A Phase 4 Two Dose Level Study of Naglazyme(TM) (Galsulfase) in Infants With MPS VI

• Sponsor: BioMarin Pharmaceutical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00299000
• Collaborator: (none)
• Enrollment: 4
• Locations: 4
• Arms: 2
• Duration (Months): 35
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety and efficacy of two dose levels of Naglazyme in infants under the age of one year who have MPS VI by monitoring physical appearance, x-ray of the skeletal system and growth.

Condition or Disease	Intervention/Treatment	Phase
Mucopolysaccharidosis VI; Maroteaux-Lamy Syndrome	Drug: Naglazyme	Phase 4

Detailed Description

The primary objective of the study was to evaluate the efficacy of two dose levels of Naglazyme in preventing the progression of skeletal dysplasia in infants under the age of one year who have MPS VI by monitoring physical appearance, x-ray of the skeletal system and growth.

The secondary objective of the study was to evaluate the efficacy of the two dose levels of Naglazyme in preventing several measures of disease progression in infants under the age of one year who have MPS VI by monitoring urinary GAGs, gross and fine motor function, cardiac function, vision, hearing, and use of health resources.

The safety objective of the study was to evaluate the safety of two dose levels of Naglazyme in infants under the age of one year who have MPS VI.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 4 Multi-center, Multi-national, Open-label, Randomized, Two Dose Level Study of Naglazyme(TM) (Galsulfase) in Infants With Maroteaux-Lamy Syndrome (MPS VI)
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Naglazyme, 1.0 mg/kg Dose comparison	Drug: Naglazyme; Weekly infusion for minimum of 52 weeks. Naglazyme is diluted in sterile 0.9% sodium chloride solution; Other Names: recombinant human N-acetylgalactosamine 4-sulfatase rh-arylsulfatase B rhASB
Other: Naglazyme, 2.0 mg/kg Dose Comparison	Drug: Naglazyme; Weekly infusion for minimum of 52 weeks. Naglazyme is diluted in sterile 0.9% sodium chloride solution; Other Names: recombinant human N-acetylgalactosamine 4-sulfatase rh-arylsulfatase B rhASB

Outcome Measures

Primary Outcome Measures

1. Change in Height [52 weeks]

2. Change in Weight [52 weeks]

3. Change in Haed Circumference [52 weeks]

Secondary Outcome Measures

1. Change in Urinary Glycosaminoglycan Levels [minimum 52 weeks of dosing]

   Change in urinary GAG levels was calculated from baseline to week 52 of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 1 Year
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent by a parent or legal guardian

• Parent or legal guardian willing and able to comply with all study procedures

• Equal to or greater than 36 weeks estimated gestational age by physical exam at birth

• Has a diagnosis of MPS VI based on a documented prenatal diagnosis or fibroblast or leukocyte N-acetylgalactosamine 4-sulfatase (ASB) enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory

• Is less than one year of age

• Has no evidence of skeletal dysplasia based on physical exam

Exclusion Criteria:

• Parent of legal guardian perceived to be unreliable or unavailable for study participation

• Use of any investigational drug within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments

• Has concurrent disease or condition that would interfere with study participation or safety (i.e., has previously undergone hematopoietic stem cell transplantation such as bone marrow or cord blood transplantation, or major organ transplantation)

• Any condition that, in the view of the principle investigator, renders the subject at high risk from treatment compliance and/or completing the study

• Has known hypersensitivity to Naglazyme

• Has previously received Naglazyme

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	Children's Hospital Oakland	Oakland	California	United States	94609
3	Hospital Femme Mere Enfant Centre	Lyon		France	69677
4	Hospital PediAtrico de Coimbra	Coimbra		Portugal	3000-076

Sponsors and Collaborators

• BioMarin Pharmaceutical

Investigators

• Study Director: Celeste Decker, MD, BioMarin Pharmaceutical

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BioMarin Pharmaceutical Inc Website

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00299000
• Other Study ID Numbers: ASB-008
• First Posted: Mar 6, 2006
• Last Update Posted: Jul 22, 2011
• Last Verified: Jul 1, 2011

• Additional relevant MeSH terms: Mucopolysaccharidoses; Mucopolysaccharidosis VI; Syndrome

Study Results

Participant Flow

Recruitment Details	Global study sites were hospitals. First Enrollment: 08MAY2006 Last Dose: 30APR2009

Arm/Group Title	Naglazyme, 1.0 mg/kg	Naglazyme, 2.0 mg/kg
Arm/Group Description	weekly infusions for minimum of 52 weeks	weekly infusions for minimum of 52 weeks
Period Title: Overall Study
STARTED	2	2
COMPLETED	2	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Naglazyme, 1.0 mg/kg	Naglazyme, 2.0 mg/kg	Total
Arm/Group Description	weekly infusions for minimum of 52 weeks	weekly infusions for minimum of 52 weeks	Total of all reporting groups
Overall Participants	2	2	4
Age (Count of Participants)
<=18 years	2 100%	2 100%	4 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	6.05 (3.89)	12.4 (0.42)	9.23 (4.31)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	2 100%	2 100%	4 100%
Race/Ethnicity, Customized (participants) [Number]
White, non-Hispanic	1 50%	1 50%	2 50%
Hispanic/Latino	1 50%	0 0%	1 25%
Other	0 0%	1 50%	1 25%
Region of Enrollment (participants) [Number]
United States	2 100%	0 0%	2 50%
France	0 0%	1 50%	1 25%
Portugal	0 0%	1 50%	1 25%

Outcome Measures

1. Secondary Outcome

Title	Change in Urinary Glycosaminoglycan Levels
Description	Change in urinary GAG levels was calculated from baseline to week 52 of treatment.
Time Frame	minimum 52 weeks of dosing

Outcome Measure Data

Analysis Population Description

Intention to treat.

