A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

• Sponsor: BioMarin Pharmaceutical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01275066
• Collaborator: (none)
• Enrollment: 177
• Locations: 28
• Arms: 3
• Duration (Months): 18
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This Phase 3 study will evaluate the efficacy and safety of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).

There is currently no standard accepted treatment for MPS IVA other than supportive care. Enzyme replacement therapy (ERT) may be a potential new treatment option for MPS IVA patients. BMN 110 is administered to MPS IVA patients by IV infusion, allowing cellular uptake by the mannose-6-phosphate receptor and transportation to the lysosomes.

This enzyme uptake into the lysosomes is hypothesized to promote increased catabolism of keratan sulfate (KS) in tissue macrophages, hyaline cartilage, other connective tissues, and heart valve, and reduce the progressive accumulation of KS which is responsible for the clinical manifestations of the disorders.

Condition or Disease	Intervention/Treatment	Phase
MPS IV A	Drug: BMN 110 Weekly; Drug: Placebo; Drug: BMN 110 Every Other Week	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 177 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multinational Clinical Study to Evaluate the Efficacy and Safety of 2.0 mg/kg/Week and 2.0 mg/kg/Every Other Week BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.
Experimental: BMN 110 Weekly	Drug: BMN 110 Weekly; BMN 110 Weekly: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.; Other Names: recombinant human N-acetylgalactosamine-6-sulfatase rhGALNS
Experimental: BMN 110 Every Other Week	Drug: BMN 110 Every Other Week; BMN 110 Every Other Week: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.; Other Names: recombinant human N-acetylgalactosamine-6-sulfatase rhGALNS

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Endurance as Measured by the 6-minute Walk Test [Baseline to Week 24]

Secondary Outcome Measures

1. Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test [Baseline to Week 24]

2. Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine [Baseline to Week 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least 5 years of age.

• Documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA.

• Willing and able to provide written, signed informed consent, or in the case of patients under the age of 18 (or 16 years, depending on the region), provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.

• Must meet the study entrance requirements for the 6-minute walk test.

• Sexually active patients must be willing to use an acceptable method of contraception while participating in the study.

• Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study.

Exclusion Criteria:

• Previous hematopoietic stem cell transplant (HSCT).

• Previous treatment with BMN 110.

• Has known hypersensitivity to any of the components of BMN 110.

• Major surgery within 3 months prior to study entry or planned major surgery during the 24-week treatment period.

• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.

• Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.

• Concurrent disease or condition, including but not limited to symptomatic cervical spine instability, clinically significant spinal cord compression, or severe cardiac disease that would interfere with study participation or safety as determined by the Investigator.

• Any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Oakland	California	United States
2		Wilmington	Delaware	United States
3		Washington	District of Columbia	United States
4		Chicago	Illinois	United States
5		New York	New York	United States
6		Seattle	Washington	United States
7		Cordoba		Argentina
8		Campina Grande		Brazil
9		Porto Alegre		Brazil
10		Montreal		Canada
11		Sherbrooke		Canada
12		Toronto		Canada
13		Bogota		Colombia
14		Copenhagen		Denmark
15		Lyon		France
16		Paris		France
17		Mainz		Germany
18		Monza		Italy
19		Tokyo		Japan
20		Seoul		Korea, Republic of
21		Amsterdam		Netherlands
22		Coimbra		Portugal
23		Doha		Qatar
24		Riyadh		Saudi Arabia
25		Taipei		Taiwan
26		Birmingham		United Kingdom
27		London		United Kingdom
28		Manchester		United Kingdom

Sponsors and Collaborators

• BioMarin Pharmaceutical

Investigators

• Study Director: Debra Lounsbury, BioMarin Pharmaceutical

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BioMarin Pharmaceutical Inc. website
• The BioMarin Morquio Program

Publications

None provided.

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT01275066
• Other Study ID Numbers: MOR-004; 2010-020198-18; 10/H1306/87; 18972/0213/001-0001; 2011_038#B201129; 145240; 2011-01-09; 20110012889; 0999935174
• First Posted: Jan 12, 2011
• Last Update Posted: Jul 7, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by BioMarin Pharmaceutical: Mucopolysaccharidosis IV type A; MPS IV Type A; Mucopolysaccharidosis IVA; MPS IVA; Morquio A Syndrome; Lysosomal Storage Disorder; LSD; N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy; ERT
• Additional relevant MeSH terms: Mucopolysaccharidoses

