An open, non-controlled, parallel, ascending multiple-dose, multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SOBI003 in pediatric MPS IIIA patients

• Register: EUCTR
• Last refreshed on: 9 November 2020
• Main ID: EUCTR2017-002806-10-NL
• Date of registration: 08/11/2018
• Prospective Registration: Yes
• Primary sponsor: Swedish Orphan Biovitrum AB (publ)
• Public title: An open, non-controlled, parallel, ascending multiple-dose, multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SOBI003 in pediatric MPS IIIA patients
• Scientific title: An open, non-controlled, parallel, ascending multiple-dose, multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SOBI003 in pediatric MPS IIIA patients
• Date of first enrolment: 29/11/2019
• Target sample size: 9
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002806-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Netherlands, Turkey, United States

Contacts

• Name: Anders Bröijersen MD
• Affiliation: Swedish Orphan Biovitrum AB (publ)

• Name: Anders Bröijersen MD
• Affiliation: Swedish Orphan Biovitrum AB (publ)

Key inclusion & exclusion criteria

Inclusion criteria:
MPS IIIA patients, as confirmed by both a documented deficiency in sulfamidase enzyme activity in concordance with a diagnosis of MPS IIIA and normal enzyme activity level of at least one other sulfatase measured in leukocytes, that are =12 to =72 months of age and that have a developmental age =12 months.

Are the trial subjects under 18? yes
Number of subjects for this age range: 9
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients with at least one S298P mutation in the SGSH gene are excluded, as well as patients that have received prior stem cell or gene therapy, or enzyme replacement therapy for MPS IIIA.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Mucopolysaccharidosis Type IIIA or Sanfilippo Syndrome
MedDRA version: 20.1 Level: LLT Classification code 10028094 Term: Mucopolysaccharidosis IH System Organ Class: 100000004850

Intervention(s)

Product Name: Chemically modified recombinant human sulfamidase
Product Code: SOBI003
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: not applicable
CAS Number: NA
Current Sponsor code: SOBI003
Other descriptive name: CHEMICALLY MODIFIED RECOMBINANT HUMAN SULFAMIDASE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: Primary objective:
To evaluate the safety and tolerability of SOBI003 at different dose levels.

Secondary Objective: Secondary objectives:

1. To characterize tthe pharmacokinetics (PK) properties of SOBI003 following single and repeated administration by the use of non-compartmental analysis (NCA)
2. To assess the immunogenicity of SOBI003
3. To assess the pharmacodynamic (PD) effect of different dose levels and treatment duration of SOBI003 on heparan sulfate (HS) levels in
cerebrospinal fluid (CSF), serum and urine
4. To assess the effect of SOBI003 at different dose levels on neurocognition
5. To assess the effect of SOBI003 at different dose levels on adaptive behavior
6. To assess the effect of SOBI003 at different dose levels on gray matter volume
7. To assess the effect of SOBI003 at different dose levels on Quality of Life

Timepoint(s) of evaluation of this end point: Adverse events are recorded from the time of first investigational product administration until last study visit (Week 24).

Blood and urine samples for central laboratory analyses of hematology, clinical chemistry and coagulation are collected at Screening and prior to each infusion at Weeks 1 to 8. Pre-infusion sampling also applies biweekly from Week 10 to 22.

12-lead ECGs are obtained at Screening and prior to and post the infusions on Weeks 1 to 4, 6, 8, 12 and 24.

A physical examination will be performed at Screening, Baseline and at Week 24. General appearance and skin are examined prior to and within 1 hour of completion of each infusion.

Primary end point(s): Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints:

The secondary endpoints to evaluate the primary objective of the safety and tolerability of SOBI003 are:
- Vital signs (blood pressure, heart rate, body temperature, respiratory rate and oxygen saturation)
- Laboratory safety variables (hematology, coagulation, clinical chemistry and urine analysis)

The endpoints relating to the 1st secondary objective are:
- Serum SOBI003 PK parameters at Weeks 1, 4, 12, and 24; tEnd of inf,
CEnd of inf, Cmax, tmax, CPre-dose, CTrough, CL, AUC0-168h, t1/2
- CSF SOBI003 concentration at Weeks 12 and 24

The endpoints relating to the 2nd secondary objective are:
- Occurrence of anti-drug antibodies (ADAs) against SOBI003 in serum
(seroconversion rate, time to seroconversion, transient/persistent). For patients with confirmed ADA positive serum samples, the following additional endpoints apply; ADA titers and IgG subclasses in serum and presence of neutralizing antibodies (NAb) in serum.
- Occurrence of ADAs against SOBI003 in CSF (conversion rate, time to
occurrence, transient/persistent). For patients with confirmed ADA
positive CSF samples, the following additional endpoints apply; ADA
titers and presence of NAb in CSF.

The endpoints relating to the 3rd secondary objective are:
- Change from baseline in CSF HS at Weeks 12 and 24
- Change from baseline in serum HS at Weeks 2, 3, 4, 8, 12 and 24
- Change from baseline in urine HS at Weeks 2, 3, 4, 8, 12 and 24

The endpoints relating to the 4th secondary objective are:
- neurocognitive Development Quotient (DQ) and age-equivalence score (AEq) as assessed by the Bayley Scales of Infant and Toddler Development®, third edition (BSID-III)
- cognitive subtest or the Kaufman Assessment Battery for Children, Second edition (KABC™-II); change from baseline at Week 24.

The endpoint relating to the 5th secondary objective is
- adaptive behavior ageequivalence score (AEq) as assessed by Vineland™ Adaptive Behavior Scales, Expanded Interview Form, Second edition (VABS-II); change from baseline at Week 24.

The endpoint relating to the 6th secondary objective is gray matter volume as assessed by brain volumetric magnetic resonance imaging (MRI); change from baseline at Week 24.

The endpoint relating to the 7th secondary objective is Pediatric Quality of Life Inventory (PedsQL™) total score and PedsQL™ Family Impact Module total score; change from baseline at Week 24.

Timepoint(s) of evaluation of this end point: Timespoints for evaluations:
- Serum concentration vs time profiles are obtained for determination of SOBI003 PK variables at Weeks 1, 4, 12 and 24.
- In addition, serum samples are collected when ADA samples are obtained. SOBI003 concentration in CSF is assessed at Weeks 12 and 24.
- HS is assessed in CSF at Baseline and Weeks 12 and 24.
- HS in serum at Baseline and at Weeks 2 to 4, 8, 12 and 24.
- HS in urine at Screening, Baseline, and at Weeks 2 to 4, 8, 12, and 24.

Secondary ID(s)

2017-002806-10-DE

NCT03423186

SOBI003-001

Source(s) of Monetary Support

Swedish Orphan Biovitrum AB

Ethics review

Status: Approved
Approval date: 29/11/2019
Contact: