Study of rhASB in Patients With Mucopolysaccharidosis VI

• Sponsor: BioMarin Pharmaceutical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00104234
• Collaborator: (none)
• Enrollment: 39
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long-term efficacy and safety of rhASB treatment in patients with Mucopolysaccharidosis VI.

Condition or Disease	Intervention/Treatment	Phase
Mucopolysaccharidosis VI	Drug: N-acetylgalactosamine 4-sulfatase; Drug: Placebo/rhASB	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Multinational Open-Label Extension Study of Recombinant Human N-acetylgalactosamine 4-sulfatase (rhASB) in Patients With Mucopolysaccharidosis VI
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Oct 1, 2006
• Actual Study Completion Date: Oct 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Other: rhASB/rhASB N-acetylgalactosamine 4-sulfatase	Drug: N-acetylgalactosamine 4-sulfatase; Other Names: rhASB
Other: Placebo/rhASB	Drug: Placebo/rhASB

Outcome Measures

Primary Outcome Measures

1. 12-Minute Walk Test [Baseline of ASB-03-05 through week 96 of ASB-03-06]

   Mean change in meters walked in 12 minutes. Mean change is the mean difference between the 12-Minute Walk Test at 96 weeks and that measured before first ever treatment with rhASB. For the rhASB/rhASB group, mean change is calculated for Week 96 - Baseline. For the placebo/rhASB group, mean change is calculated for Week 96 - Week 24.

Secondary Outcome Measures

1. 3-Minute Stair Climb [Baseline ASB-03-05 through week 96 of ASB-03-06.]

   Mean change in number of stairs climbed per minute in 3 minutes. Mean change is the mean difference between the 3-Minute Stair Climb at 96 weeks and that measured before first ever treatment with rhASB. Mean change is calculated for Week 96 - Baseline for the rhASB/rhASB group and for Week 96 - Week 24 for the placebo/rhASB group.

2. Change in Urinary Glycosaminoglycans (GAG) Level [72 weeks]

   Mean change in urinary GAG level for the first 72 weeks of rhASB treatment. For the rhASB/rhASB group, mean change was calculated for Week 72 -Baseline. For the placebo/rhASB, mean change was calculated for Week 96 - Week 24.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient consent

• Patient must have successfully completed study ASB-03-05, including having received at least 20 of 24 scheduled weekly infusions and having missed no more then two consecutive infusions

• If female of childbearing potential, patient must have a negative pregnancy test

Exclusion Criteria:

• Pregnant or lactating patient

• Patient has received an investigational drug within 30 days prior to study enrollment

• Patient is unwilling or unable to travel to the primary site for periodic assessments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BioMarin Pharmaceutical Inc.	Novato	California	United States	94949

Sponsors and Collaborators

• BioMarin Pharmaceutical

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00104234
• Other Study ID Numbers: ASB-03-06
• First Posted: Feb 25, 2005
• Last Update Posted: Feb 2, 2010
• Last Verified: Jan 1, 2010

• Additional relevant MeSH terms: Mucopolysaccharidoses; Mucopolysaccharidosis VI

Study Results

Participant Flow

Recruitment Details	Global study sites were hospitals and medical clinics. First Enrollment: 05FEB04 Last Dose: 28SEP06

Arm/Group Title	rhASB/rhASB	Placebo/rhASB
Arm/Group Description	Patients received rhASB in the double-blind study(ASB-03-05, NCT00067470)and continued to receive rhASB in the extension study(ASB-03-06).	Patients received placebo in the double-blind study (ASB-03-05, NCT00067470)then received rhASB in the extension study (ASB-03-06).
Period Title: Overall Study
STARTED	19	20
COMPLETED	19	19
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	rhASB/rhASB	Placebo/rhASB	Total
Arm/Group Description	Patients received rhASB in the double-blind study(ASB-03-05, NCT00067470)and continued to receive rhASB in the extension study(ASB-03-06).	Patients received placebo in the double-blind study (ASB-03-05, NCT00067470)then received rhASB in the extension study (ASB-03-06).	Total of all reporting groups
Overall Participants	19	20	39
Age (years) [Mean (Standard Deviation) ]
Age	13.7 (6.47)	10.7 (4.35)	12.2 (5.62)
Sex: Female, Male (Count of Participants)
Female	12 63.2%	14 70%	26 66.7%
Male	7 36.8%	6 30%	13 33.3%
Race/Ethnicity, Customized (participants) [Number]
White, non-Hispanic	15 78.9%	9 45%	24 61.5%
Hispanic	1 5.3%	3 15%	4 10.3%
Black	1 5.3%	2 10%	3 7.7%
Asian	1 5.3%	1 5%	2 5.1%
Indigenous	1 5.3%	1 5%	2 5.1%
Other	0 0%	4 20%	4 10.3%
Region of Enrollment (participants) [Number]
United States	2 10.5%	4 20%	6 15.4%
Germany	4 21.1%	4 20%	8 20.5%
United Kingdom	3 15.8%	3 15%	6 15.4%
Brazil	4 21.1%	4 20%	8 20.5%
France	2 10.5%	3 15%	5 12.8%
Portugal	4 21.1%	2 10%	6 15.4%