Study Results

Participant Flow

Arm/Group Title	Placebo	BMN110 2.0 mg/kg/Qow	BMN110 2.0 mg/kg/Week
Arm/Group Description	Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
Period Title: Overall Study
STARTED	60	59	58
Treated	59	59	58
COMPLETED	59	59	57
NOT COMPLETED	1	0	1

Baseline Characteristics

Arm/Group Title	Placebo	BMN110 2.0 mg/kg/Qow	BMN110 2.0 mg/kg/Week	Total
Arm/Group Description	Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.	Total of all reporting groups
Overall Participants	59	59	58	176
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.0 (11.30)	15.3 (10.79)	13.1 (8.10)	14.5 (10.16)
Age, Customized (participants) [Number]
5 - 11 years	30 50.8%	31 52.5%	32 55.2%	93 52.8%
12 - 18 years	15 25.4%	16 27.1%	16 27.6%	47 26.7%
>= 19 years	14 23.7%	12 20.3%	10 17.2%	36 20.5%
Sex: Female, Male (Count of Participants)
Female	32 54.2%	25 42.4%	32 55.2%	89 50.6%
Male	27 45.8%	34 57.6%	26 44.8%	87 49.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 22%	16 27.1%	9 15.5%	38 21.6%
Not Hispanic or Latino	46 78%	43 72.9%	49 84.5%	138 78.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	11 18.6%	15 25.4%	14 24.1%	40 22.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 3.4%	2 3.4%	4 2.3%
White	44 74.6%	35 59.3%	36 62.1%	115 65.3%
Other	4 6.8%	7 11.9%	6 10.3%	17 9.7%
Region of Enrollment (participants) [Number]
Argentina	1 1.7%	1 1.7%	0 0%	2 1.1%
Brazil	6 10.2%	10 16.9%	5 8.6%	21 11.9%
Canada	4 6.8%	5 8.5%	5 8.6%	14 8%
Colombia	2 3.4%	2 3.4%	2 3.4%	6 3.4%
Denmark	0 0%	0 0%	1 1.7%	1 0.6%
France	7 11.9%	5 8.5%	8 13.8%	20 11.4%
Germany	4 6.8%	5 8.5%	1 1.7%	10 5.7%
Italy	4 6.8%	4 6.8%	2 3.4%	10 5.7%
Japan	0 0%	4 6.8%	2 3.4%	6 3.4%
Korea, South	3 5.1%	1 1.7%	3 5.2%	7 4%
Netherlands	1 1.7%	2 3.4%	3 5.2%	6 3.4%
Portugal	2 3.4%	1 1.7%	0 0%	3 1.7%
Qatar	1 1.7%	0 0%	1 1.7%	2 1.1%
Saudi Arabia	2 3.4%	1 1.7%	4 6.9%	7 4%
Taiwan	1 1.7%	3 5.1%	1 1.7%	5 2.8%
United Kingdom	9 15.3%	4 6.8%	10 17.2%	23 13.1%
United States	12 20.3%	11 18.6%	10 17.2%	33 18.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Endurance as Measured by the 6-minute Walk Test
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Intention to treat (all patients receiving at least one dose of study drug). Two missing outcomes at Week 24 were imputed using method of multiple imputation.

Arm/Group Title	Placebo	BMN110 2.0 mg/kg/Qow	BMN110 2.0 mg/kg/Week
Arm/Group Description	Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
Measure Participants	59	59	58
Baseline	211.9 (69.88)	205.7 (81.19)	203.9 (76.32)
Week 24	225.4 (83.22)	219.9 (87.60)	240.0 (86.61)
Change from Baseline to Week 24	13.5 (50.63)	14.2 (40.82)	36.0 (58.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, BMN110 2.0 mg/kg/Week
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0174
	Comments	Hochberg multiplicity adjustment - results considered statistically significant if both of p-values are p<0.05 or either of p-values is p<0.025.
	Method	ANCOVA
	Comments	ANCOVA of change from baseline with treatment, age group, baseline 6MWT category as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	22.5
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.35
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, BMN110 2.0 mg/kg/Qow
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9542
	Comments	Hochberg multiplicity adjustment - results considered statistically significant if both of p-values are p<0.05 or either of p-values is p<0.025.
	Method	ANCOVA
	Comments	ANCOVA of change from baseline with treatment, age group, baseline 6MWT category as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.29
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Intention to treat (all patients receiving at least one dose of study drug). Two missing outcomes at Week 24 were imputed using method of multiple imputation.

