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Study to Evaluate the Safety and Efficacy of Adalimumab in MPS I, II, and VI

Primary Purpose

Mucopolysaccharidosis I, Mucopolysaccharidosis II, Mucopolysaccharidosis VI

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Adalimumab Injection [Humira]
Saline Solution for Injection
Sponsored by
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis I

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female ≥5 years of age;
  • Diagnosis of MPS I, II or VI;
  • Treatment with ERT for ≥1 year or no treatment with ERT for ≥1 year;
  • Weight ≥15 kg;
  • Significant bodily pain reported by the CHQ-PF50 or SF-36 (> 1 SD more severe [below] than the general population mean);
  • ≥ 3 joints with limitations in motion; and Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided.

Exclusion Criteria:

  • History of HCT less than 2 years prior to enrollment;
  • Immune suppression therapy less than 1 year prior to enrollment;
  • Active graft versus host disease;
  • Current diagnosis or history of lymphoma or other malignancy;
  • Current active infection;
  • History of serious opportunistic infection (e.g., bacterial [Legionella and Listeria]; tuberculosis [TB]; invasive fungal infections; or viral, parasitic, and other opportunistic infections);
  • Positive TB skin test, positive Quantiferon-TB Gold TB test, positive chest X-ray, or a recent exposure to TB
  • Congestive heart failure defined by an ejection fracture <50% measured by ECHO;
  • Demyelinating disorders (e.g., central nervous system [CNS] disorders including multiple sclerosis and optic neuritis and peripheral nervous system disorders including Guillain-Barre syndrome);
  • Hematologic abnormalities (e.g., pancytopenia, aplastic anemia);
  • Hepatitis B infection (active or chronic carrier);
  • Latex sensitivity;
  • Pregnancy or breastfeeding;
  • Known or suspected allergy to adalimumab or related products;
  • Participation in simultaneous therapeutic study that involves an investigational study drug or agent within 4 weeks of study enrollment;
  • Requirement for live vaccine exposure that would be expected to occur during the time frame of the study; or
  • Any other social or medical condition that the Investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study.

Sites / Locations

  • The Lundquist Institute at Harbor-UCLA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Adalimumab

Placebo

Open-label adalimumab

Arm Description

20 mg subQ every other week (weight 15to <30 kg) 40 mg subQ every other week (weight ≥30 kg). Non-responders will be escalated to weekly dosing.

Saline placebo comparator

Open-label extension of adalimumab dose

Outcomes

Primary Outcome Measures

Pain - 16 weeks
Mean difference in bodily pain measured by the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50) or the Medical Outcomes Study - Short Form 36 (SF-36) in treatment versus placebo at 16 weeks
Adalimumab trough
Percentage of subjects who achieve a goal trough concentration of adalimumab with every other week dosing

Secondary Outcome Measures

Joint range-of-motion - 16 weeks
Percentage of subjects who achieve a 5 degree or more improvement in joint range-ot-motion in treatment versus placebo at 16 weeks.
Pain - 52 weeks
Mean difference in bodily pain measured by the CHQ-PF50 or the SF-36 at 52 weeks compared to baseline.
Joint range-of-motion - 52 weeks
Percentage of subjects who achieve a 5 degree or more improvement in joint range-ot-motion at 52 weeks compared to baseline.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
Percentage of subjects who develop an AE and/or SAE

