Effects of Adalimumab in Mucopolysaccharidosis Types I, II and VI

• ClinicalTrials.gov Identifier: NCT02437253
• Recruitment Status: Completed
• First Posted: May 7, 2015
• Results First Posted: September 15, 2017
• Last Update Posted: September 15, 2017
• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Information provided by (Responsible Party): Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Mucopolysaccharidosis Type I; Mucopolysaccharidosis Type II; Mucopolysaccharidosis Type VI
• Interventions: Drug: Adalimumab; Other: Placebo
• Enrollment: 2

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Adalimumab First, Then Placebo	Placebo First, Then Adalimumab
Arm/Group Description	Participants first received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week.	Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.
Period Title: Overall Study
Started	1	1
Completed	1	1
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Adalimumab First, Then Placebo	Placebo First, Then Adalimumab	Total
Arm/Group Description		Participants first received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks.	Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		1	1	2
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	2 participants
	<=18 years	1 100.0%	1 100.0%	2 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	1 participants	1 participants	2 participants
		15; (15 to 15)	6; (6 to 6)	10.5; (6 to 15)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	2 participants
	Female	1 100.0%	1 100.0%	2 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	2 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	1 100.0%	1 100.0%	2 100.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	1 participants	1 participants	2 participants
		1	1	2

Outcome Measures

1. Primary Outcome

Title	Children's Health Questionnaire - Parent Form 50 Bodily Pain Standardized Score
Description	Children's Health Questionnaire - Parent Form 50 bodily pain (BP) standardized score for participants < 18 years of age. Range is from 0 to 100 (no units) and standardization if determined by comparison to healthy age matched children. Lower values mean increased pain. The difference of change in BP standardized score from day 0 to week 16 during adalimumab treatment minus change in BP standardized score from day 0 to week 16 during placebo treatment is reported.
Time Frame	day 0 to week 16 of treatment with adalimumab versus placebo

Outcome Measure Data

Analysis Population Description

This was a cross-over study so within-individual changes are reported.

Arm/Group Title	Adalimumab First, Then Placebo	Placebo First, Then Adalimumab
Arm/Group Description:	Participants first received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks.	Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.
Overall Number of Participants Analyzed	1	1
Mean (Full Range); Unit of Measure: units on a scale
	1.4; (1.4 to 1.4)	1.0; (1.0 to 1.0)

2. Secondary Outcome

Title	Children's Health Questionnaire - Parent Form 50 Physical Function (PF) Standardized Score
Description	Children's Health Questionnaire - Parent Form 50 physical function (PF) standardized score for participants < 18 years of age. Range is from 0 to 100 (no units) and standardization if determined by comparison to healthy age matched children. Lower values mean decreased physical function. The difference of change in PF standardized score from day 0 to week 16 during adalimumab treatment minus change in PF standardized score from day 0 to week 16 during placebo treatment is reported.
Time Frame	Day 0 to week 16 of treatment with adalimumab versus placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adalimumab First, Then Placebo	Placebo First, Then Adalimumab
Arm/Group Description:	Participants first received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks.	Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.
Overall Number of Participants Analyzed	1	1
Mean (Full Range); Unit of Measure: units on a scale
	0; (0 to 0)	0.4; (0.4 to 0.4)

3. Secondary Outcome

Title	Pain Measured by the Visual Analog Scale (VAS) in the Pediatric Pain Questionnaire (PPQ)
Description	Percent of participants with a >10 mm improvement in either "how you feel now" or "worst pain you had this week" on the VA in the PPQ during adalimumab versus during placebo by either parental or subject report. Range is 0-100 mm; lower number means less pain.
Time Frame	Day 0 to week 16 of treatment with adalimumab versus placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adalimumab First, Then Placebo	Placebo First, Then Adalimumab
Arm/Group Description:	Participants first received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks.	Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.
Overall Number of Participants Analyzed	1	1
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	1 100.0%

4. Secondary Outcome

Title	Range of Motion - Bilateral Shoulder, Elbow, Hip, Knee
Description	Number of joints with a >5 degree more positive change during 16 weeks of adalimumab versus 16 weeks of placebo. A total of eight joints were measured.
Time Frame	Day 0 to week 16 of treatment with adalimumab versus placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adalimumab First, Then Placebo	Placebo First, Then Adalimumab
Arm/Group Description:	Participants first received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week.	Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.
Overall Number of Participants Analyzed	1	1
Measure Type: Number; Unit of Measure: joints
	7	5

5. Secondary Outcome

Title	Anti-ERT Antibodies
Description	Anti-laronidase antibodies for subjects with MPS I. Anti-idursulfase antibodies for subjects with MPS II.
Time Frame	Day 0 to week 16 of treatment with adalimumab versus placebo

Outcome Measure Data

Analysis Population Description

No participants had anti-ERT antibodies

Arm/Group Title	Adalimumab First, Then Placebo	Placebo First, Then Adalimumab
Arm/Group Description:	Participants first received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week.	Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to <30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.
Overall Number of Participants Analyzed	1	1
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Adalimumab		Placebo
Arm/Group Description	20 mg subQ every other week (weight 15 to <30 kg) 40 mg subQ every other week (weight ≥30 kg). Adalimumab: Subjects will be treated with adalimumab (20 mg [weight 15-<30 kg] or 40 mg [weight ≥30 kg] administered subcutaneously [subQ] every other week) or placebo for 16 weeks, then cross-over to the other group for 16 weeks.		Saline placebo injection Placebo: Saline placebo
All-Cause Mortality
	Adalimumab		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/2 (0.00%)		0/2 (0.00%)
Serious Adverse Events
	Adalimumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0.00%)		0/2 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Adalimumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100.00%)		2/2 (100.00%)
Blood and lymphatic system disorders
Thrombocytopenia † [1]	1/2 (50.00%)	1	0/2 (0.00%)	0
Gastrointestinal disorders
Diarrhea † [2]	1/2 (50.00%)	1	0/2 (0.00%)	0
Infections and infestations
Upper Respiratory Infection †	0/2 (0.00%)	0	2/2 (100.00%)	2
Sinusitis †	0/2 (0.00%)	0	1/2 (50.00%)	1
Nervous system disorders
Headache †	0/2 (0.00%)	0	1/2 (50.00%)	1
Psychiatric disorders
Mood lability †	0/2 (0.00%)	0	1/2 (50.00%)	1
Skin and subcutaneous tissue disorders
Injection site erythema †	1/2 (50.00%)	1	0/2 (0.00%)	0
† Indicates events were collected by systematic assessment; [1] Resolved by 2 week recheck without intervention; [2] Resolved after 2 days without intervention

Limitations and Caveats

Small pilot study of 2 participants.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Lynda Polgreen (PI)
• Organization: Los Angeles Biomedical Research Institute at Harbor-UCLA
• Phone: 310-222-1961
• EMail: lpolgreen@labiomed.org

• Responsible Party: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• ClinicalTrials.gov Identifier: NCT02437253
• Other Study ID Numbers: 30535
• First Submitted: May 5, 2015
• First Posted: May 7, 2015
• Results First Submitted: May 3, 2017
• Results First Posted: September 15, 2017
• Last Update Posted: September 15, 2017