An Open-Label Phase 1/2 Study to Assess the Safety, Efficacy and Dose of Study Drug UX003 Recombinant Human Beta-glucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)
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|ClinicalTrials.gov Identifier: NCT01856218|
Recruitment Status : Completed
First Posted : May 17, 2013
Results First Posted : January 5, 2018
Last Update Posted : January 4, 2019
UX003-CL201 is an open-label Phase 1/2 study to assess the safety, efficacy, and dose of UX003 in MPS 7 patients via intravenous (IV) administration every other week (QOW) for 36 weeks with up to an additional 36 weeks from the optional continuation period. Up to 5 participants, who are between 5 and 30 years of age inclusive, will be enrolled and treated with UX003.
The initial 12-week treatment period will be followed by a 24-week forced dose titration period to assess the optimal dose. Participants who complete both the initial treatment and forced dose titration periods will continue treatment in a 36- week continuation period.
|Condition or disease||Intervention/treatment||Phase|
|Mucopolysaccharidosis Type 7||Drug: UX003||Phase 1 Phase 2|
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label Phase 1/2 Study to Assess the Safety, Efficacy and Dose of UX003 rhGUS Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)|
|Study Start Date :||November 2013|
|Actual Primary Completion Date :||July 2016|
|Actual Study Completion Date :||July 2016|
During the initial 14-week treatment period of the study, participants receive 2 mg/kg UX003 every other week (QOW) for 12 weeks. At Week 14, participants continue on UX003 therapy and begin a forced dose titration period for an additional 24 weeks at the dose sequence of 1, 4, and 2 mg/kg UX003 QOW as follows: 1 mg/kg UX003 for 8 weeks beginning on Week 14; then 4 mg/kg UX003 for 8 weeks beginning on Week 22; then 2 mg/kg UX003 for 8 weeks beginning on Week 30. Following the 24 week forced dose titration period, participants who continue on treatment (continuation period) received 2 mg/kg UX003 QOW beginning at Week 38 for up to an additional 36 weeks.
After the first phase of the study, participants who elect to continue drug treatment are transitioned to the long-term extension phase, where they are treated with UX003 at 4 mg/kg beginning at Week 74, for up to an additional 168 weeks.
- Percentage Change From Baseline in Urinary Glycosaminoglycan (uGAG) Dermatan Sulfate [ Time Frame: Baseline, Week 14, Week 22, Week 30, Week 38, Week 72, and end of study (up to Week 132) ]Percentage change from baseline in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate.
- Percentage Change From Baseline in uGAG Chondroitin Sulfate [ Time Frame: Baseline, Week 14, Week 22, Week 30, Week 38, Week 72, and end of study (up to Week 132) ]Percentage change from baseline in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-chondroitin sulfate.
- Number of Participants With Any ≥ 50% Decrease in uGAG [ Time Frame: up to Week 132 ]Participants with a ≥ 50% decrease in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate or chondroitin sulfate.
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Study/Treatment Discontinuations [ Time Frame: Up to 242 weeks + 30 days. SAEs were recorded beginning at the time the subject signed the informed consent form through 30 days following the last study visit. Non-serious AEs were recorded from the time of informed consent through the last study visit. ]Adverse Event (AE): any untoward medical occurrence in a subject, whether or not considered drug related. SAE: an AE or suspected adverse reaction that at any dose results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. Other important medical events may also, in the opinion of the Investigator, be considered SAEs. An AE was considered a TEAE if it occurred on or after the first dose, and was not present prior to the first dose, or it was present at the first dose but increased in severity during the study. Events recorded as either possibly, probably, or definitely related to treatment were categorized as related. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.03.
- Acceptable Dose as Determined by Total uGAG Excretion Using a Forced Dose Titration Regimen [ Time Frame: Week 36 ]The choice of the dose of UX003 QOW for the Long-Term Extension Phase was based on a preliminary efficacy analysis at Week 36 prior to all 3 participants completing the Forced-dose Titration Period of the First Phase of the study.
- Change From Baseline at Week 36 in Six-Minute Walk Test (6MWT) [ Time Frame: Baseline, Week 36 ]The total distance walked (meters) in a 6-minute period was measured once each test day. The test was conducted using a pre-measured walking course according to administration guidelines established by the American Thoracic Society (ATS 2002). Participants who could not walk could omit this test.
- Percent of Predicted Normal Distance Walked [ Time Frame: 36 Weeks ]The percent of predicted normal distance walked (based on published normative data) in the total distance walked in a six-minute period.
- Change From Baseline at Week 36 in the 3-Minute Stair Climb Test (3MSCT) [ Time Frame: Baseline, Week 36 ]The number of stairs climbed within a 3-minute period was assessed once each test day using available hospital stairs. Participants who could not climb stairs could omit this test.
- Change From Baseline at Week 36 in Pulmonary Function Testing (Spirometry) [ Time Frame: Baseline, Week 36 ]The following spirometry tests were administered to participants who did not require invasive ventilatory support or have a tracheostomy in accordance with American Thoracic Society/European Respiratory society (ATS/ERS) guidelines: forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), maximum voluntary ventilation in one minute (MVV1). Invasive ventilation is defined as any form of ventilatory support applied with the use of an endotracheal tube.
- Change From Baseline at Week 36 in Growth Velocity for Height and Weight [ Time Frame: Baseline, Week 36 ]Growth velocity (for males ≤18 years and females ≤15) was calculated from anthropometric measurements and compared with pretreatment growth velocity when available. Z-scores and percentiles were calculated using Centers for Disease Control (CDC) growth chart.
- Change From Baseline at Week 36 in Shoulder Range of Motion (Goniometry) [ Time Frame: Baseline, Week 36 ]The maximum passive shoulder range of motion in both flexion and extension will be measured in degrees using a goniometer.
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): NCT01856218
|Manchester Academic Health Science Centre|
|Manchester, United Kingdom|
|Principal Investigator:||Simon Jones, MD||Univeristy of Manchester|