Outcome Measures

1. Primary Outcome

Title	12-Minute Walk Test
Description	Mean change in meters walked in 12 minutes. Mean change is the mean difference between the 12-Minute Walk Test at 96 weeks and that measured before first ever treatment with rhASB. For the rhASB/rhASB group, mean change is calculated for Week 96 - Baseline. For the placebo/rhASB group, mean change is calculated for Week 96 - Week 24.
Time Frame	Baseline of ASB-03-05 through week 96 of ASB-03-06

Outcome Measure Data

Analysis Population Description

The efficacy analysis included all subjects who continued in the extension study (ASB-03-06) except the 1 subject from the rhASB/rhASB group and 1 subject from the placebo/rhASB group who missed the Week 96 measurement.

Arm/Group Title	rhASB/rhASB	Placebo/rhASB
Arm/Group Description	Patients received rhASB in the double-blind study(ASB-03-05, NCT00067470)and continued to receive rhASB in the extension study(ASB-03-06).	Patients received placebo in the double-blind study (ASB-03-05, NCT00067470)then received rhASB in the extension study (ASB-03-06).
Measure Participants	18	18
Mean (Standard Deviation) [meters]	187 (187)	118 (127)

2. Secondary Outcome

Title	3-Minute Stair Climb
Description	Mean change in number of stairs climbed per minute in 3 minutes. Mean change is the mean difference between the 3-Minute Stair Climb at 96 weeks and that measured before first ever treatment with rhASB. Mean change is calculated for Week 96 - Baseline for the rhASB/rhASB group and for Week 96 - Week 24 for the placebo/rhASB group.
Time Frame	Baseline ASB-03-05 through week 96 of ASB-03-06.

Outcome Measure Data

Analysis Population Description

The efficacy analysis included all subjects who continued in the extension study (ASB-03-06) except 1 subject from the placebo/rhASB group who missed the Week 96 measurement.

Arm/Group Title	rhASB/rhASB	Placebo/rhASB
Arm/Group Description	Patients received rhASB in the double-blind study(ASB-03-05, NCT00067470)and continued to receive rhASB in the extension study(ASB-03-06).	Patients received placebo in the double-blind study (ASB-03-05, NCT00067470)then received rhASB in the extension study (ASB-03-06).
Measure Participants	19	18
Mean (Standard Deviation) [stairs/min]	13.1 (16.1)	11.1 (10.0)

3. Secondary Outcome

Title	Change in Urinary Glycosaminoglycans (GAG) Level
Description	Mean change in urinary GAG level for the first 72 weeks of rhASB treatment. For the rhASB/rhASB group, mean change was calculated for Week 72 -Baseline. For the placebo/rhASB, mean change was calculated for Week 96 - Week 24.
Time Frame	72 weeks

Outcome Measure Data

Analysis Population Description

rhASB/rhASB and placebo/rhASB groups were combined for the analysis, representing 72 weeks of rhASB treatment in each group.

Arm/Group Title	All Participants (N=37)
Arm/Group Description	rhASB/rhASB and placebo/rhASB groups were combined for analysis.
Measure Participants	37
Mean (Standard Deviation) [microgram/mg creatinine]	-231 (91)

