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

• Sponsor: BioMarin Pharmaceutical (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01242111
• Collaborator: (none)
• Enrollment: 20
• Locations: 4
• Arm: 1
• Duration (Months): 44
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This multicenter, open-label extension study is designed to assess long-term efficacy and safety of 2.0 milligrams (mg)/kilogram(kg)/week of BMN 110 in patients diagnosed with Mucopolysaccharidosis IVA (MPS IVA). Patients with MPS IVA, who enrolled in a prior BioMarin sponsored clinical study of BMN 110 (NCT00884949; Study Identification Number MOR-002), were eligible to enroll in this study (except patients who enrolled in NCT01275066; Study Identification Number MOR-004).

Condition or Disease	Intervention/Treatment	Phase
MPS IV A; Mucopolysaccharidosis IVA; Morquio A Syndrome	Drug: BMN 110	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Multinational, Open-Label, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BMN 110	Drug: BMN 110; Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.

Outcome Measures

Primary Outcome Measures

1. Safety Evaluation [Entire Study Period, up to 240 weeks]

   The primary objective of the study is to evaluate the safety of weekly infusions of BMN 110; the safety variables included Adverse Events (AEs). The primary outcome measure data is presented in more detail under the Adverse Events section.

Secondary Outcome Measures

1. Change From Baseline in Endurance as Measured by the 6-minute Walk Test During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial]

   Change from baseline in meters in 6-minute Walk Test. As a measure of endurance, a 6-minute walk test (6MWT) was performed according to the American Thoracic Society Guidelines. Patients were instructed to walk as far as possible in 6 minutes.

2. Change in Baseline in Endurance as Measured by the 3 Minute Stair Climb During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial]

   Change from baseline in the 3-minute Stair Climb Test (3MSCT). Patients walked up stairs that have a railing, which could be used for support, for 3 minutes, with the number of stairs climbed recorded. The test result was the number of steps climbed per minute.

3. Percent Change From Baseline in Urine Keratan Sulfate (uKS) Levels During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 168 weeks during the MOR-100 extension trial]

   Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100%

4. Percent Change From Baseline in Respiratory Function Test MVV During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial]

   Percent Change from baseline in Maximum Voluntary Ventilation.

5. Percent Change From Baseline in Respiratory Function Test FVC During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial]

   Percent Change from baseline in Forced Vital Capacity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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.

• 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 Baseline and be willing to have additional pregnancy tests during the study.

• Must have enrolled in a prior BioMarin sponsored clinical study of BMN 110.

Exclusion Criteria:

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

• Use of any investigational product (other than BMN 110 in a prior clinical study) or investigational medical device within 30 days prior to Baseline, 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.

• Were enrolled in MOR-004 (patients from MOR-004 may be eligible to participate in a separate, appropriately designed, extension study).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham		United Kingdom
2		Dumfries		United Kingdom
3		London		United Kingdom
4		Manchester		United Kingdom

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
• The BioMarin Morquio Program

Publications

None provided.

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT01242111
• Other Study ID Numbers: MOR-100
• First Posted: Nov 16, 2010
• Last Update Posted: Sep 30, 2015
• Last Verified: Aug 1, 2015

• 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; Mucopolysaccharidosis IV; Syndrome

Study Results

Participant Flow

Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
Period Title: Overall Study
STARTED	20
COMPLETED	17
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.4 (2.90)
Age, Customized (participants) [Number]
>=4 to < 8 years	10 50%
>=8 to <10 years	5 25%
>=10 to <=18 years	5 25%
Sex: Female, Male (Count of Participants)
Female	8 40%
Male	12 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	20 100%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%
Asian	9 45%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	9 45%
Other	2 10%
Region of Enrollment (participants) [Number]
United Kingdom	20 100%

Outcome Measures

1. Primary Outcome

Title	Safety Evaluation
Description	The primary objective of the study is to evaluate the safety of weekly infusions of BMN 110; the safety variables included Adverse Events (AEs). The primary outcome measure data is presented in more detail under the Adverse Events section.
Time Frame	Entire Study Period, up to 240 weeks

Outcome Measure Data

Analysis Population Description

The primary outcome measure data is presented in more detail under the Adverse Events section.

Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
Measure Participants	20
Serious Adverse Events	19 95%
Other (Not Including Serious) Adverse Events	20 100%

2. Secondary Outcome

Title	Change From Baseline in Endurance as Measured by the 6-minute Walk Test During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100).
Description	Change from baseline in meters in 6-minute Walk Test. As a measure of endurance, a 6-minute walk test (6MWT) was performed according to the American Thoracic Society Guidelines. Patients were instructed to walk as far as possible in 6 minutes.
Time Frame	Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population (all subjects who enrolled in the study). Two patients were either physically (score was designated as 0 m) or developmentally (score was set to missing) unable to perform the 6MWT. The analysis was based on observed cases.

Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
Measure Participants	20
MOR-002 Week 12 Change from Baseline (n=19)	-20.7 (85.95)
MOR-002 Week 24 Change from Baseline (n=17)	16.3 (71.74)
MOR-002 Week 36 Change from Baseline (n=17)	13.8 (63.25)
MOR-002 Week 48 Change from Baseline (n=17)	-4.8 (64.70)
MOR-002 Week 72 Change from Baseline (n=17)	4.0 (87.24)
MOR-100 Week 0 Change from Baseline (n=16)	15.7 (89.00)
MOR-100 Week 24 Change from Baseline (n=16)	24.5 (101.23)
MOR-100 Week 48 Change from Baseline (n=16)	6.8 (98.66)
MOR-100 Week 72 Change from Baseline (n=17)	-49.8 (132.63)
MOR-100 Week 96 Change from Baseline (n=16)	11.2 (85.24)
MOR-100 Week 120 Change from Baseline (n=16)	4.2 (94.09)
MOR-100 Week 144 Change from Baseline (n=13)	3.1 (106.82)
MOR-100 Week 192 Change from Baseline (n=9)	-37.1 (103.96)

3. Secondary Outcome

Title	Change in Baseline in Endurance as Measured by the 3 Minute Stair Climb During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100).
Description	Change from baseline in the 3-minute Stair Climb Test (3MSCT). Patients walked up stairs that have a railing, which could be used for support, for 3 minutes, with the number of stairs climbed recorded. The test result was the number of steps climbed per minute.
Time Frame	Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population (all subjects who enrolled in the study). One patient was developmentally unable to perform the 3MSCT and the test scores were set to missing. The analysis was based on observed cases.

Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
Measure Participants	20
MOR-002 Week 12 Change from Baseline (n=19)	0.3 (14.07)
MOR-002 Week 24 Change from Baseline (n=17)	6.1 (8.66)
MOR-002 Week 36 Change from Baseline (n=17)	7.8 (13.69)
MOR-002 Week 48 Change from Baseline (n=17)	9.7 (14.42)
MOR-002 Week 72 Change from Baseline (n=17)	9.7 (13.91)
MOR-100 Week 0 Change from Baseline (n=16)	12.7 (13.96)
MOR-100 Week 24 Change from Baseline (n=16)	13.4 (17.07)
MOR-100 Week 48 Change from Baseline (n=16)	6.6 (16.87)
MOR-100 Week 72 Change from Baseline (n=16)	-1.4 (21.11)
MOR-100 Week 96 Change from Baseline (n=16)	9.9 (18.84)
MOR-100 Week 120 Change from Baseline (n=16)	6.2 (14.41)
MOR-100 Week 144 Change from Baseline (n=12)	5.4 (11.93)
MOR-100 Week 192 Change from Baseline (n=7)	-0.2 (10.34)

4. Secondary Outcome

Title	Percent Change From Baseline in Urine Keratan Sulfate (uKS) Levels During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100).
Description	Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100%
Time Frame	Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 168 weeks during the MOR-100 extension trial

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population (all subjects who enrolled in the study). The analysis was based on observed cases.

Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
Measure Participants	20
MOR-002 Wk 12 Percent Change from Baseline (n=19)	-23.2 (19.04)
MOR-002 Wk 24 Percent Change from Baseline (n=18)	-27.9 (17.92)
MOR-002 Wk 36 Percent Change from Baseline (n=18)	-40.6 (20.16)
MOR-002 Wk 72 Percent Change from Baseline (n=17)	-32.2 (17.10)
MOR-100 Wk 0 Percent Change from Baseline (n=17)	-30.0 (19.23)
MOR-100 Wk 24 Percent Change from Baseline (n=17)	-43.6 (19.56)
MOR-100 Wk 48 Percent Change from Baseline (n=16)	-41.9 (19.29)
MOR-100 Wk 72 Percent Change from Baseline (n=12)	-36.4 (36.70)
MOR-100 Wk 96 Percent Change from Baseline (n=17)	-49.7 (19.93)
MOR-100 Wk 120 Percent Change from Baseline (n=16)	-49.3 (22.28)
MOR-100 Wk 144 Percent Change from Baseline (n=16)	-56.6 (19.54)
MOR-100 Wk 168 Percent Change from Baseline (n=15)	-58.9 (16.02)

5. Secondary Outcome

Title	Percent Change From Baseline in Respiratory Function Test MVV During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100).
Description	Percent Change from baseline in Maximum Voluntary Ventilation.
Time Frame	Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population (all subjects who enrolled in the study). The analysis was based on observed cases.

Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
Measure Participants	20
MOR-002 Wk 12 Percent Change from Baseline (n=14)	9.9 (21.29)
MOR-002 Wk 24 Percent Change from Baseline (n=13)	11.0 (21.48)
MOR-002 Wk 36 Percent Change from Baseline (n=14)	10.5 (17.43)
MOR-002 Wk 72 Percent Change from Baseline (n=14)	18.4 (20.77)
MOR-100 Wk 0 Percent Change from Baseline (n=13)	11.1 (16.44)
MOR-100 Wk 24 Percent Change from Baseline (n=13)	9.8 (22.25)
MOR-100 Wk 48 Percent Change from Baseline (n=12)	3.5 (17.78)
MOR-100 Wk 72 Percent Change from Baseline (n=13)	10.1 (27.83)
MOR-100 Wk 96 Percent Change from Baseline (n=12)	-4.9 (35.53)
MOR-100 Wk 120 Percent Change from Baseline (n=13)	-3.3 (28.35)
MOR-100 Wk 144 Percent Change from Baseline (n=11)	-3.5 (34.61)
MOR-100 Wk 192 Percent Change from Baseline (n=6)	28.2 (38.78)

6. Secondary Outcome

Title	Percent Change From Baseline in Respiratory Function Test FVC During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100).
Description	Percent Change from baseline in Forced Vital Capacity.
Time Frame	Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population (all subjects who enrolled in the study). The analysis was based on observed cases.

Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
Measure Participants	20
MOR-002 Wk 12 Percent Change from Baseline (n=18)	3.4 (10.85)
MOR-002 Wk 24 Percent Change from Baseline (n=16)	0.2 (16.60)
MOR-002 Wk 36 Percent Change from Baseline (n=16)	10.7 (20.81)
MOR-002 Wk 72 Percent Change from Baseline (n=16)	12.5 (14.88)
MOR-100 Wk 0 Percent Change from Baseline (n=15)	11.8 (14.97)
MOR-100 Wk 24 Percent Change from Baseline (n=14)	15.3 (16.31)
MOR-100 Wk 48 Percent Change from Baseline (n=13)	15.8 (16.56)
MOR-100 Wk 72 Percent Change from Baseline (n=15)	16.1 (21.96)
MOR-100 Wk 96 Percent Change from Baseline (n=14)	14.8 (17.36)
MOR-100 Wk 120 Percent Change from Baseline (n=16)	22.8 (21.14)
MOR-100 Wk 144 Percent Change from Baseline (n=12)	17.5 (24.32)
MOR-100 Wk 192 Percent Change from Baseline (n=7)	18.6 (30.98)