Arm/Group Title	Naglazyme, 1.0 mg/kg	Naglazyme, 2.0 mg/kg
Arm/Group Description	weekly infusions for minimum of 52 weeks	weekly infusions for minimum of 52 weeks
Measure Participants	2	2
Baseline	1041.87 (86.32)	698.95 (142.34)
Week 52	261.15 (54.38)	178.10 (42.43)
Change from Baseline to Week 52	-780.72 (140.69)	-520.85 (99.91)

2. Primary Outcome

Title	Change in Height
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat.

Arm/Group Title	Naglazyme, 1.0 mg/kg	Naglazyme, 2.0 mg/kg
Arm/Group Description	weekly infusions for minimum of 52 weeks	weekly infusions for minimum of 52 weeks
Measure Participants	2	2
Height at baseline	67.3 (5.1)	80.3 (1.8)
Height at week 52	81.9 (1.8)	91.3 (5.2)
Change in height	14.6 (6.9)	11.0 (7.0)

3. Primary Outcome

Title	Change in Weight
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naglazyme, 1.0 mg/kg	Naglazyme, 2.0 mg/kg
Arm/Group Description	weekly infusions for minimum of 52 weeks	weekly infusions for minimum of 52 weeks
Measure Participants	2	2
weight at baseline	7.1 (.3)	10.2 (.6)
weight at week 52	11.3 (.3)	13.3 (1.0)
change in weight	4.2 (.6)	3.1 (1.6)

4. Primary Outcome

Title	Change in Haed Circumference
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naglazyme, 1.0 mg/kg	Naglazyme, 2.0 mg/kg
Arm/Group Description	weekly infusions for minimum of 52 weeks	weekly infusions for minimum of 52 weeks
Measure Participants	2	2
head circumference at baseline	43.5 (3.0)	49.1 (.5)
head circumference at 52 weeks	48.5 (1.0)	51.8 (.8)
Change in head circumference	5.0 (4.0)	2.7 (1.3)

Adverse Events

Time Frame	All patients received weekly infusions of Nagalzyme for a minimum of 52 weeks. The range in time of exposure to Naglazyme for the duration of the study was 52.9 to 153.30 weeks.
Arm/Group Title	Naglazyme, 1.0 mg/kg		Naglazyme, 2.0 mg/kg
Arm/Group Description	weekly infusions for minimum of 52 weeks		weekly infusions for minimum of 52 weeks
All Cause Mortality
	Naglazyme, 1.0 mg/kg		Naglazyme, 2.0 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Naglazyme, 1.0 mg/kg		Naglazyme, 2.0 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		2/2 (100%)
Gastrointestinal disorders
Umbilical hernia	0/2 (0%)	0	1/2 (50%)	1
Infections and infestations
Pneumonia	1/2 (50%)	1	0/2 (0%)	0
Tonsillitis	0/2 (0%)	0	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
Scoliosis	0/2 (0%)	0	1/2 (50%)	3
Nervous system disorders
Febrile convulsion	0/2 (0%)	0	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy	0/2 (0%)	0	1/2 (50%)	2
Respiratory distress	1/2 (50%)	1	0/2 (0%)	0
Surgical and medical procedures
Cast application	0/2 (0%)	0	1/2 (50%)	1
Vascular disorders
Poor venous access	1/2 (50%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Naglazyme, 1.0 mg/kg		Naglazyme, 2.0 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		2/2 (100%)
Gastrointestinal disorders
Diarrhea	2/2 (100%)	4	2/2 (100%)	3
Umbilical hernia	2/2 (100%)	3	1/2 (50%)	1
Vomiting	1/2 (50%)	2	2/2 (100%)	3
General disorders
Pyrexia	2/2 (100%)	8	1/2 (50%)	31
Infections and infestations
Ear infection	2/2 (100%)	2	2/2 (100%)	4
Rhinitis	1/2 (50%)	3	2/2 (100%)	3
Upper respiratory tract infections	2/2 (100%)	9	1/2 (50%)	3
Respiratory, thoracic and mediastinal disorders
Nasal congestion	2/2 (100%)	15	1/2 (50%)	1

Limitations/Caveats

Given the small number of patients (4) represented in this study, the outcomes observed in this study may not reflect or predict outcomes observed by physicians in clinical practice.

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 the 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 site individually, subject however to comply with the other terms of the agreement.