Skip to main content
OpenTrials
Completed

NCT Number: NCT03811028

A Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients

MPS IIIA, also known as Sanfilippo A, is an inherited lysosomal storage disease (LSD). MPS IIIA is caused by a deficiency in sulfamidase, one of the enzymes involved in the lysosomal degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The natural course of MPS IIIA is characterized by devastating neurodegeneration with initially mild somatic involvement. The aim of the present study is to assess the safety, tolerability and efficacy of long-term SOBI003 treatment. SOBI003 is a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Sanfilippo Syndrome Type A (MPS IIIA) Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Genetic Diseases, Inborn Lysosomal Storage Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis III Nutritional and Metabolic Diseases Skin and Connective Tissue Diseases

Age range

18 month–78 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Gazi University Hospital, Ankara, Turkey (Türkiye)

Loading trial locations.

About this study

This is an open, single-arm, multicenter extension study to assess the safety, tolerability and efficacy of long-term SOBI003 treatment in pediatric MPS IIIA patients. The study is an extension of the First in Human (FIH) SOBI003-001 study, allowing continuous treatment of SOBI003 for up to 2 years. Study patients who complete Week 24 of the FIH study (SOBI003-001) will be invited to continue to Week 25 in the extension study.

When entering the extension study, these patients will receive the highest dose that has been declared safe in the ongoing FIH study (SOBI003-001). Upon completion of the FIH study, an analysis aimed at selecting the dose for forthcoming studies will take place. Once the dose has been selected, this dose will be applied to all patients enrolled in the extension study. The total duration of the extension study for an individual patient is 80 weeks, resulting in a total of 104 weeks (2 years) of SOBI003 treatment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Completion of study SOBI003-001
  • Informed consent obtained from the patient´s legally authorized representative

Exclusion criteria

  • If, in the opinion of the investigator, there are patient specific safety concerns that contraindicates further treatment with SOBI003

Treatment and study plan

SOBI003

Drug

weekly i.v. infusion

Other names: Modified recombinant human sulphamidase

Primary outcomes

  1. Safety as Measured by Adverse Events Frequencies (by Type and Severity)

    Time frame: From infusion week 25 up to week 104

    Number of adverse events, by type and severity, from week 25 up to week 104

Secondary outcomes

  1. The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003

    Time frame: Weeks 38, 52, 78 and 104

    The observed SOBI003 serum concentration immediately before the start of infusion of SOBI003 (CPre-dose) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  2. The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003

    Time frame: Weeks 38, 52, 78 and 104

    The observed SOBI003 serum concentration at the end of infusion of SOBI003 (CEnd of inf) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  3. The Time of the End of the Infusion of SOBI003

    Time frame: Weeks 38, 52, 78 and 104

    The time of the end of infusion of SOBI003 (tEnd of inf) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  4. The Maximum Observed Serum Concentration of SOBI003

    Time frame: Weeks 38, 52, 78 and 104

    The maximum observed serum concentration of SOBI003 (Cmax) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  5. The Time at Which the Maximum Serum Concentration of SOBI003 is Observed

    Time frame: Weeks 38, 52, 78 and 104

    The time after start of infusion at which the maximum serum concentration is observed (tmax) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  6. The Minimum Observed Serum Concentration of SOBI003

    Time frame: Weeks 38, 52, 78 and 104

    The minimum observed serum concentration of SOBI003 (CTrough) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  7. Clearance

    Time frame: Weeks 38, 52, 78 and 104

    Clearance (CL) of SOBI003 Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  8. Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours

    Time frame: 0,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Weeks 38, 52, 78 and 104

    Area under the SOBI003 serum concentration-time curve from time 0 to 168 hours (AUC 0-168h) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  9. The Half-life

    Time frame: Weeks 38, 52, 78 and 104

    The half-life of SOBI003 in serum (T1/2) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

  10. SOBI003 Concentration in Cerebrospinal Fluid

    Time frame: Weeks 52 and 104

    Concentration of SOBI003 in cerebrospinal fluid

  11. Number of Patients Having Anti-drug Antibodies in Serum

    Time frame: Weeks 38, 52, 78 and 104

    Number of patients in each dose group having anti-drug antibodies in serum

  12. Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid

    Time frame: Weeks 52 and 104

    Number of patients in each dose group having anti-drug antibodies cerebrospinal fluid

  13. Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid

    Time frame: Weeks 52 and 104

    Change from baseline, in percent, of Heparan Sulfate levels in cerebrospinal fluid

  14. Change From Baseline in Heparan Sulfate Levels in Serum

    Time frame: Weeks 38, 52, 78 and 104

    Change from baseline in Heparan sulfate, in mg/L, levels in serum

  15. Change From Baseline in Heparan Sulfate Levels in Urine

    Time frame: Weeks 38, 52, 78 and 104

    Change from baseline in Heparan sulfate levels, in g/mol, in urine

  16. Change From Baseline in Neurocognitive Development Quotient

    Time frame: Weeks 52 and 104

    Quotient between age equivalent score and age, 0 - 100%, where high values are desirable. The age equivalent score represent the age of the typical and normal individual who would achieve the same result as the one who was tested The age equivalent scores are assessed by the Bayley Scales of Infant and Toddler Development®, third edition cognitive subtest or the Kaufman Assessment Battery for Children, Second edition.