Full Information

First Posted
May 11, 2017
Last Updated
March 20, 2023
Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03153319
Brief Title
Study to Evaluate the Safety and Efficacy of Adalimumab in MPS I, II, and VI
Official Title
Phase 1/2 Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II, and VI
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 5, 2017 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of adalimumab compared to placebo on the change from baseline in joint and skeletal disease in children and adults with mucopolysaccharidosis (MPS) I, II or VI.
Detailed Description
This study is a randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of adalimumab compared to placebo on the change from baseline in joint and skeletal disease in children and adults with mucopolysaccharidosis (MPS) I, II or VI. Children and adults diagnosed with MPS I, II or VI, with significant joint restrictions and pain will be randomized to adalimumab treatment or placebo treatment for the first 16 weeks. This will be followed by a 32-week open label adalimumab treatment phase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis I, Mucopolysaccharidosis II, Mucopolysaccharidosis VI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Adalimumab
Arm Type
Experimental
Arm Description
20 mg subQ every other week (weight 15to <30 kg) 40 mg subQ every other week (weight ≥30 kg). Non-responders will be escalated to weekly dosing.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Saline placebo comparator
Arm Title
Open-label adalimumab
Arm Type
Experimental
Arm Description
Open-label extension of adalimumab dose
Intervention Type
Drug
Intervention Name(s)
Adalimumab Injection [Humira]
Intervention Description
Investigational Drug
Intervention Type
Drug
Intervention Name(s)
Saline Solution for Injection
Intervention Description
Placebo Comparator
Primary Outcome Measure Information:
Title
Pain - 16 weeks
Description
Mean difference in bodily pain measured by the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50) or the Medical Outcomes Study - Short Form 36 (SF-36) in treatment versus placebo at 16 weeks
Time Frame
16 weeks
Title
Adalimumab trough
Description
Percentage of subjects who achieve a goal trough concentration of adalimumab with every other week dosing
Time Frame
32 weeks
Secondary Outcome Measure Information:
Title
Joint range-of-motion - 16 weeks
Description
Percentage of subjects who achieve a 5 degree or more improvement in joint range-ot-motion in treatment versus placebo at 16 weeks.
Time Frame
16 weeks
Title
Pain - 52 weeks
Description
Mean difference in bodily pain measured by the CHQ-PF50 or the SF-36 at 52 weeks compared to baseline.
Time Frame
52 weeks
Title
Joint range-of-motion - 52 weeks
Description
Percentage of subjects who achieve a 5 degree or more improvement in joint range-ot-motion at 52 weeks compared to baseline.
Time Frame
52 weeks
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
Description
Percentage of subjects who develop an AE and/or SAE
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female ≥5 years of age; Diagnosis of MPS I, II or VI; Treatment with ERT for ≥1 year or no treatment with ERT for ≥1 year; Weight ≥15 kg; Significant bodily pain reported by the CHQ-PF50 or SF-36 (> 1 SD more severe [below] than the general population mean); ≥ 3 joints with limitations in motion; and Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided. Exclusion Criteria: History of HCT less than 2 years prior to enrollment; Immune suppression therapy less than 1 year prior to enrollment; Active graft versus host disease; Current diagnosis or history of lymphoma or other malignancy; Current active infection; History of serious opportunistic infection (e.g., bacterial [Legionella and Listeria]; tuberculosis [TB]; invasive fungal infections; or viral, parasitic, and other opportunistic infections); Positive TB skin test, positive Quantiferon-TB Gold TB test, positive chest X-ray, or a recent exposure to TB Congestive heart failure defined by an ejection fracture <50% measured by ECHO; Demyelinating disorders (e.g., central nervous system [CNS] disorders including multiple sclerosis and optic neuritis and peripheral nervous system disorders including Guillain-Barre syndrome); Hematologic abnormalities (e.g., pancytopenia, aplastic anemia); Hepatitis B infection (active or chronic carrier); Latex sensitivity; Pregnancy or breastfeeding; Known or suspected allergy to adalimumab or related products; Participation in simultaneous therapeutic study that involves an investigational study drug or agent within 4 weeks of study enrollment; Requirement for live vaccine exposure that would be expected to occur during the time frame of the study; or Any other social or medical condition that the Investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lynda Polgreen, MD
Organizational Affiliation
The Lundquist Institute at Harbor-UCLA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Lundquist Institute at Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Study to Evaluate the Safety and Efficacy of Adalimumab in MPS I, II, and VI

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