Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01697319
Recruitment Status : Terminated
First Posted : October 2, 2012
Results First Posted : January 12, 2016
Last Update Posted : January 12, 2016
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Mucopolysaccharidosis IVA
Morquio A Syndrome
MPS IVA
Intervention Drug: BMN 110
Enrollment 16
Recruitment Details  
Pre-assignment Details  
Arm/Group Title BMN 110 at 2.0 mg/kg/Week
Hide Arm/Group Description Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.
Period Title: Primary Phase
Started 16 [1]
Completed 15
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
[1]
One subject enrolled but did not receive a single dose of study drug
Period Title: Extension Phase
Started 15
Completed 0
Not Completed 15
Reason Not Completed
Terminated by Sponsor             15
Arm/Group Title BMN 110 at 2.0 mg/kg/Week
Hide Arm/Group Description Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.
Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
20.7  (8.38)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
5 to 11 years 1
12 to 18 years 8
>=19 years 7
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
7
  43.8%
Male
9
  56.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Hispanic or Latino
4
  25.0%
Not Hispanic or Latino
12
  75.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
American Indian or Alaska Native 0
Asian 2
Native Hawaiian or Other Pacific Islander 0
Black or African American 1
White 12
Other 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
Germany 6
United Kingdom 4
United States 6
1.Primary Outcome
Title Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)
Hide Description FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT Population
Arm/Group Title BMN 110 at 2.0 mg/kg/Week
Hide Arm/Group Description:
Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: % of change
Dominant Hand Wk 24 % Chg from Baseline 1.8  (45.60)
Dominant Hand Wk 48 % Chg from Baseline 23.1  (53.88)
Dominant Hand Wk 72 % Chg from Baseline 37.2  (54.94)
Dominant Hand Wk 96 % Chg from Baseline 22.5  (42.21)
Non-Dominant Hand Wk 24 % Chg from Baseline 13.8  (32.54)
Non-Dominant Hand Wk 48 % Chg from Baseline 6.0  (35.78)
Non-Dominant Hand Wk 72 % Chg from Baseline 49.3  (126.26)
Non-Dominant Hand Wk 96 % Chg from Baseline -2.0  (2.83)
2.Primary Outcome
Title Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)
Hide Description A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT Population
Arm/Group Title BMN 110 at 2.0 mg/kg/Week
Hide Arm/Group Description:
Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: kg
Grip Dominant Hand Wk 24 Chg from Baseline 0.1  (0.89)
Grip Dominant Hand Wk 48 Chg from Baseline -0.3  (0.90)
Grip Dominant Hand Wk 72 Chg from Baseline -0.1  (0.33)
Grip Dominant Hand Wk 96 Chg from Baseline 0.3  (0.23)
Grip Non-Dominant Hand Wk24 Chg from Baseline -0.0  (0.70)
Grip Non-Dominant Hand Wk 48 Chg from Baseline -0.1  (0.66)
Grip Non-Dominant Hand Wk 72 Chg from Baseline 0.1  (0.79)
Grip Non-Dominant Hand Wk 96 Chg from Baseline 0.4  (0.87)