Adverse Events

Arm/Group Title	All Participants
Arm/Group Description	rhASB/rhASB and placebo/rhASB groups were combined for analysis.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	14/38 (36.8%)
Cardiac disorders
Cardiac failure	2/38 (5.3%)	2
Mitral valve stenosis	1/38 (2.6%)	1
Congenital, familial and genetic disorders
Hip Dysplasia	1/38 (2.6%)	1
Ear and labyrinth disorders
Vertigo	1/38 (2.6%)	1
Gastrointestinal disorders
Inguinal hernia	1/38 (2.6%)	1
Inguinal hernia obstructive	1/38 (2.6%)	1
General disorders
Cyst	1/38 (2.6%)	1
Infections and infestations
Corneal Abscess	1/38 (2.6%)	1
Mastoiditis	1/38 (2.6%)	1
Pneumonia	2/38 (5.3%)	2
Staphylococcal sepsis	1/38 (2.6%)	1
Investigations
Body increased temperature	1/38 (2.6%)	1
Intraocular pressure increased	1/38 (2.6%)	1
Nervous system disorders
Cervical cord compression	1/38 (2.6%)	1
Cervical myelopathy	2/38 (5.3%)	2
Convulsion	1/38 (2.6%)	1
Dizziness	1/38 (2.6%)	1
Intracranial pressure increased	1/38 (2.6%)	1
Spinal cord compression	1/38 (2.6%)	1
Tension headache	1/38 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Broncopneumopathy	5/38 (13.2%)	5
Cough	1/38 (2.6%)	1
Pneumonitis	1/38 (2.6%)	1
Respiratory distress	2/38 (5.3%)	2
Tracheal stenosis	1/38 (2.6%)	1
Surgical and medical procedures
Hip surgery	1/38 (2.6%)	1
Osteotomy	1/38 (2.6%)	1
Vascular disorders
Haemorrhage	2/38 (5.3%)	2
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	38/38 (100%)
Blood and lymphatic system disorders
Anaemia	3/38 (7.9%)	3
Leukopenia	2/38 (5.3%)	2
Cardiac disorders
Cardiac valve disease	5/38 (13.2%)	5
Atrial hypertrophy	2/38 (5.3%)	2
Cardiac failure	2/38 (5.3%)	2
Cyanosis	2/38 (5.3%)	2
Dilatation atrial	2/38 (5.3%)	2
Ear and labyrinth disorders
Ear pain	13/38 (34.2%)	13
Hypoacusis	7/38 (18.4%)	7
Otorrhoea	7/38 (18.4%)	7
Cerumen impaction	3/38 (7.9%)	3
Eye disorders
Conjunctivitis	7/38 (18.4%)	7
Eye irritation	4/38 (10.5%)	4
Eye pain	4/38 (10.5%)	4
Eye redness	4/38 (10.5%)	4
Visual acuity reduced	4/38 (10.5%)	4
Eyelid oedema	2/38 (5.3%)	2
Glaucoma	2/38 (5.3%)	2
Keratoconjunctivitis sicca	2/38 (5.3%)	2
Gastrointestinal disorders
Diarrhoea	21/38 (55.3%)	21
Vomiting	18/38 (47.4%)	18
Abdominal pain	15/38 (39.5%)	15
Nausea	11/38 (28.9%)	11
Abdominal pain upper	7/38 (18.4%)	7
Constipation	6/38 (15.8%)	6
Toothache	4/38 (10.5%)	4
Dyspepsia	3/38 (7.9%)	3
Abdominal distension	2/38 (5.3%)	2
Inguinal hernia	2/38 (5.3%)	2
Mouth ulceration	2/38 (5.3%)	2
Stomatitis	2/38 (5.3%)	2
General disorders
Pyrexia	24/38 (63.2%)	24
Fatigue	8/38 (21.1%)	8
Influenza like illness	8/38 (21.1%)	8
Chest pain	7/38 (18.4%)	7
Pain	4/38 (10.5%)	4
Hernia pain	3/38 (7.9%)	3
Infusion site pain	3/38 (7.9%)	3
Oedema peripheral	3/38 (7.9%)	3
Rigors	3/38 (7.9%)	3
Hepatobiliary disorders
Hepatomegaly	2/38 (5.3%)	2
Infections and infestations
Ear infection	17/38 (44.7%)	17
Nasopharyngitis	16/38 (42.1%)	16
Upper respiratory tract infection	15/38 (39.5%)	15
Gastroenteritis	12/38 (31.6%)	12
Bronchitis	9/38 (23.7%)	9
Otitis externa	8/38 (21.1%)	8
Influenza	7/38 (18.4%)	7
Otitis media acute	7/38 (18.4%)	7
Sinusitis	6/38 (15.8%)	6
Hordeolum	5/38 (13.2%)	5
Pharyngitis	5/38 (13.2%)	5
Laryngitis	4/38 (10.5%)	4
Pneumonia	4/38 (10.5%)	4
Dental Caries	3/38 (7.9%)	3