    The Bayley Scales of Infant and Toddler Development-Third Edition is an individually administered test designed to assess developmental functioning of infants and toddlers. The Bayley-III assesses development in five areas: cognitive, language, motor,social-emotional, and adaptive behavior.

    The Kaufman Assessment Battery for Children (K-ABC) is a clinical instrument for assessing cognitive development.

    These results are truly "unitless"/"dimensionless" because they represents quotients of values from the same scale, which means that the units in the denominator and

  17. Change From Baseline in Age-equivalence Score

    Time frame: Week 52 and 104

    The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by the Bayley Scales of Infant and Toddler Development®, third edition cognitive subtest or the Kaufman Assessment Battery for Children, Second edition. The Bayley Scales of Infant and Toddler Development-Third Edition is an individually administered test designed to assess developmental functioning of infants and toddlers. The Bayley-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior. The Kaufman Assessment Battery for Children (K-ABC) is a clinical instrument for assessing cognitive development.

  18. Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.

    Time frame: Week 52 and 104

    The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by Vineland™ Adaptive Behavior Scales, Expanded Interview Form, Second edition (VABS-II). The Vineland is designed to measure adaptive behavior of individuals from birth to age 90. The Vineland-II contains 5 domains each with 2-3 subdomains. The main domains are: Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior.

  19. Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.

    Time frame: Week 52 and 104

    The age equivalent score represents the age in months of the typical and normal individual who would achieve the same result as the one who was tested.

    The age equivalent scores are assessed either 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) depending on chronological age of the subject. Quotient between age equivalent score and age, 0 - 100%, where high values are desirable.

    The BSID-III is an individually administered test designed to assess developmental functioning of infants and toddlers. The BSID-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior.

    The KABC-II is a clinical instrument for assessing cognitive development. The unit and measurement is the same in both scales (BSID-III and KABC-II): Age-equivalent score.

  20. Age-equivalence Score as Assessed by VABS-II

    Time frame: Week 52 and 104

    The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested.

    The age equivalent scores are assessed by Vineland™ Adaptive Behavior Scales, Expanded Interview Form, Second edition (VABS-II). The Vineland is designed to measure adaptive behavior of individuals from birth to age 90.

    The Vineland-II contains 5 domains each with 2-3 subdomains. The main domains are: Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior.

  21. Change From Baseline in Age-equivalence Score as Assessed by VABS-II

    Time frame: Week 52 and 104

    The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested.

    The age equivalent scores are assessed by Vineland™ Adaptive Behavior Scales, Expanded Interview Form, Second edition (VABS-II). The Vineland is designed to measure adaptive behavior of individuals from birth to age 90.

    The Vineland-II contains 5 domains each with 2-3 subdomains. The main domains are: Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior.

  22. Change From Baseline in Gray Matter Volume

    Time frame: Week 52 and 104

    Grey matter contains most of the brain's neuronal cell bodies. The grey matter includes regions of the brain involved in muscle control, and sensory perception such as seeing and hearing, memory, emotions, speech, decision making, and self-control. The gray matter volume will be measured by volumetric magnetic resonance imaging (MRI) at weeks 52 and 104.

  23. Pediatric Quality of Life Inventory (PedsQL™) Total Score

    Time frame: Week 52 and 104

    Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. Lower scores indicate better functioning. Min score = 0, and max score = 144.

  24. Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score

    Time frame: Week 52 and 104

    Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. Higher scores indicate better functioning. Min score = 0, and max score = 144.

  25. PedsQL™ Family Impact Module Total Score

    Time frame: Week 52 and 104

    Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. The Total Score is the sum of all 36 items in the test divided by the number of items answered. Higher scores indicate better functioning. Min score = 0, and max score = 144.

  26. Change From Baseline in PedsQL™ Family Impact Module Total Score

    Time frame: Week 52 and 104

    Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. The Total Score is the sum of all 36 items in the test divided by the number of items answered. Higher scores indicate better functioning.

Sponsors and collaborators

Lead sponsor

Swedish Orphan Biovitrum

Industry

Registry information

Official study title

An Open, Single-arm, Multicenter Extension Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Jan 22, 2019
Registry last updated
Feb 25, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.