Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03811028
Recruitment Status : Recruiting
First Posted : January 21, 2019
Last Update Posted : January 28, 2019
Sponsor:
Information provided by (Responsible Party):
Swedish Orphan Biovitrum

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Sanfilippo Syndrome Type A (MPS IIIA) Drug: SOBI003 Phase 1 Phase 2

Detailed Description:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : January 23, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: SOBI003

SOBI003 solution, 20 mg/mL, is mixed with NaCl 0.9% infusion solution prior to administration. For a bodyweight < 25 kg, the total infusion volume is 100 mL. For a bodyweight ≥ 25 kg, the total infusion volume is 250 mL.

SOBI003 is administered as i.v. infusions given once weekly for a duration of 80 weeks (from Week 25 until Week 104 following the first 24 weeks of SOBI003 administration in the FIH study (SOBI003-001) study. The SOBI003 dose will be adjusted to the highest dose that has been declared safe by the safety review committee on the FIH study.Hence, dose adjustments may occur a couple of times on the extension study until the final decided dose has been determined.

Drug: SOBI003
weekly i.v. infusion
Other Name: Modified recombinant human sulphamidase




Primary Outcome Measures :
  1. Safety will be measured by adverse events frequencies (by type and severity) [ Time Frame: Continuously from the informed consent is signed through study completion, summarized over 18 months. ]

Secondary Outcome Measures :
  1. The observed serum concentration immediately before the start of the next infusion of SOBI003 (CPre-infusion) [ Time Frame: Weeks 38, 52, 78 and 104 ]
  2. The observed serum concentration at the end of infusion of SOBI003 (CEnd of inf) [ Time Frame: Weeks 38, 52, 78 and 104 ]
    The study is an extension study, thus there might be serum concentrations from the previous study at the first assessment (Week 38) in the study

  3. The time of the end of the infusion of SOBI003 (tEnd of inf) [ Time Frame: Weeks 38, 52, 78 and 104 ]
  4. The maximum observed serum concentration (Cmax) [ Time Frame: Weeks 38, 52, 78 and 104 ]
  5. The time at which the maximum serum concentration is observed (tmax) [ Time Frame: Weeks 38, 52, 78 and 104 ]
  6. The minimum observed serum concentration (CTrough) [ Time Frame: Weeks 38, 52, 78 and 104 ]
  7. Clearance (CL) [ Time Frame: Weeks 38, 52, 78 and 104 ]
  8. The area under the plasma concentration-time curve from time 0 to last sample (AUC0-168h) [ Time Frame: Weeks 38, 52, 78 and 104 ]
  9. The half-life (t1/2) [ Time Frame: Weeks 38, 52, 78 and 104 ]
  10. SOBI003 concentration in cerebrospinal fluid [ Time Frame: Weeks 52 and 104 ]
  11. Proportion of patients having anti-drug antibodies in serum [ Time Frame: Weeks 38, 52, 78 and 104 ]
  12. Proportion of patients having anti-drug antibodies in cerebrospinal fluid [ Time Frame: Weeks 52 and 104 ]
  13. Change from baseline in Heparan Sulfate concentration in cerebrospinal fluid [ Time Frame: Weeks 52 and 104 ]
  14. Change from baseline in Heparan sulfate concentration in serum [ Time Frame: Weeks 38, 52, 78 and 104 ]
  15. Change from baseline in Heparan sulfate concentration levels in urine [ Time Frame: Weeks 38, 52, 78 and 104 ]
  16. 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.


  17. Change from baseline in Neurocognitive Development Quotient [ Time Frame: Week 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.


  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 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.


  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. 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).

  23. 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).

  24. 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.

  25. 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. Lower scores indicate better functioning. Min score = 0, and max score = 144.

  26. 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.

  27. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Months to 78 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03811028


Contacts
Layout table for location contacts
Contact: Anders Bröijersén, MD +46 760 011576 anders.broijersen@sobi.com
Contact: Kristin Önnestam, MSC +46 760 011594 kristin.onnestam@sobi.com

Locations
Layout table for location information
United States, California
Children´s Hospital and research center Recruiting
Oakland, California, United States, 94609
Contact: Paul Harmatz, MD         
United States, North Carolina
University of North Carolina hospitals Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Joseph Muenzer, MD         
Turkey
Gazi University Hospital Not yet recruiting
Ankara, Turkey
Contact: Fatih Ezgu, MD         
Sponsors and Collaborators
Swedish Orphan Biovitrum
Investigators
Layout table for investigator information
Principal Investigator: Paul Harmatz, MD Children´s Hospital and Research Center, Oakland

Layout table for additonal information
Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT03811028     History of Changes
Other Study ID Numbers: SOBI003-002
First Posted: January 21, 2019    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Mucopolysaccharidosis III
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases