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Study of BMN 110 in Pediatric Patients < 5 Years of Age With Mucopolysaccharidosis IVA (Morquio A Syndrome)

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: NCT01515956
Recruitment Status : Completed
First Posted : January 24, 2012
Results First Posted : July 6, 2017
Last Update Posted : August 10, 2017
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 15
Recruitment Details  
Pre-assignment Details  
Arm/Group Title BMN110 2.0 mg/kg/Week
Hide Arm/Group Description Weekly intravenous infusions of BMN 110 at a dose of 2.0 mg/kg for 52 consecutive weeks. Each infusion will be administered over a period of approximately 4 hours.
Period Title: Overall Study
Started 15
Completed 15
Not Completed 0
Arm/Group Title BMN110 2.0 mg/kg/Week
Hide Arm/Group Description 2.0 mg/kg/week
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
3.1  (1.34)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
0 to <3 years 7
>=3 to <5 years 8
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
8
  53.3%
Male
7
  46.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Hispanic or Latino
1
   6.7%
Not Hispanic or Latino
14
  93.3%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
Asian 4
White 10
Other 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
Italy 2
United Kingdom 6
United States 7
Urinary Keratan Sulfate Measures  
Mean (Standard Deviation)
Unit of measure:  Ug/mg
Number Analyzed 15 participants
35.9  (12.32)
1.Primary Outcome
Title To Evaluate Safety and Tolerability of Infusions of BMN 110 at a Dose of 2.0 mg/kg/Week Over a 52-week Period in MPS IVA Subjects Less Than 5 Years of Age at Time of First Study Drug Infusion
Hide Description Number of Participants Experiencing Adverse Events
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title BMN110 2.0 mg/kg/Week
Hide Arm/Group Description:
BMN110 2.0 mg/kg/week
Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
15
 100.0%
2.Secondary Outcome
Title Percent Change From Baseline to Week 52 in Urinary Keratan Sulfate Measures
Hide Description Percent Change from Baseline to Week 52 for Urinary Keratan Sulfate measures.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set - All enrolled patients with at least 1 post treatment efficacy measurement will be included in efficacy analyses.
Arm/Group Title BMN110 2.0 mg/kg/Week
Hide Arm/Group Description:
Weekly intravenous infusions of BMN 110 at a dose of 2.0 mg/kg for 52 consecutive weeks. Each infusion will be administered over a period of approximately 4 hours.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: percentage change
-44.3  (21.15)
3.Secondary Outcome
Title Change From Baseline in Normalized Growth Rate Z-Scores
Hide Description Changes in growth over time will be assessed using anthropometric measurements and radiographs of lower extremities. Z-scores are the normalized scores derived from the reference population mean and standard deviation (A positive change from baseline indicates that the population has moved closer to the reference population and represents a positive outcome).
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis set - All enrolled patients with at least 1 post treatment efficacy measurement will be included in efficacy analyses.
Arm/Group Title BMN110 2.0 mg/kg/Week
Hide Arm/Group Description:
Weekly intravenous infusions of BMN 110 at a dose of 2.0 mg/kg for 52 consecutive weeks. Each infusion will be administered over a period of approximately 4 hours.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: z-score
Baseline Number Analyzed 8 participants
-0.6  (0.64)
Change from Baseline to Week 52 Number Analyzed 8 participants
0.2  (1.04)
Time Frame 52 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title BMN110 2.0 mg/kg/Week
Hide Arm/Group Description BMN110 2.0 mg/kg/week
All-Cause Mortality
BMN110 2.0 mg/kg/Week
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
BMN110 2.0 mg/kg/Week
Affected / at Risk (%) # Events
Total   8/15 (53.33%)    
Congenital, familial and genetic disorders   
Developmental hip dysplasia  1  1/15 (6.67%)  1
Gastrointestinal disorders   
Vomiting  1  1/15 (6.67%)  1
General disorders   
Medical device complication  1  1/15 (6.67%)  1
Pyrexia  1  1/15 (6.67%)  1
Immune system disorders   
Hypersensitivity  1  1/15 (6.67%)  1
Infections and infestations   
Device related infection  1  1/15 (6.67%)  1
Lower respiratory tract infection  1  1/15 (6.67%)  1
Sepsis  1  1/15 (6.67%)  1
Skin infection  1  1/15 (6.67%)  1
Musculoskeletal and connective tissue disorders   
Joint instability  1  1/15 (6.67%)  1
Knee deformity  1  1/15 (6.67%)  1
Nervous system disorders   
Cerebrospinal fluid leakage  1  1/15 (6.67%)  1
Cervical cord compression  1  4/15 (26.67%)  4
Spinal cord oedema  1  1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders   
Tonsillar hypertrophy  1  3/15 (20.00%)  3
Vascular disorders   
Poor venous access  1  3/15 (20.00%)  3
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%
BMN110 2.0 mg/kg/Week
Affected / at Risk (%) # Events
Total   15/15 (100.00%)    
Blood and lymphatic system disorders   
Lymphadenopathy  1  1/15 (6.67%)  1
Cardiac disorders   
Tachycardia  1  4/15 (26.67%)  9
Congenital, familial and genetic disorders   
Developmental hip dysplasia  1  1/15 (6.67%)  1
Ear and labyrinth disorders   
Aural polyp  1  1/15 (6.67%)  1
Cerumen impaction  1  1/15 (6.67%)  1
Conductive deafness  1  1/15 (6.67%)  2
Deafness  1  2/15 (13.33%)  2
Deafness bilateral  1  1/15 (6.67%)  1
Ear haemorrhage  1  1/15 (6.67%)  1
Ear pain  1  3/15 (20.00%)  17
Hearing impaired  1  1/15 (6.67%)  1
Middle ear effusion  1  1/15 (6.67%)  1
Motion sickness  1  1/15 (6.67%)  1
Otorrhoea  1  2/15 (13.33%)  2
Eye disorders   
Amblyopia  1  1/15 (6.67%)  1
Astigmatism  1  1/15 (6.67%)  1
Conjunctivitis  1  4/15 (26.67%)  5
Conjunctivitis allergic  1  1/15 (6.67%)  3
Corneal opacity  1  3/15 (20.00%)  3
Eye discharge  1  1/15 (6.67%)  3
Eye pain  1  1/15 (6.67%)  1
Eye swelling  1  2/15 (13.33%)  2
Keratitis  1  1/15 (6.67%)  1
Trichiasis  1  1/15 (6.67%)  1
Gastrointestinal disorders   
Abdominal distension  1  2/15 (13.33%)  4
Abdominal pain  1  8/15 (53.33%)  14
Abdominal pain upper  1  5/15 (33.33%)  14
Colitis  1  1/15 (6.67%)  1
Constipation  1  2/15 (13.33%)  2
Dental caries  1  1/15 (6.67%)  1
Diarrhoea  1  11/15 (73.33%)  24
Dyspepsia  1  1/15 (6.67%)  1
Flatulence  1  1/15 (6.67%)  2
Gastritis  1  2/15 (13.33%)  3
Gingival pain  1  1/15 (6.67%)  2
Mouth ulceration  1  1/15 (6.67%)  2
Nausea  1  4/15 (26.67%)  5
Oral discomfort  1  1/15 (6.67%)  1
Oral disorder  1  1/15 (6.67%)  2
Retching  1  1/15 (6.67%)  2
Toothache  1  3/15 (20.00%)  3
Vomiting  1  13/15 (86.67%)  59
