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Trial record 4 of 29 for:    GUSB

A Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Therapy in Subjects With Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7)

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ClinicalTrials.gov Identifier: NCT02432144
Recruitment Status : Completed
First Posted : May 1, 2015
Results First Posted : July 30, 2019
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Sly Syndrome
MPS VII
Mucopolysaccharidosis
Mucopolysaccharidosis VII
Intervention Drug: UX003
Enrollment 12
Recruitment Details Participants with mucopolysaccharidosis VII (MPS 7) who were UX003 treatment-naïve or previously enrolled and treated in a prior clinical study of UX003 could enroll into this treatment and extension study provided all eligibility criteria had been met for a given participant.
Pre-assignment Details Ten of 12 participants entered this extension study at study Week 0 with ongoing UX003 treatment for the prior 24 or 48 weeks in study UX003-CL301 [NCT02230566]; 2 participants had a large gap between studies (61 weeks between doses).
Arm/Group Title UX003
Hide Arm/Group Description 4 mg/kg UX003 every other week (QOW)
Period Title: Overall Study
Started 12
Completed [1] 11
Not Completed 1
Reason Not Completed
Participant Non-Compliance             1
[1]
Includes 8 participants who switched to commercially available vestronidase alfa before Week 144.
Arm/Group Title UX003
Hide Arm/Group Description 4 mg/kg UX003 QOW
Overall Number of Baseline Participants 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants
16.56  (5.466)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
8
  66.7%
Male
4
  33.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Hispanic or Latino
6
  50.0%
Not Hispanic or Latino
6
  50.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
White
9
  75.0%
Other, Not Specified
3
  25.0%
Urinary Glycosaminoglycans (uGAG)  
Mean (Standard Deviation)
Unit of measure:  G GAG/g creatinine
Number Analyzed 12 participants
1.54848  (0.413237)
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Hide Description An adverse event (AE) is defined as any untoward medical occurrence, whether or not considered drug related. A serious AE is an AE 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; or is an important medical event. AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), Grade 5 (death). TEAEs were defined as reported AEs with onset during the treatment.
Time Frame From first dose of study drug until 30 days after the last dose of study drug. Mean duration of UX003 treatment was 100.5 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who received at least one dose of investigational product in this study.
Arm/Group Title UX003
Hide Arm/Group Description:
4 mg/kg UX003 QOW
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
12
 100.0%
Serious TEAEs
4
  33.3%
Treatment-Related TEAEs
9
  75.0%
Treatment-Related Serious TEAEs
1
   8.3%
Grade 3 or 4 TEAEs
3
  25.0%
TEAEs Leading to Treatment Discontinuation
0
   0.0%
TEAEs Leading to Study Discontinuation
0
   0.0%
TEAEs Leading to Death
0
   0.0%
2.Secondary Outcome
Title Percent Change From Baseline Over Time in Urinary Glycosaminoglycan (uGAG) Excretion (Liquid Chromatography-Tandem Mass Spectrometry, Dermatan Sulfate)
Hide Description First morning void urine was evaluated for uGAG concentration and normalized to urinary creatinine concentration.
Time Frame Baseline (prior to the first dose of study drug in UX003-CL301), Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who received at least one dose of investigational product in this study; participants with an assessment at given time point.
Arm/Group Title UX003
Hide Arm/Group Description:
4 mg/kg UX003 QOW
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: percentage change in uGAG excretion
Week 0 Number Analyzed 12 participants
-62.19  (16.133)
Week 12 Number Analyzed 11 participants
-67.31  (13.953)
Week 24 Number Analyzed 12 participants
-64.03  (14.669)
Week 36 Number Analyzed 11 participants
-60.58  (23.552)
Week 48 Number Analyzed 10 participants
-57.04  (23.611)
Week 60 Number Analyzed 9 participants
-72.25  (18.609)
Week 72 Number Analyzed 9 participants
-78.52  (10.367)
Week 84 Number Analyzed 8 participants
-80.89  (10.023)
Week 96 Number Analyzed 8 participants
-82.39  (6.011)
Week 108 Number Analyzed 7 participants
-82.19  (6.551)
Week 120 Number Analyzed 5 participants
-88.74  (4.023)
Week 132 Number Analyzed 4 participants
-89.22  (3.662)
Week 144 Number Analyzed 4 participants
-91.62  (1.827)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection UX003
Comments Week 0
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-values are from generalized estimating equation (GEE) model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -62.28
Confidence Interval (2-Sided) 95%
-71.98 to -52.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.946
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection UX003
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-values are from a GEE model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -67.18
Confidence Interval (2-Sided) 95%
-73.49 to -60.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.224
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection UX003
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-values are from a GEE model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -64.12
Confidence Interval (2-Sided) 95%
-71.99 to -56.24
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.016
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UX003
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-values are from a GEE model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -60.80
Confidence Interval (2-Sided) 95%
-72.54 to -49.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.992
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection UX003
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-values are from a GEE model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -57.85
Confidence Interval (2-Sided) 95%
-71.87 to -43.82
Estimation Comments [Not Specified]
Time Frame From first dose of study drug until 30 days after the last dose of study drug. Mean duration of UX003 treatment was 100.5 weeks.