Pinch Dominant Hand Wk 24 Chg from Baseline -0.1  (0.32)
Pinch Dominant Hand Wk 48 Chg from Baseline -0.0  (0.30)
Pinch Dominant Hand Wk 72 Chg from Baseline -0.1  (0.23)
Pinch Dominant Hand Wk 96 Chg from Baseline -0.6 [1]   (NA)
Pinch Non-Dominant Hand Wk 24 Chg from Baseline -0.0  (0.18)
Pinch Non-Dominant Hand Wk 48 Chg from Baseline 0.0  (0.27)
Pinch Non-Dominant Hand Wk 72 Chg from Baseline -0.1  (0.31)
Pinch Non-Dominant Hand Wk 96 Chg from Baseline -0.3  (0.36)
[1]
One observation only
3.Primary Outcome
Title Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)
Hide Description The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT Population
Arm/Group Title BMN 110 at 2.0 mg/kg/Week
Hide Arm/Group Description:
Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: % of change
Wk 24 % Change from Baseline Two Attempts Combined 95.7  (142.37)
Wk 48 % Change from Baseline Two Attempts Combined 53.5  (102.74)
Wk 72 % Change from Baseline Two Attempts Combined 48.3  (145.01)
Wk 96 % Change from Baseline Two Attempts Combined NA [1]   (NA)
[1]
Small sample size and zero denominators
4.Secondary Outcome
Title Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)
Hide Description Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT Population
Arm/Group Title BMN 110 at 2.0 mg/kg/Week
Hide Arm/Group Description:
Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: % of change
Week 24 % Change from Baseline -47.7  (15.40)
Week 48 % Change from Baseline -43.4  (24.82)
Week 72 % Change from Baseline -45.5  (19.67)
Week 96 % Change from Baseline -48.3  (24.13)
Time Frame Study Period
Adverse Event Reporting Description All Adverse Events
 
Arm/Group Title BMN 110 at 2.0 mg/kg/Week
Hide Arm/Group Description Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.
All-Cause Mortality
BMN 110 at 2.0 mg/kg/Week
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
BMN 110 at 2.0 mg/kg/Week
Affected / at Risk (%) # Events
Total   7/15 (46.67%)    
Immune system disorders   
Hypersensitivity  1  1/15 (6.67%)  2
Infections and infestations   
Lower respiratory tract infection  1  1/15 (6.67%)  1
Otitis media  1  1/15 (6.67%)  1
Pneumonia bacterial  1  1/15 (6.67%)  1
Pneumonia mycoplasmal  1  1/15 (6.67%)  1
Injury, poisoning and procedural complications   
Infusion related reaction  1  1/15 (6.67%)  1
Musculoskeletal and connective tissue disorders   
Bone disorder  1  1/15 (6.67%)  1
Nervous system disorders   
Cervical cord compression  1  1/15 (6.67%)  1
Psychiatric disorders   
Sleep disorder  1  1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  1/15 (6.67%)  1
Respiratory failure  1  1/15 (6.67%)  3
Surgical and medical procedures   
Central venous catheterisation  1  1/15 (6.67%)  1
Vascular disorders   
Poor venous access  1  1/15 (6.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BMN 110 at 2.0 mg/kg/Week
Affected / at Risk (%) # Events
Total   15/15 (100.00%)    
Cardiac disorders   
Atrioventricular block first degree  1  1/15 (6.67%)  1
Sinus tachycardia  1  1/15 (6.67%)  1