Adverse Events

Time Frame	Study Period, up to 240 weeks
Arm/Group Title	BMN 110
Arm/Group Description	BMN 110: Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.
All Cause Mortality
	BMN 110
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	BMN 110
	Affected / at Risk (%)	# Events
Total	19/20 (95%)
Cardiac disorders
Supraventricular tachycardia	1/20 (5%)	1
Tachycardia	1/20 (5%)	1
General disorders
Gait disturbance	1/20 (5%)	1
Infusion site inflammation	1/20 (5%)	1
Infusion site reaction	2/20 (10%)	3
Malaise	1/20 (5%)	1
Pyrexia	2/20 (10%)	2
Immune system disorders
Type I hypersensitivity	1/20 (5%)	1
Infections and infestations
Abdominal abscess	1/20 (5%)	1
Abscess limb	1/20 (5%)	1
Catheter site infection	1/20 (5%)	1
Device related infection	2/20 (10%)	2
Infusion site infection	1/20 (5%)	1
Lobar pneumonia	1/20 (5%)	1
Lower respiratory tract infection	2/20 (10%)	5
Otitis media	3/20 (15%)	3
Pneumonia	1/20 (5%)	1
Pneumonia mycoplasmal	1/20 (5%)	1
Respiratory syncytial virus infection	1/20 (5%)	1
Viral infection	2/20 (10%)	2
Injury, poisoning and procedural complications
Infusion related reaction	1/20 (5%)	3
Procedural pain	1/20 (5%)	1
Road traffic accident	1/20 (5%)	1
Skull fracture	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Knee deformity	6/20 (30%)	7
Pain in extremity	1/20 (5%)	1
Nervous system disorders
Cervical cord compression	2/20 (10%)	2
Psychiatric disorders
Panic attack	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	1/20 (5%)	1
Sleep apnoea syndrome	1/20 (5%)	2
Skin and subcutaneous tissue disorders
Rash	1/20 (5%)	3
Rash maculo-papular	1/20 (5%)	1
Surgical and medical procedures
Abscess drainage	1/20 (5%)	2
Bone operation	1/20 (5%)	1
Central venous catheterisation	2/20 (10%)	2
Knee operation	2/20 (10%)	2
Medical device implantation	2/20 (10%)	2
Medical device removal	2/20 (10%)	2
Orthopaedic procedure	3/20 (15%)	3
Vascular disorders
Flushing	1/20 (5%)	2
Hypertension	1/20 (5%)	1
Jugular vein distension	1/20 (5%)	1
Poor venous access	8/20 (40%)	9
Other (Not Including Serious) Adverse Events
	BMN 110
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Blood and lymphatic system disorders
Eosinophilia	1/20 (5%)	1
Lymphadenopathy	4/20 (20%)	5
Cardiac disorders
Aortic valve incompetence	3/20 (15%)	3
Diastolic dysfunction	1/20 (5%)	1
Mitral valve disease	2/20 (10%)	2
Mitral valve incompetence	3/20 (15%)	3
Pulmonary valve incompetence	3/20 (15%)	3
Tachycardia	3/20 (15%)	6
Tricuspid valve incompetence	3/20 (15%)	3
Congenital, familial and genetic disorders
Congenital heart valve disorder	1/20 (5%)	1
Ear and labyrinth disorders
Cerumen impaction	3/20 (15%)	3
Deafness	1/20 (5%)	1
Deafness neurosensory	1/20 (5%)	2
Ear canal erythema	1/20 (5%)	1
Ear discomfort	1/20 (5%)	1
Ear disorder	1/20 (5%)	1
Ear pain	12/20 (60%)	41
Ear pruritus	1/20 (5%)	1
Hyperacusis	1/20 (5%)	2
Hypoacusis	2/20 (10%)	4
Middle ear disorder	1/20 (5%)	1
Motion sickness	4/20 (20%)	9
Otorrhoea	2/20 (10%)	2
Tinnitus	1/20 (5%)	1
Tympanic membrane disorder	3/20 (15%)	3
Tympanic membrane hyperaemia	2/20 (10%)	2