General disorders   
Catheter site extravasation  1  4/15 (26.67%)  6
Catheter site pain  1  1/15 (6.67%)  1
Catheter site related reaction  1  2/15 (13.33%)  2
Chest pain  1  1/15 (6.67%)  1
Chills  1  1/15 (6.67%)  1
Crepitations  1  1/15 (6.67%)  1
Device difficult to use  1  1/15 (6.67%)  1
Fatigue  1  4/15 (26.67%)  6
Gait disturbance  1  1/15 (6.67%)  1
Implant site haemorrhage  1  1/15 (6.67%)  1
Infusion site extravasation  1  2/15 (13.33%)  3
Injection site hypersensitivity  1  1/15 (6.67%)  1
Local swelling  1  1/15 (6.67%)  1
Malaise  1  3/15 (20.00%)  4
Mass  1  1/15 (6.67%)  1
Medical device complication  1  1/15 (6.67%)  1
Medical device pain  1  1/15 (6.67%)  1
Medical device site reaction  1  1/15 (6.67%)  2
Pain  1  3/15 (20.00%)  3
Pyrexia  1  15/15 (100.00%)  143
Hepatobiliary disorders   
Hepatic function abnormal  1  1/15 (6.67%)  2
Portal vein thrombosis  1  1/15 (6.67%)  1
Infections and infestations   
Acute sinusitis  1  1/15 (6.67%)  1
Acute tonsillitis  1  1/15 (6.67%)  1
Anal fungal infection  1  1/15 (6.67%)  1
Bronchitis  1  3/15 (20.00%)  7
Conjunctivitis infective  1  1/15 (6.67%)  1
Diarrhoea infectious  1  1/15 (6.67%)  1
Ear infection  1  3/15 (20.00%)  4
Exanthema subitum  1  1/15 (6.67%)  2
Fungal skin infection  1  1/15 (6.67%)  1
Gastroenteritis  1  2/15 (13.33%)  3
Gastroenteritis viral  1  1/15 (6.67%)  2
Gingival infection  1  1/15 (6.67%)  1
Hand-foot-and-mouth disease  1  1/15 (6.67%)  1
Herpes simplex  1  1/15 (6.67%)  2
Hordeolum  1  1/15 (6.67%)  1
Implant site infection  1  3/15 (20.00%)  3
Influenza  1  3/15 (20.00%)  3
Lower respiratory tract infection  1  2/15 (13.33%)  4
Molluscum contagiosum  1  1/15 (6.67%)  2
Nasopharyngitis  1  9/15 (60.00%)  25
Oral candidiasis  1  1/15 (6.67%)  1
Otitis externa  1  2/15 (13.33%)  2
Otitis media  1  5/15 (33.33%)  6
Otitis media acute  1  3/15 (20.00%)  6
Otitis media chronic  1  1/15 (6.67%)  1
Penile infection  1  1/15 (6.67%)  1
Pharyngitis  1  2/15 (13.33%)  3
Postoperative wound infection  1  1/15 (6.67%)  1
Rash pustular  1  1/15 (6.67%)  1
Rhinitis  1  9/15 (60.00%)  22
Skin infection  1  2/15 (13.33%)  2
Tonsillitis  1  1/15 (6.67%)  1
Tooth infection  1  1/15 (6.67%)  1
Upper respiratory tract infection  1  8/15 (53.33%)  52
Urinary tract infection  1  1/15 (6.67%)  2
Viral infection  1  2/15 (13.33%)  2
Viral rash  1  1/15 (6.67%)  1
Viral upper respiratory tract infection  1  5/15 (33.33%)  8
Injury, poisoning and procedural complications   
Contusion  1  5/15 (33.33%)  5
Eye contusion  1  1/15 (6.67%)  1
Fall  1  2/15 (13.33%)  2
Foot fracture  1  1/15 (6.67%)  1
Head injury  1  2/15 (13.33%)  3
Infusion related reaction  1  2/15 (13.33%)  3
Injury corneal  1  1/15 (6.67%)  1
Laceration  1  1/15 (6.67%)  2
Limb crushing injury  1  1/15 (6.67%)  1
Lip injury  1  1/15 (6.67%)  1
Postoperative fever  1  1/15 (6.67%)  1
Procedural pain  1  3/15 (20.00%)  3
Procedural vomiting  1  1/15 (6.67%)  1
Scar  1  1/15 (6.67%)  1
Spinal cord injury  1  1/15 (6.67%)  1
Thermal burn  1  1/15 (6.67%)  1
Investigations   
Aspartate aminotransferase increased  1  1/15 (6.67%)  1
Blood bicarbonate decreased  1  2/15 (13.33%)  2
Body temperature increased  1  3/15 (20.00%)  5
Breath sounds abnormal  1  1/15 (6.67%)  1
Heart rate increased  1  3/15 (20.00%)  11
Oxygen saturation decreased  1  1/15 (6.67%)  1
Respiratory rate increased  1  2/15 (13.33%)  10