Adverse Event Reporting Description TEAEs, defined as reported AEs with onset during the treatment, are presented.
 
Arm/Group Title UX003
Hide Arm/Group Description 4 mg/kg UX003 QOW
All-Cause Mortality
UX003
Affected / at Risk (%)
Total   0/12 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
UX003
Affected / at Risk (%)
Total   4/12 (33.33%) 
Infections and infestations   
Gastroenteritis  1  1/12 (8.33%) 
Injury, poisoning and procedural complications   
Head Injury  1  1/12 (8.33%) 
Nervous system disorders   
Headache  1  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders   
Asthmatic Crisis  1  1/12 (8.33%) 
Bronchospasm  1  1/12 (8.33%) 
Interstitial Lung Disease  1  1/12 (8.33%) 
Skin and subcutaneous tissue disorders   
Urticaria  1  1/12 (8.33%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
UX003
Affected / at Risk (%)
Total   12/12 (100.00%) 
Blood and lymphatic system disorders   
Eosinophilia  1  1/12 (8.33%) 
Cardiac disorders   
Pericardial Effusion  1  1/12 (8.33%) 
Tachycardia  1  1/12 (8.33%) 
Ear and labyrinth disorders   
Ear Pain  1  2/12 (16.67%) 
Otorrhoea  1  1/12 (8.33%) 
Eye disorders   
Conjunctivitis Allergic  1  2/12 (16.67%) 
Eye Pruritus  1  1/12 (8.33%) 
Lacrimation Increased  1  1/12 (8.33%) 
Gastrointestinal disorders   
Aphthous Ulcer  1  1/12 (8.33%) 
Diarrhoea  1  2/12 (16.67%) 
Dyspepsia  1  1/12 (8.33%) 
Gastrooesophageal Reflux Disease  1  3/12 (25.00%) 
Gingival Bleeding  1  1/12 (8.33%) 
Haematochezia  1  1/12 (8.33%) 
Lip Ulceration  1  1/12 (8.33%) 
Nausea  1  2/12 (16.67%) 
Oesophagitis  1  1/12 (8.33%) 
Tooth Discolouration  1  1/12 (8.33%) 
Tooth Loss  1  1/12 (8.33%) 
Toothache  1  1/12 (8.33%) 
Vomiting  1  4/12 (33.33%) 
General disorders   
Chest Pain  1  1/12 (8.33%) 
Fatigue  1  1/12 (8.33%) 
Gait Disturbance  1  1/12 (8.33%) 
Infusion Site Extravasation  1  5/12 (41.67%) 
Infusion Site Swelling  1  2/12 (16.67%) 
Oedema Peripheral  1  2/12 (16.67%) 
Pyrexia  1  2/12 (16.67%) 
Immune system disorders   
Seasonal Allergy  1  1/12 (8.33%) 
Infections and infestations   
Abscess Neck  1  1/12 (8.33%) 
Acarodermatitis  1  1/12 (8.33%) 
Conjunctivitis  1  1/12 (8.33%) 
Ear Infection  1  2/12 (16.67%) 
Folliculitis  1  1/12 (8.33%) 
Furuncle  1  1/12 (8.33%) 
Impetigo  1  1/12 (8.33%) 
Nasopharyngitis  1  2/12 (16.67%) 
Otitis Externa  1  1/12 (8.33%) 
Otitis Media  1  1/12 (8.33%) 
Otitis Media Acute  1  2/12 (16.67%) 
Pharyngitis  1  1/12 (8.33%) 
Rhinitis  1  3/12 (25.00%) 
Root Canal Infection  1  1/12 (8.33%) 
Sinusitis  1  1/12 (8.33%) 
Soft Tissue Infection  1  1/12 (8.33%) 
Tinea Pedis  1  1/12 (8.33%) 
Tooth Infection  1  1/12 (8.33%) 