Tachycardia  1  2/15 (13.33%)  2
Ear and labyrinth disorders   
Ear discomfort  1  2/15 (13.33%)  2
Ear disorder  1  1/15 (6.67%)  1
Ear pain  1  2/15 (13.33%)  3
Otorrhoea  1  1/15 (6.67%)  2
Eye disorders   
Corneal opacity  1  1/15 (6.67%)  1
Dry eye  1  1/15 (6.67%)  1
Eye disorder  1  1/15 (6.67%)  1
Eye pain  1  1/15 (6.67%)  1
Eye pruritus  1  1/15 (6.67%)  1
Eyelid cyst  1  1/15 (6.67%)  1
Eyelid pain  1  1/15 (6.67%)  1
Lacrimation increased  1  1/15 (6.67%)  3
Gastrointestinal disorders   
Abdominal discomfort  1  2/15 (13.33%)  3
Abdominal pain  1  3/15 (20.00%)  7
Abdominal pain upper  1  6/15 (40.00%)  12
Constipation  1  2/15 (13.33%)  2
Diarrhoea  1  7/15 (46.67%)  28
Gastritis  1  1/15 (6.67%)  1
Gastrooesophageal reflux disease  1  1/15 (6.67%)  1
Nausea  1  7/15 (46.67%)  19
Vomiting  1  6/15 (40.00%)  29
General disorders   
Catheter site pain  1  1/15 (6.67%)  1
Chest pain  1  2/15 (13.33%)  2
Device occlusion  1  2/15 (13.33%)  2
Extravasation  1  1/15 (6.67%)  1
Face oedema  1  1/15 (6.67%)  1
Fatigue  1  4/15 (26.67%)  5
Feeling cold  1  2/15 (13.33%)  2
Influenza like illness  1  1/15 (6.67%)  1
Infusion site extravasation  1  1/15 (6.67%)  2
Infusion site pain  1  1/15 (6.67%)  3
Infusion site reaction  1  1/15 (6.67%)  5
Injection site pain  1  1/15 (6.67%)  1
Localised oedema  1  1/15 (6.67%)  1
Malaise  1  1/15 (6.67%)  2
Medical device pain  1  1/15 (6.67%)  1
Nodule  1  1/15 (6.67%)  1
Non-cardiac chest pain  1  2/15 (13.33%)  5
Oedema peripheral  1  1/15 (6.67%)  1
Pain  1  4/15 (26.67%)  5
Pyrexia  1  9/15 (60.00%)  26
Hepatobiliary disorders   
Cholelithiasis  1  1/15 (6.67%)  1
Immune system disorders   
Allergy to arthropod bite  1  1/15 (6.67%)  1
Anaphylactic reaction  1  1/15 (6.67%)  1
Anaphylactoid reaction  1  1/15 (6.67%)  1
Hypersensitivity  1  1/15 (6.67%)  1
Reaction to colouring  1  1/15 (6.67%)  1
Seasonal allergy  1  2/15 (13.33%)  3
Infections and infestations   
Bronchitis  1  2/15 (13.33%)  2
Cystitis  1  1/15 (6.67%)  2
Ear infection  1  2/15 (13.33%)  5
Eye infection  1  1/15 (6.67%)  1
Gastroenteritis  1  2/15 (13.33%)  2
Hordeolum  1  1/15 (6.67%)  1
Influenza  1  1/15 (6.67%)  1
Lower respiratory tract infection  1  3/15 (20.00%)  4
Nasopharyngitis  1  9/15 (60.00%)  19
Otitis externa fungal  1  1/15 (6.67%)  1
Otitis media  1  1/15 (6.67%)  2
Periodontitis  1  1/15 (6.67%)  1
Pulpitis dental  1  1/15 (6.67%)  1
Respiratory tract infection  1  1/15 (6.67%)  1
Rhinitis  1  2/15 (13.33%)  3
Sinusitis  1  3/15 (20.00%)  4
Skin candida  1  1/15 (6.67%)  1
Subcutaneous abscess  1  1/15 (6.67%)  1
Upper respiratory tract infection  1  7/15 (46.67%)  14
Urinary tract infection  1  1/15 (6.67%)  6
Viral infection  1  1/15 (6.67%)  1
Injury, poisoning and procedural complications   
Chillblains  1  1/15 (6.67%)  2
Fall  1  2/15 (13.33%)  3
Heat exhaustion  1  1/15 (6.67%)  1
Limb injury  1  1/15 (6.67%)  1
Tooth fracture  1  1/15 (6.67%)  2
Investigations   
Alanine aminotransferase increased  1  1/15 (6.67%)  1
Blood alkaline phosphatase increased  1  1/15 (6.67%)  2