Tympanic membrane perforation	1/20 (5%)	1
Endocrine disorders
Autoimmune thyroiditis	1/20 (5%)	2
Eye disorders
Conjunctivitis	3/20 (15%)	4
Dry eye	1/20 (5%)	1
Eye discharge	1/20 (5%)	1
Eye pain	1/20 (5%)	1
Eye pruritus	1/20 (5%)	1
Eye swelling	2/20 (10%)	3
Eyelid cyst	1/20 (5%)	1
Ocular hyperaemia	1/20 (5%)	1
Gastrointestinal disorders
Abdominal discomfort	2/20 (10%)	2
Abdominal pain	12/20 (60%)	27
Abdominal pain upper	11/20 (55%)	33
Constipation	5/20 (25%)	5
Dental caries	3/20 (15%)	5
Dental plaque	1/20 (5%)	1
Diarrhoea	12/20 (60%)	28
Dyspepsia	1/20 (5%)	1
Faecal incontinence	1/20 (5%)	2
Gastrooesophageal reflux disease	2/20 (10%)	3
Gingival hyperpigmentation	1/20 (5%)	1
Glossodynia	1/20 (5%)	1
Haematemesis	1/20 (5%)	1
Lip disorder	1/20 (5%)	1
Lip pain	2/20 (10%)	2
Mouth ulceration	1/20 (5%)	1
Nausea	5/20 (25%)	8
Retching	2/20 (10%)	3
Tongue discolouration	1/20 (5%)	1
Tooth deposit	1/20 (5%)	1
Tooth disorder	1/20 (5%)	1
Toothache	5/20 (25%)	8
Vomiting	16/20 (80%)	92
General disorders
Application site reaction	1/20 (5%)	1
Application site vesicles	1/20 (5%)	1
Catheter site erythema	3/20 (15%)	9
Catheter site extravasation	7/20 (35%)	12
Catheter site inflammation	1/20 (5%)	1
Catheter site oedema	1/20 (5%)	1
Catheter site pain	4/20 (20%)	5
Catheter site rash	1/20 (5%)	1
Catheter site related reaction	2/20 (10%)	3
Catheter site scab	1/20 (5%)	1
Catheter site swelling	2/20 (10%)	6
Chest pain	1/20 (5%)	2
Chills	1/20 (5%)	1
Device connection issue	1/20 (5%)	1
Device dislocation	1/20 (5%)	2
Device expulsion	1/20 (5%)	2
Device leakage	1/20 (5%)	1
Device malfunction	1/20 (5%)	1
Device occlusion	3/20 (15%)	3
Extravasation	2/20 (10%)	3
Fatigue	7/20 (35%)	11
Feeling hot	2/20 (10%)	2
Gait disturbance	3/20 (15%)	4
Influenza like illness	3/20 (15%)	3
Infusion site erythema	1/20 (5%)	1
Infusion site extravasation	1/20 (5%)	2
Infusion site pain	1/20 (5%)	1
Infusion site reaction	1/20 (5%)	3
Injection site reaction	1/20 (5%)	1
Local swelling	2/20 (10%)	3
Malaise	4/20 (20%)	8
Medical device complication	2/20 (10%)	4
Medical device site reaction	1/20 (5%)	1
Pain	6/20 (30%)	12
Pyrexia	18/20 (90%)	103
Vaccination site pain	2/20 (10%)	2
Hepatobiliary disorders
Hepatomegaly	1/20 (5%)	2
Immune system disorders
Drug hypersensitivity	1/20 (5%)	1
Seasonal allergy	5/20 (25%)	8
Infections and infestations
Abdominal abscess	1/20 (5%)	1
Catheter site infection	1/20 (5%)	1
Ear infection	6/20 (30%)	15
Eye infection	2/20 (10%)	2
Fungal infection	1/20 (5%)	1
Fungal skin infection	2/20 (10%)	2
Furuncle	3/20 (15%)	4
Gastroenteritis viral	1/20 (5%)	1
Gingivitis	2/20 (10%)	2
Helminthic infection	1/20 (5%)	1
Herpes simplex	1/20 (5%)	2
Herpes zoster	2/20 (10%)	2
Impetigo	1/20 (5%)	3
Infection	2/20 (10%)	2
Influenza	1/20 (5%)	1
Lice infestation	1/20 (5%)	2
Localised infection	2/20 (10%)	2
Lower respiratory tract infection	5/20 (25%)	13
Molluscum contagiosum	1/20 (5%)	2
Nail infection	1/20 (5%)	1
Nasopharyngitis	17/20 (85%)	53
Oral candidiasis	1/20 (5%)	1
Otitis externa	1/20 (5%)	1
Otitis media	3/20 (15%)	3
Paronychia	1/20 (5%)	1
Pharyngitis	1/20 (5%)	1