Upper Respiratory Tract Infection  1  7/12 (58.33%) 
Viral Infection  1  1/12 (8.33%) 
Injury, poisoning and procedural complications   
Arthropod Bite  1  1/12 (8.33%) 
Fall  1  1/12 (8.33%) 
Head Injury  1  1/12 (8.33%) 
Laceration  1  1/12 (8.33%) 
Ligament Sprain  1  2/12 (16.67%) 
Skin Abrasion  1  2/12 (16.67%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  2/12 (16.67%) 
Back Pain  1  1/12 (8.33%) 
Dactylitis  1  1/12 (8.33%) 
Joint Range Of Motion Decreased  1  1/12 (8.33%) 
Joint Stiffness  1  1/12 (8.33%) 
Joint Swelling  1  1/12 (8.33%) 
Muscle Twitching  1  1/12 (8.33%) 
Pain In Extremity  1  2/12 (16.67%) 
Scoliosis  1  1/12 (8.33%) 
Spinal Instability  1  1/12 (8.33%) 
Trigger Finger  1  1/12 (8.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acrochordon  1  1/12 (8.33%) 
Skin Papilloma  1  1/12 (8.33%) 
Nervous system disorders   
Brain Compression  1  1/12 (8.33%) 
Cervical Cord Compression  1  1/12 (8.33%) 
Headache  1  2/12 (16.67%) 
Hydrocephalus  1  1/12 (8.33%) 
Lethargy  1  2/12 (16.67%) 
Memory Impairment  1  1/12 (8.33%) 
Paraesthesia  1  1/12 (8.33%) 
Sensory Disturbance  1  1/12 (8.33%) 
Sinus Headache  1  1/12 (8.33%) 
Psychiatric disorders   
Insomnia  1  1/12 (8.33%) 
Somnambulism  1  1/12 (8.33%) 
Renal and urinary disorders   
Pollakiuria  1  2/12 (16.67%) 
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/12 (8.33%) 
Bronchospasm  1  1/12 (8.33%) 
Cough  1  4/12 (33.33%) 
Epistaxis  1  1/12 (8.33%) 
Nasal Congestion  1  3/12 (25.00%) 
Rhinitis Allergic  1  2/12 (16.67%) 
Rhinorrhoea  1  2/12 (16.67%) 
Sinus Congestion  1  1/12 (8.33%) 
Sleep Apnoea Syndrome  1  1/12 (8.33%) 
Upper Respiratory Tract Congestion  1  2/12 (16.67%) 
Skin and subcutaneous tissue disorders   
Dermatitis  1  1/12 (8.33%) 
Dermatitis Atopic  1  1/12 (8.33%) 
Erythema  1  1/12 (8.33%) 
Macule  1  1/12 (8.33%) 
Papule  1  1/12 (8.33%) 
Pruritus  1  1/12 (8.33%) 
Rash  1  2/12 (16.67%) 
Rash Maculo-Papular  1  1/12 (8.33%) 
Rash Papular  1  2/12 (16.67%) 
Rash Pruritic  1  1/12 (8.33%) 
Urticaria  1  4/12 (33.33%) 
Vascular disorders   
Hypertension  1  1/12 (8.33%) 
Hypotension  1  1/12 (8.33%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: Ultragenyx Pharmaceutical Inc
Phone: 1-888-756-8567
EMail: medinfo@ultragenyx.com
Layout table for additonal information
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02432144     History of Changes
Other Study ID Numbers: UX003-CL202
2015-001875-32 ( EudraCT Number )
First Submitted: April 22, 2015
First Posted: May 1, 2015
Results First Submitted: July 10, 2019
Results First Posted: July 30, 2019
Last Update Posted: July 30, 2019