Venous pressure decreased  1  2/15 (13.33%)  2
Metabolism and nutrition disorders   
Decreased appetite  1  2/15 (13.33%)  2
Musculoskeletal and connective tissue disorders   
Arthralgia  1  7/15 (46.67%)  15
Back pain  1  3/15 (20.00%)  3
Bone pain  1  1/15 (6.67%)  2
Joint swelling  1  1/15 (6.67%)  1
Limb discomfort  1  1/15 (6.67%)  1
Musculoskeletal stiffness  1  2/15 (13.33%)  2
Myalgia  1  2/15 (13.33%)  2
Neck pain  1  2/15 (13.33%)  2
Pain in extremity  1  5/15 (33.33%)  15
Spinal disorder  1  1/15 (6.67%)  1
Nervous system disorders   
Cerebral haematoma  1  1/15 (6.67%)  1
Dizziness  1  1/15 (6.67%)  1
Headache  1  5/15 (33.33%)  13
Hypoaesthesia  1  1/15 (6.67%)  2
Psychiatric disorders   
Agitation  1  2/15 (13.33%)  3
Renal and urinary disorders   
Dysuria  1  2/15 (13.33%)  2
Haematuria  1  1/15 (6.67%)  1
Pollakiuria  1  1/15 (6.67%)  1
Vesicoureteric reflux  1  1/15 (6.67%)  1
Reproductive system and breast disorders   
Balanoposthitis  1  1/15 (6.67%)  1
Oedema genital  1  1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders   
Adenoidal hypertrophy  1  1/15 (6.67%)  1
Allergic respiratory disease  1  1/15 (6.67%)  1
Asthma  1  1/15 (6.67%)  1
Cough  1  11/15 (73.33%)  39
Haemoptysis  1  1/15 (6.67%)  1
Increased upper airway secretion  1  1/15 (6.67%)  1
Laryngospasm  1  1/15 (6.67%)  1
Nasal congestion  1  6/15 (40.00%)  15
Nasal obstruction  1  1/15 (6.67%)  1
Oropharyngeal pain  1  4/15 (26.67%)  23
Rhinitis allergic  1  2/15 (13.33%)  2
Rhinorrhoea  1  8/15 (53.33%)  20
Sleep apnoea syndrome  1  1/15 (6.67%)  1
Sneezing  1  3/15 (20.00%)  5
Throat irritation  1  1/15 (6.67%)  2
Tonsillar hypertrophy  1  1/15 (6.67%)  1
Wheezing  1  1/15 (6.67%)  1
Skin and subcutaneous tissue disorders   
Blister  1  2/15 (13.33%)  3
Cold sweat  1  1/15 (6.67%)  1
Dermatitis allergic  1  2/15 (13.33%)  3
Dermatitis diaper  1  1/15 (6.67%)  1
Dry skin  1  2/15 (13.33%)  2
Eczema  1  4/15 (26.67%)  5
Erythema  1  3/15 (20.00%)  3
Petechiae  1  1/15 (6.67%)  1
Pruritus  1  4/15 (26.67%)  7
Rash  1  6/15 (40.00%)  9
Rash erythematous  1  1/15 (6.67%)  1
Rash papular  1  1/15 (6.67%)  1
Skin disorder  1  1/15 (6.67%)  1
Skin reaction  1  1/15 (6.67%)  1
Urticaria  1  4/15 (26.67%)  36
Surgical and medical procedures   
Catheter placement  1  1/15 (6.67%)  1
Central venous catheter removal  1  1/15 (6.67%)  1
Central venous catheterisation  1  2/15 (13.33%)  2
Dental care  1  1/15 (6.67%)  1
Ear tube insertion  1  1/15 (6.67%)  1
Ear tube removal  1  1/15 (6.67%)  1
Infusion  1  1/15 (6.67%)  1
Joint fluid drainage  1  1/15 (6.67%)  1
Orchidopexy  1  1/15 (6.67%)  1
Vascular disorders   
Flushing  1  3/15 (20.00%)  3
Hot flush  1  1/15 (6.67%)  1
Hyperaemia  1  1/15 (6.67%)  1
Hypotension  1  2/15 (13.33%)  2
Pallor  1  1/15 (6.67%)  1
Poor venous access  1  4/15 (26.67%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Peter Slasor/Sr Director, Biostatistics, Global Clinical Sciences
Organization: BioMarin Pharmaceutical Inc.
Phone: 415-506-6765
EMail: PSlasor@bmrn.com
Layout table for additonal information
Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01515956     History of Changes
Other Study ID Numbers: MOR-007
First Submitted: December 22, 2011
First Posted: January 24, 2012
Results First Submitted: April 13, 2017
Results First Posted: July 6, 2017
Last Update Posted: August 10, 2017