Postoperative wound infection	1/20 (5%)	1
Rash pustular	1/20 (5%)	1
Rhinitis	5/20 (25%)	8
Skin infection	3/20 (15%)	3
Subcutaneous abscess	1/20 (5%)	1
Tinea pedis	4/20 (20%)	4
Tonsillitis	3/20 (15%)	5
Upper respiratory tract infection	5/20 (25%)	5
Urinary tract infection	1/20 (5%)	2
Varicella	1/20 (5%)	1
Viral infection	1/20 (5%)	1
Viral upper respiratory tract infection	1/20 (5%)	1
Wound infection	1/20 (5%)	1
Injury, poisoning and procedural complications
Arthropod bite	4/20 (20%)	5
Arthropod sting	1/20 (5%)	1
Contusion	6/20 (30%)	8
Ear injury	1/20 (5%)	1
Excoriation	4/20 (20%)	4
Eye contusion	3/20 (15%)	3
Face injury	1/20 (5%)	1
Fall	8/20 (40%)	20
Head injury	8/20 (40%)	14
Infusion related reaction	2/20 (10%)	2
Injury	2/20 (10%)	2
Laceration	2/20 (10%)	2
Ligament sprain	1/20 (5%)	1
Limb injury	3/20 (15%)	4
Lip injury	1/20 (5%)	1
Neck injury	1/20 (5%)	1
Occupational exposure to radiation	1/20 (5%)	1
Periorbital contusion	1/20 (5%)	1
Post procedural complication	1/20 (5%)	1
Procedural headache	1/20 (5%)	1
Procedural pain	7/20 (35%)	7
Procedural vomiting	1/20 (5%)	1
Scar	3/20 (15%)	3
Scratch	1/20 (5%)	1
Skeletal injury	1/20 (5%)	1
Sunburn	1/20 (5%)	1
Thermal burn	1/20 (5%)	1
Upper limb fracture	1/20 (5%)	1
Wound complication	1/20 (5%)	1
Investigations
Alanine aminotransferase increased	1/20 (5%)	1
Aspartate aminotransferase increased	1/20 (5%)	1
Aspiration joint	1/20 (5%)	1
Blood cholesterol increased	2/20 (10%)	2
Blood immunoglobulin E increased	6/20 (30%)	6
Blood immunoglobulin G decreased	1/20 (5%)	1
Blood lactate dehydrogenase increased	1/20 (5%)	1
Blood pressure systolic increased	1/20 (5%)	1
Blood sodium increased	1/20 (5%)	1
Body temperature increased	4/20 (20%)	6
Breath sounds abnormal	1/20 (5%)	1
Cardiac murmur	2/20 (10%)	3
Computerised tomogram	1/20 (5%)	1
Electrocardiogram T wave amplitude decreased	1/20 (5%)	2
Eosinophil count increased	2/20 (10%)	3
Eosinophil percentage increased	1/20 (5%)	1
Liver palpable subcostal	1/20 (5%)	1
Nuclear magnetic resonance imaging	6/20 (30%)	8
Nuclear magnetic resonance imaging spinal	1/20 (5%)	1
Oxygen saturation decreased	1/20 (5%)	3
Protein total abnormal	1/20 (5%)	1
Protein urine	1/20 (5%)	2
Respiratory rate increased	3/20 (15%)	3
Ultrasound scan abnormal	1/20 (5%)	1
Weight increased	2/20 (10%)	4
Metabolism and nutrition disorders
Appetite disorder	2/20 (10%)	2
Decreased appetite	2/20 (10%)	3
Dehydration	1/20 (5%)	1
Hypercholesterolaemia	1/20 (5%)	2
Vitamin D deficiency	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	12/20 (60%)	58
Atlantoaxial instability	1/20 (5%)	1
Axillary mass	1/20 (5%)	1
Back pain	9/20 (45%)	17
Bursitis	1/20 (5%)	1
Joint instability	1/20 (5%)	1
Joint stiffness	1/20 (5%)	2
Joint swelling	2/20 (10%)	2
Knee deformity	2/20 (10%)	2
Mobility decreased	5/20 (25%)	6
Muscle spasms	1/20 (5%)	3
Muscular weakness	2/20 (10%)	3
Musculoskeletal chest pain	1/20 (5%)	1
Musculoskeletal pain	2/20 (10%)	3
Myalgia	1/20 (5%)	1
Neck pain	8/20 (40%)	12
Pain in extremity	17/20 (85%)	76
Pain in jaw	1/20 (5%)	1
Nervous system disorders