Arm/Group Title	Placebo	BMN110 2.0 mg/kg/Qow	BMN110 2.0 mg/kg/Week
Arm/Group Description	Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
Measure Participants	59	59	58
Baseline	30.0 (14.05)	27.1 (15.80)	29.6 (16.44)
Week 24	33.6 (18.36)	30.4 (17.77)	34.3 (18.70)
Change from Baseline to Week 24	3.6 (8.51)	3.2 (10.29)	4.7 (7.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, BMN110 2.0 mg/kg/Week
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4935
	Comments	Hochberg multiplicity adjustment - results considered statistically significant if both of p-values are p<0.05 or either of p-values is p<0.025.
	Method	ANCOVA
	Comments	ANCOVA of change from baseline with treatment, age group, baseline 6MWT category, and baseline 3MSCT as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.1
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.66
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, BMN110 2.0 mg/kg/Qow
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7783
	Comments	Hochberg multiplicity adjustment - results considered statistically significant if both of p-values are p<0.05 or either of p-values is p<0.025.
	Method	ANCOVA
	Comments	ANCOVA of change from baseline with treatment, age group, baseline 6MWT category, and baseline 3MSCT as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.66
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Intention to treat (all patients receiving at least one dose of study drug). Nine missing outcomes at Week 24 were imputed using method of multiple imputation.

Arm/Group Title	Placebo	BMN110 2.0 mg/kg/Qow	BMN110 2.0 mg/kg/Week
Arm/Group Description	Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.	Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
Measure Participants	59	59	58
Mean (Standard Deviation) [percent change]	-3.6 (27.41)	-35.3 (20.74)	-43.7 (22.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, BMN110 2.0 mg/kg/Week
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Hochberg multiplicity adjustment - results considered statistically significant if both of p-values are p<0.05 or either of p-values is p<0.025.
	Method	ANCOVA
	Comments	ANCOVA of change from baseline with treatment, age group, baseline 6MWT category, and baseline uKS normalized for creatinine, as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-40.7
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.20
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, BMN110 2.0 mg/kg/Qow
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Hochberg multiplicity adjustment - results considered statistically significant if both of p-values are p<0.05 or either of p-values is p<0.025.
	Method	ANCOVA
	Comments	ANCOVA of change from baseline with treatment, age group, baseline 6MWT category, and baseline uKS normalized for creatinine, as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-30.2
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.19
	Estimation Comments