Respiratory tract infection	3/38 (7.9%)	3
Tinea pedis	3/38 (7.9%)	3
Otitis media	6/38 (15.8%)	6
Varicella	3/38 (7.9%)	3
Bronchopneumonia	2/38 (5.3%)	2
Folliculitis	2/38 (5.3%)	2
Fungal infection	2/38 (5.3%)	2
Furuncle	2/38 (5.3%)	2
Lower respiratory tract infection	2/38 (5.3%)	2
Subcutaneous abscess	2/38 (5.3%)	2
Tonsillitis	2/38 (5.3%)	2
Tooth abscess	2/38 (5.3%)	2
Injury, poisoning and procedural complications
Post procedural pain	10/38 (26.3%)	10
Head injury	4/38 (10.5%)	4
Procedural site reaction	3/38 (7.9%)	3
Excoriation	2/38 (5.3%)	2
Fall	2/38 (5.3%)	2
Joint injury	2/38 (5.3%)	2
Investigations
Neutrophil count increased	3/38 (7.9%)	3
QRS axis abnormal	3/38 (7.9%)	3
Blood alkaline phosphatase increased	2/38 (5.3%)	2
Cardiac murmur	2/38 (5.3%)	2
Oxygen saturation decreased	2/38 (5.3%)	2
Metabolism and nutrition disorders
Hypokalaemia	3/38 (7.9%)	3
Iron deficiency	2/38 (5.3%)	2
Musculoskeletal and connective tissue disorders
Athralgia	19/38 (50%)	19
Pain in extremity	18/38 (47.4%)	18
Back pain	15/38 (39.5%)	15
Bone pain	4/38 (10.5%)	4
Joint stiffness	4/38 (10.5%)	4
Myalgia	4/38 (10.5%)	4
Hip deformity	3/38 (7.9%)	3
Groin pain	2/38 (5.3%)	2
Intervertibral disc disorder	2/38 (5.3%)	2
Joint contracture	2/38 (5.3%)	2
Kyphoscoliosis	2/38 (5.3%)	2
Neck pain	2/38 (5.3%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Papilloma	2/38 (5.3%)	2
Nervous system disorders
Headache	27/38 (71.1%)	27
Dizziness	5/38 (13.2%)	5
Paraesthesia	4/38 (10.5%)	4
Hyperreflexia	3/38 (7.9%)	3
Hypoaesthenia	3/38 (7.9%)	3
Tremor	3/38 (7.9%)	3
Cervical myelopathy	2/38 (5.3%)	2
Migrane	2/38 (5.3%)	2
Somnolence	2/38 (5.3%)	2
Psychiatric disorders
Abnormal behavior	2/38 (5.3%)	2
Anxiety	2/38 (5.3%)	2
Renal and urinary disorders
Dysuria	3/38 (7.9%)	3
Respiratory, thoracic and mediastinal disorders
Cough	28/38 (73.7%)	28
Pharyngolaryngeal pain	13/38 (34.2%)	13
Rhinorrhoea	8/38 (21.1%)	8
Bronchospasm	7/38 (18.4%)	7
Dyspnoea	6/38 (15.8%)	6
Nasal congestion	6/38 (15.8%)	6
Pulmonary hypertention	5/38 (13.2%)	5
Rhinitis	4/38 (10.5%)	4
Wheezing	4/38 (10.5%)	4
Asthma	3/38 (7.9%)	3
Restrictive pulmonary disease	3/38 (7.9%)	3
Apnoea	2/38 (5.3%)	2
Chest pain	2/38 (5.3%)	2
Epistaxis	2/38 (5.3%)	2
Increased bronchial secretion	2/38 (5.3%)	2
Oropharyngeal swelling	2/38 (5.3%)	2
Tachypnoea	2/38 (5.3%)	2
Upper respiratory tract congestion	2/38 (5.3%)	2
Skin and subcutaneous tissue disorders
Pruritus	8/38 (21.1%)	8
Rash papular	7/38 (18.4%)	7
Rash	5/38 (13.2%)	5
Urticaria	4/38 (10.5%)	4
Erythema	3/38 (7.9%)	3
Prurigo	3/38 (7.9%)	3
Acne	2/38 (5.3%)	2
Eczema	2/38 (5.3%)	2
Exanthem	2/38 (5.3%)	2
Face oedema	2/38 (5.3%)	2
Pityriasis rosea	2/38 (5.3%)	2
Rash erythematous	2/38 (5.3%)	2
Surgical and medical procedures
Tooth extraction	2/38 (5.3%)	2
Vascular disorders
Hypotension	4/38 (10.5%)	4
Poor venous access	4/38 (10.5%)	4
Haematoma	2/38 (5.3%)	2
Hyperaemia	2/38 (5.3%)	2
Hypertension	2/38 (5.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first publication of the results shall be made by Sponsor in a joint publication. If such a multicenter publication is not submitted within 12 months after conclusion of the study, the PI may publish the results from their site individually, subject however to comply with the other terms of the agreement.