Ageusia	1/20 (5%)	1
Areflexia	1/20 (5%)	1
Cervical cord compression	1/20 (5%)	1
Clonus	3/20 (15%)	4
Dizziness	4/20 (20%)	7
Headache	16/20 (80%)	100
Lethargy	5/20 (25%)	5
Migraine	1/20 (5%)	1
Neuralgia	1/20 (5%)	1
Paraesthesia	1/20 (5%)	1
Reflexes abnormal	1/20 (5%)	1
Spinal cord compression	1/20 (5%)	2
Psychiatric disorders
Anxiety	1/20 (5%)	1
Insomnia	2/20 (10%)	3
Renal and urinary disorders
Dysuria	1/20 (5%)	1
Enuresis	1/20 (5%)	3
Incontinence	1/20 (5%)	3
Polyuria	1/20 (5%)	1
Urinary incontinence	1/20 (5%)	1
Reproductive system and breast disorders
Balanitis	2/20 (10%)	2
Dysmenorrhoea	2/20 (10%)	3
Genital ulceration	1/20 (5%)	1
Menorrhagia	1/20 (5%)	1
Penile pain	1/20 (5%)	1
Perineal ulceration	1/20 (5%)	1
Scrotal erythema	1/20 (5%)	1
Vulvovaginal pruritus	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	2/20 (10%)	3
Cough	18/20 (90%)	81
Dry throat	1/20 (5%)	1
Dysphonia	1/20 (5%)	2
Dyspnoea	4/20 (20%)	5
Dyspnoea exertional	1/20 (5%)	1
Epistaxis	4/20 (20%)	12
Nasal congestion	2/20 (10%)	3
Nasal obstruction	5/20 (25%)	6
Oropharyngeal pain	15/20 (75%)	31
Pharyngeal disorder	1/20 (5%)	1
Pharyngeal erythema	1/20 (5%)	1
Pharyngeal oedema	1/20 (5%)	1
Productive cough	2/20 (10%)	3
Rales	1/20 (5%)	1
Respiratory failure	1/20 (5%)	1
Rhinitis allergic	1/20 (5%)	1
Rhinorrhoea	3/20 (15%)	6
Sleep apnoea syndrome	1/20 (5%)	1
Tachypnoea	1/20 (5%)	2
Wheezing	4/20 (20%)	6
Skin and subcutaneous tissue disorders
Acne	2/20 (10%)	2
Dermatitis	1/20 (5%)	1
Dermatitis contact	1/20 (5%)	1
Dermatitis diaper	1/20 (5%)	1
Dry skin	5/20 (25%)	6
Eczema	2/20 (10%)	3
Eczema asteatotic	1/20 (5%)	1
Erythema	4/20 (20%)	43
Lichen planus	1/20 (5%)	1
Miliaria	1/20 (5%)	1
Onychomadesis	1/20 (5%)	1
Pain of skin	1/20 (5%)	1
Papule	2/20 (10%)	2
Petechiae	1/20 (5%)	1
Pigmentation disorder	6/20 (30%)	14
Pruritus	5/20 (25%)	11
Psoriasis	1/20 (5%)	3
Rash	11/20 (55%)	34
Rash erythematous	1/20 (5%)	1
Rash generalised	1/20 (5%)	1
Rash maculo-papular	5/20 (25%)	35
Skin depigmentation	1/20 (5%)	1
Skin discolouration	1/20 (5%)	1
Skin disorder	4/20 (20%)	5
Skin exfoliation	1/20 (5%)	1
Skin mass	2/20 (10%)	4
Urticaria	2/20 (10%)	53
Surgical and medical procedures
Catheter removal	1/20 (5%)	2
Cautery to nose	1/20 (5%)	1
Central venous catheterisation	1/20 (5%)	1
Ear tube insertion	1/20 (5%)	1
Medical device removal	4/20 (20%)	4
Thrombectomy	1/20 (5%)	1
Vascular disorders
Flushing	4/20 (20%)	8
Hot flush	2/20 (10%)	2
Hypertension	3/20 (15%)	6
Hypotension	2/20 (10%)	3
Poor venous access	3/20 (15%)	6
Thrombosis	2/20 (10%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

PI cannot publish any data prior to multi-centre publication. If publication related to sub-sets of data it shall make reference to the relevant multi-centre publication. PI agrees to submit material to Sponsor for review at least 60 days prior to publication and incorporate all reasonable comments. During review, Sponsor may request that publication be delayed for up to 6 months from date of first submission to Sponsor in order for Sponsor to take steps to protect its proprietary information.