Adverse Events

Time Frame	Study Period, through 24 weeks
Adverse Event Reporting Description	Treatment Emergent Events Only
Arm/Group Title	Placebo		BMN110 2.0 mg/kg/Qow		BMN110 2.0 mg/kg/Week
Arm/Group Description	Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.		Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.		Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
All Cause Mortality
	Placebo		BMN110 2.0 mg/kg/Qow		BMN110 2.0 mg/kg/Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		BMN110 2.0 mg/kg/Qow		BMN110 2.0 mg/kg/Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/59 (3.4%)		4/59 (6.8%)		9/58 (15.5%)
Ear and labyrinth disorders
Deafness	1/59 (1.7%)	1	0/59 (0%)	0	0/58 (0%)	0
Gastrointestinal disorders
Vomiting	0/59 (0%)	0	0/59 (0%)	0	1/58 (1.7%)	1
General disorders
Infusion site pain	0/59 (0%)	0	0/59 (0%)	0	1/58 (1.7%)	1
Immune system disorders
Anaphylactic reaction	0/59 (0%)	0	1/59 (1.7%)	1	0/58 (0%)	0
Hypersensitivity	0/59 (0%)	0	0/59 (0%)	0	1/58 (1.7%)	1
Infections and infestations
Dengue fever	0/59 (0%)	0	1/59 (1.7%)	1	0/58 (0%)	0
Lower respiratory tract infection	0/59 (0%)	0	0/59 (0%)	0	1/58 (1.7%)	1
Otitis media	0/59 (0%)	0	1/59 (1.7%)	1	1/58 (1.7%)	1
Pneumonia	0/59 (0%)	0	0/59 (0%)	0	2/58 (3.4%)	2
Viral upper respiratory tract infection	0/59 (0%)	0	0/59 (0%)	0	1/58 (1.7%)	1
Nervous system disorders
Cervical cord compression	1/59 (1.7%)	1	0/59 (0%)	0	0/58 (0%)	0
Skin and subcutaneous tissue disorders
Urticaria	0/59 (0%)	0	0/59 (0%)	0	1/58 (1.7%)	1
Surgical and medical procedures
Suture removal	0/59 (0%)	0	1/59 (1.7%)	1	0/58 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		BMN110 2.0 mg/kg/Qow		BMN110 2.0 mg/kg/Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/59 (96.6%)		59/59 (100%)		56/58 (96.6%)
Cardiac disorders
Mitral valve incompetence	4/59 (6.8%)	4	3/59 (5.1%)	3	3/58 (5.2%)	3
Pulmonary valve incompetence	2/59 (3.4%)	2	1/59 (1.7%)	1	3/58 (5.2%)	3
Tachycardia	6/59 (10.2%)	7	2/59 (3.4%)	6	3/58 (5.2%)	8
Tricuspid valve incompetence	3/59 (5.1%)	3	7/59 (11.9%)	7	4/58 (6.9%)	4
Ear and labyrinth disorders
Ear pain	5/59 (8.5%)	6	8/59 (13.6%)	11	3/58 (5.2%)	3
Eye disorders
Corneal opacity	1/59 (1.7%)	1	0/59 (0%)	0	5/58 (8.6%)	5
Gastrointestinal disorders
Abdominal discomfort	1/59 (1.7%)	1	3/59 (5.1%)	4	2/58 (3.4%)	4
Abdominal pain	5/59 (8.5%)	5	8/59 (13.6%)	14	14/58 (24.1%)	23
Abdominal pain upper	5/59 (8.5%)	6	4/59 (6.8%)	4	9/58 (15.5%)	22
Diarrhoea	7/59 (11.9%)	8	12/59 (20.3%)	14	12/58 (20.7%)	14
Dyspepsia	4/59 (6.8%)	4	1/59 (1.7%)	1	1/58 (1.7%)	1
Flatulence	3/59 (5.1%)	4	1/59 (1.7%)	1	0/58 (0%)	0
Nausea	12/59 (20.3%)	13	14/59 (23.7%)	22	18/58 (31%)	37
Vomiting	21/59 (35.6%)	42	21/59 (35.6%)	44	25/58 (43.1%)	60
General disorders
Chest discomfort	0/59 (0%)	0	1/59 (1.7%)	1	3/58 (5.2%)	3
Chills	1/59 (1.7%)	1	6/59 (10.2%)	7	6/58 (10.3%)	7
Device occlusion	1/59 (1.7%)	1	2/59 (3.4%)	2	3/58 (5.2%)	4
Fatigue	15/59 (25.4%)	24	8/59 (13.6%)	10	9/58 (15.5%)	17
Infusion site extravasation	2/59 (3.4%)	2	4/59 (6.8%)	4	2/58 (3.4%)	2
Infusion site pain	0/59 (0%)	0	4/59 (6.8%)	7	3/58 (5.2%)	3
Non-cardiac chest pain	0/59 (0%)	0	3/59 (5.1%)	3	1/58 (1.7%)	1
Oedema peripheral	2/59 (3.4%)	2	4/59 (6.8%)	6	1/58 (1.7%)	1
Puncture site pain	2/59 (3.4%)	2	3/59 (5.1%)	3	1/58 (1.7%)	1
Pyrexia	17/59 (28.8%)	29	22/59 (37.3%)	35	25/58 (43.1%)	47
Immune system disorders
Hypersensitivity	1/59 (1.7%)	1	4/59 (6.8%)	7	2/58 (3.4%)	2