Blood bilirubin increased  1  1/15 (6.67%)  1
Blood glucose increased  1  1/15 (6.67%)  1
Body temperature increased  1  1/15 (6.67%)  2
Electrocardiogram PR prolongation  1  1/15 (6.67%)  1
QRS axis abnormal  1  2/15 (13.33%)  2
Weight increased  1  1/15 (6.67%)  1
Metabolism and nutrition disorders   
Decreased appetite  1  1/15 (6.67%)  2
Musculoskeletal and connective tissue disorders   
Arthralgia  1  5/15 (33.33%)  28
Back pain  1  5/15 (33.33%)  16
Flank pain  1  1/15 (6.67%)  1
Musculoskeletal chest pain  1  2/15 (13.33%)  2
Musculoskeletal pain  1  2/15 (13.33%)  5
Myalgia  1  4/15 (26.67%)  8
Neck pain  1  2/15 (13.33%)  2
Pain in extremity  1  5/15 (33.33%)  8
Pubic pain  1  1/15 (6.67%)  1
Sensation of heaviness  1  1/15 (6.67%)  2
Tenosynovitis  1  1/15 (6.67%)  1
Nervous system disorders   
Burning sensation  1  1/15 (6.67%)  1
Clonus  1  1/15 (6.67%)  2
Dizziness  1  4/15 (26.67%)  10
Headache  1  11/15 (73.33%)  42
Hypoaesthesia  1  1/15 (6.67%)  3
Lethargy  1  2/15 (13.33%)  3
Paraesthesia  1  2/15 (13.33%)  2
Somnolence  1  1/15 (6.67%)  1
Psychiatric disorders   
Anxiety  1  1/15 (6.67%)  1
Depressed mood  1  1/15 (6.67%)  1
Depression  1  1/15 (6.67%)  1
Restlessness  1  1/15 (6.67%)  1
Renal and urinary disorders   
Dysuria  1  1/15 (6.67%)  3
Nephrolithiasis  1  1/15 (6.67%)  3
Reproductive system and breast disorders   
Dysmenorrhoea  1  1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/15 (6.67%)  2
Cough  1  6/15 (40.00%)  15
Dyspnoea  1  2/15 (13.33%)  4
Hypoxia  1  1/15 (6.67%)  1
Nasal congestion  1  5/15 (33.33%)  10
Nasal obstruction  1  1/15 (6.67%)  1
Oropharyngeal pain  1  4/15 (26.67%)  14
Respiratory failure  1  1/15 (6.67%)  2
Restrictive pulmonary disease  1  2/15 (13.33%)  2
Rhinorrhoea  1  3/15 (20.00%)  3
Sinus congestion  1  1/15 (6.67%)  1
Tachypnoea  1  1/15 (6.67%)  1
Throat irritation  1  1/15 (6.67%)  1
Wheezing  1  2/15 (13.33%)  3
Skin and subcutaneous tissue disorders   
Acne  1  2/15 (13.33%)  2
Dermatitis  1  1/15 (6.67%)  1
Dermatitis allergic  1  1/15 (6.67%)  1
Erythema  1  1/15 (6.67%)  1
Pigmentation disorder  1  1/15 (6.67%)  1
Pruritus  1  1/15 (6.67%)  6
Pruritus generalised  1  1/15 (6.67%)  1
Rash  1  3/15 (20.00%)  3
Rash follicular  1  1/15 (6.67%)  1
Skin disorder  1  1/15 (6.67%)  1
Surgical and medical procedures   
Tooth extraction  1  1/15 (6.67%)  1
Vascular disorders   
Haematoma  1  1/15 (6.67%)  1
Hypotension  1  1/15 (6.67%)  1
Pallor  1  1/15 (6.67%)  1
Poor venous access  1  2/15 (13.33%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: BioMarin Medical Information Services
Organization: BioMarin Pharmaceutical Inc.
Phone: 800-983-4587
EMail: medinfo@bmrn.com
Layout table for additonal information
Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01697319     History of Changes
Other Study ID Numbers: MOR-006
2011-005703-33 ( EudraCT Number )
First Submitted: September 17, 2012
First Posted: October 2, 2012
Results First Submitted: October 12, 2015
Results First Posted: January 12, 2016
Last Update Posted: January 12, 2016