candidates must be screened for both active hepatitis B and C,
regardless of prior known history.
a. Screening for hepatitis B
All candidates must have a single sample at Screening for each of the
following tests: hepatitis B surface antigen (HBsAg), total hepatitis B
core antibody (anti-HBc), and a nucleic acid test for hepatitis B virus
DNA (HBV-DNA viral assay)
i. A candidate is not eligible if either HBsAg is positive or HBV-DNA is
positive/detectable.
ii. A candidate is eligible if the anti-HBc is positive and both HBsAg and
HBV-DNA are negative, as this would be consistent with a prior infection
of hepatitis B. Anti-HBc must be obtained in all candidates to
discriminate between acute infection and possible reactivation of
hepatitis B during the trial in candidates with no prior history of
hepatitis B.
iii. A candidate who is currently undergoing antiviral therapy for chronic
hepatitis B is not eligible.
b. Screening for hepatitis C
i. A candidate who is currently undergoing antiviral therapy for chronic
hepatitis C is not eligible.
ii. All other candidates, including those who have never been treated or
who have completed antiviral therapy for chronic hepatitis C must have a
nucleic acid test for hepatitis C viral RNA (HCV-RNA single load assay) at
Screening
• A candidate is not eligible if the HCV-RNA load assay is
positive/detectable.
• Candidates treated with anti-viral therapy for chronic hepatitis C, must
have completed anti-viral therapy at least 6 months prior to Screening
and have a negative HCV-RNA at Screening.
• Candidates with a documented or self-reported history of hepatitis C
must have a single negative HCV-RNA at Screening
2. Significant underlying liver disease. A candidate is not eligible if any
of the following pre-existing diagnoses, which are indicative of
significant underlying liver disease, are present in the medical record
• Liver cirrhosis
• Portal hypertension
• Hepatic encephalopathy
• Gamma-glutamyl transferase (GGT) >1.2X ULN adjusted for age and
gender; or
• Bilirubin >1.2X ULN adjusted for age and gender. Candidates with
asymptomatic elevated bilirubin (e.g., Gilbert syndrome) can be
considered after discussion with the Medical Monitor.
All candidates who do not have the pre-existing diagnoses listed above
must have the following assessments performed at Screening
• Measurement of serum albumin. A candidate is not eligible if the serum
albumin level is below the testing laboratory's lower limit of normal
• Liver fibrosis = stage 3. The following results are indicative of fibrosis
>= stage 3 and exclude the candidate from participation
- FibroScan, with a score > 8.3 kPa units
- FibroTest/ FibroSURE with a result > 0.48
- AST-Platelet Ratio Index (APRI) >1;
Of note, if results from more than one modality for evaluation of liver
fibrosis are available (e.g., results from both FibroScan and FibroSURE
are available) the result from FibroScan should be consulted for
determination of liver fibrosis as it will take precedence over other
modalities.
3. Human immunodeficiency virus (HIV) infection
4. Prior hypersensitivity to rhGAA
5. Pre-existing AAV-Spark100 neutralizing antibody titers >1:1
6. High titer antibody responses to rhGAA (anti-GAA >1:30,000)
7. Participation in a clinical study with an investigational drug in the past
6 months (vaccination studies are accepted; observation studies are
accepted after discussion with the Medical Monitor);
8. Requires any invasive ventilation or requires noninvasive ventilation
while awake and upright;
9. Any change to respiratory muscle strength training within 90 days
prior to informed consent (for participants receiving respiratory muscle
strength training) or initiation of respiratory muscle strength training
prior to Day 0
10. Received any prior vector or gene transfer agent
11. Concomitant use of medication that is contraindicated with sirolimus
(see Section 19.6.4.1), such as, medication known to be a strong or
moderate inducer or inhibitor of CYP3A4 – excluded only during the
sirolimus immunosuppressive period
12. Live vaccines within 30 days prior to informed consent to at least 52
weeks after receiving SPK-3006 infusion
13. Use of systemic immunosuppressive agents (e.g., corticosteroids)
within 30 days prior to informed consent and to Day 0 prior to SPK-3006
administration
14. Active malignancy (except non-melanoma skin cancer)
15. History of liver cancer
16. Pregnant or nursing women
17. Any evidence of an active infection at the time of SPK-3006 infusion
18. Known allergy or hypersensitivity to SPK-3006 investigational
product or sirolimus
19. Any concurrent clinically significant condition that would not allow
the potential participant to complete the follow-up examinations during
the course of the study, or other condition that, in the opinion of the
Investigator and/or Medical Monitor, and/or Sponsor makes the
candidate unsuitable for participation in the study

E.5 End points

E.5.1

Primary end point(s)

• Incidence of AEs and SAEs, clinically significant abnormal laboratory
values, change in vital signs, change in PE, vector shedding in bodily
fluids, liver function tests
• Immune responses against the SPk100 capsid (neutralizing
antibodies) and GAA transgene product (binding and neutralizing
antibodies)

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluation of AEs and SAEs will be ongoing throughout the study.

Laboratory assessments including shedding and liver function tests will occur as detailed in the schedule of assessments in protocol SPK-3006-101.

E.5.2

Secondary end point(s)

• Changes from baseline in the Six-Minute Walk Test (6MWT)
• Changes from baseline in the Forced Vital Capacity (FVC)
• Peak and steady-state vector-derived GAA enzyme levels assessed by
total GAA protein and activity measured in circulation
• Biomarkers of muscle injury and glycogen accumulation (creatine
kinase [CK], urine glucose tetrasaccharide [Hex 4])

E.5.2.1

Timepoint(s) of evaluation of this end point

Designated assessments will be collected as detailed in the schedule of assessments in protocol SPK-3006-101.

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

Yes

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)

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

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

Dose-escalation

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

United States

Denmark

France

Germany

Italy

Netherlands

Spain

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

A participant is considered to have completed the study if he/she has
completed all phases of the study including the Month 60 (Year 5)/EOS
visit procedures. The end of the study is defined as the date of the last
visit of the last participant in the study.

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

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

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)

SPK-3006 is currently being investigated as a single dose treatment. Once the trial is over and the defined long-term follow-up (LTFU) is complete, participants will continue to receive care for Pompe
disease by their treating physician.

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

2020-08-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-22

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

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IMP with orphan designation in the indication
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