Infections and infestations
Ear infection	1/59 (1.7%)	1	2/59 (3.4%)	2	5/58 (8.6%)	5
Gastroenteritis	4/59 (6.8%)	4	8/59 (13.6%)	10	7/58 (12.1%)	8
Influenza	3/59 (5.1%)	4	5/59 (8.5%)	5	2/58 (3.4%)	3
Nasopharyngitis	9/59 (15.3%)	12	12/59 (20.3%)	13	10/58 (17.2%)	11
Otitis media	4/59 (6.8%)	4	5/59 (8.5%)	5	8/58 (13.8%)	9
Pharyngitis	7/59 (11.9%)	7	3/59 (5.1%)	3	4/58 (6.9%)	4
Rhinitis	6/59 (10.2%)	8	4/59 (6.8%)	8	5/58 (8.6%)	8
Upper respiratory tract infection	9/59 (15.3%)	14	10/59 (16.9%)	13	10/58 (17.2%)	15
Viral infection	1/59 (1.7%)	1	6/59 (10.2%)	6	3/58 (5.2%)	3
Viral upper respiratory tract infection	3/59 (5.1%)	5	4/59 (6.8%)	5	2/58 (3.4%)	3
Injury, poisoning and procedural complications
Fall	1/59 (1.7%)	1	4/59 (6.8%)	5	0/58 (0%)	0
Head injury	0/59 (0%)	0	3/59 (5.1%)	3	2/58 (3.4%)	2
Ligament sprain	3/59 (5.1%)	3	0/59 (0%)	0	0/58 (0%)	0
Investigations
Blood pressure diastolic increased	2/59 (3.4%)	5	3/59 (5.1%)	4	2/58 (3.4%)	2
Blood pressure systolic increased	2/59 (3.4%)	5	3/59 (5.1%)	16	1/58 (1.7%)	1
Body temperature increased	2/59 (3.4%)	10	2/59 (3.4%)	2	4/58 (6.9%)	24
Oxygen saturation decreased	6/59 (10.2%)	19	7/59 (11.9%)	8	6/58 (10.3%)	10
Respiratory rate increased	3/59 (5.1%)	3	1/59 (1.7%)	1	1/58 (1.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	17/59 (28.8%)	27	9/59 (15.3%)	14	10/58 (17.2%)	14
Back pain	6/59 (10.2%)	7	10/59 (16.9%)	17	7/58 (12.1%)	10
Musculoskeletal pain	3/59 (5.1%)	4	2/59 (3.4%)	2	3/58 (5.2%)	4
Musculoskeletal stiffness	1/59 (1.7%)	1	3/59 (5.1%)	3	0/58 (0%)	0
Myalgia	0/59 (0%)	0	1/59 (1.7%)	1	3/58 (5.2%)	4
Neck pain	0/59 (0%)	0	3/59 (5.1%)	5	5/58 (8.6%)	6
Osteopenia	3/59 (5.1%)	3	3/59 (5.1%)	3	0/58 (0%)	0
Pain in extremity	9/59 (15.3%)	13	14/59 (23.7%)	24	9/58 (15.5%)	16
Nervous system disorders
Dizziness	3/59 (5.1%)	3	4/59 (6.8%)	6	7/58 (12.1%)	10
Headache	21/59 (35.6%)	38	24/59 (40.7%)	52	24/58 (41.4%)	69
Hyperreflexia	3/59 (5.1%)	6	1/59 (1.7%)	3	0/58 (0%)	0
Paraesthesia	0/59 (0%)	0	0/59 (0%)	0	3/58 (5.2%)	6
Somnolence	0/59 (0%)	0	0/59 (0%)	0	3/58 (5.2%)	3
Psychiatric disorders
Agitation	0/59 (0%)	0	2/59 (3.4%)	2	3/58 (5.2%)	3
Reproductive system and breast disorders
Dysmenorrhoea	2/59 (3.4%)	2	3/59 (5.1%)	3	1/58 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/59 (0%)	0	3/59 (5.1%)	3	1/58 (1.7%)	1
Cough	21/59 (35.6%)	28	17/59 (28.8%)	29	16/58 (27.6%)	20
Dyspnoea	3/59 (5.1%)	4	6/59 (10.2%)	8	7/58 (12.1%)	12
Epistaxis	3/59 (5.1%)	5	2/59 (3.4%)	2	3/58 (5.2%)	3
Nasal congestion	5/59 (8.5%)	8	5/59 (8.5%)	7	5/58 (8.6%)	7
Oropharyngeal pain	7/59 (11.9%)	8	9/59 (15.3%)	12	12/58 (20.7%)	14
Rhinorrhoea	4/59 (6.8%)	6	4/59 (6.8%)	9	5/58 (8.6%)	5
Throat irritation	0/59 (0%)	0	0/59 (0%)	0	3/58 (5.2%)	4
Tonsillar hypertrophy	3/59 (5.1%)	3	0/59 (0%)	0	0/58 (0%)	0
Skin and subcutaneous tissue disorders
Eczema	3/59 (5.1%)	3	1/59 (1.7%)	1	1/58 (1.7%)	2
Petechiae	0/59 (0%)	0	3/59 (5.1%)	3	0/58 (0%)	0
Pruritus	2/59 (3.4%)	2	3/59 (5.1%)	5	4/58 (6.9%)	4
Rash	5/59 (8.5%)	6	6/59 (10.2%)	7	6/58 (10.3%)	9
Urticaria	0/59 (0%)	0	4/59 (6.8%)	5	3/58 (5.2%)	5
Vascular disorders
Flushing	0/59 (0%)	0	1/59 (1.7%)	1	5/58 (8.6%)	7
Hot flush	1/59 (1.7%)	1	4/59 (6.8%)	6	3/58 (5.2%)	3
Hypertension	4/59 (6.8%)	13	4/59 (6.8%)	18	3/58 (5.2%)	6
Hypotension	1/59 (1.7%)	1	2/59 (3.4%)	3	3/58 (5.2%)	3
Poor venous access	4/59 (6.8%)	8	1/59 (1.7%)	1	3/58 (5.2%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.