Trial Outcomes & Findings for Administration of IV Laronidase Post Bone Marrow Transplant in Hurler (NCT NCT01173016)

NCT ID: NCT01173016

Last Updated: 2020-03-20

Results Overview

To determine the feasibility of giving weekly Laronidase for 2 years in patients with Hurler syndrome after allogeneic transplantation, compliance throughout the study with drug administration, the percentage of adherence to the scheduled weekly infusion for each participant is measured.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 11 participants
• Primary outcome timeframe: 24 months
• Results posted on: 2020-03-20

Participant Flow

Participant milestones

Measure	Laronidase After Transplantation Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Overall Study STARTED	11
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Administration of IV Laronidase Post Bone Marrow Transplant in Hurler

Baseline characteristics by cohort

Measure	Laronidase After Transplantation n=11 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Age, Categorical <=18 years	11 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

To determine the feasibility of giving weekly Laronidase for 2 years in patients with Hurler syndrome after allogeneic transplantation, compliance throughout the study with drug administration, the percentage of adherence to the scheduled weekly infusion for each participant is measured.

Outcome measures

Measure	Laronidase After Transplantation n=10 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Percentage of Adherence to the Scheduled Weekly Infusion by the Participants	99 percentage Interval 79.0 to 100.0

PRIMARY outcome

Timeframe: 24 months

Number of participants experiencing severe adverse events that occur after administration with Laronidase to determine the feasibility of giving weekly Laronidase

Outcome measures

Measure	Laronidase After Transplantation n=11 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Number of Participants Experiencing Severe Adverse Events	1 Participants

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: Baseline growth velocity value was available in six of ten participants. One female participant was excluded from the within-group growth analyses due to a bone age of 14.5 years

difference between baseline and month 24 growth velocities

Outcome measures

Measure	Laronidase After Transplantation n=5 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Changes in Growth Velocity	-1.1 cm/year Standard Deviation 3.8

SECONDARY outcome

Timeframe: Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months

Handgrip strength is measured three times in both hands with a mechanical handheld Biodex System 3 dynamometer (Biodex medical Systems, Inc., Shirley, NY) with the subject in a seated position at each visit; the average for each hand is presented.

Outcome measures

Measure	Laronidase After Transplantation n=10 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Change in Muscle Strength	1.1 kg Standard Deviation 1.9

SECONDARY outcome

Timeframe: Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months

A modified Balke Treadmill Test was performed. Briefly, patients began walking at 2.0 mph with a 2% increase in grade every 2 min. A 12-lead electrocardiogram was monitored continuously throughout the test for the determination of heart rate and dysrhythmias or ischemic changes. Heart rate was measured at the end of each stage (i.e. every 2 min) .

Outcome measures

Measure	Laronidase After Transplantation n=10 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Change in Peak Heart Rate to Monitor "Fitness"	23 bpm Standard Deviation 18

SECONDARY outcome

Timeframe: Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months

Bilateral shoulder flexion, elbow extension, and hip extension were measured using goniometry. Improvements are defined for all joints as >5°.

Outcome measures

Measure	Laronidase After Transplantation n=10 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Number of Participants Showing Improvements in Joint Range of Motion (ROM) Left or right shoulder ROM improvement	4 Participants
Number of Participants Showing Improvements in Joint Range of Motion (ROM) Left or right elbow ROM improvement	3 Participants
Number of Participants Showing Improvements in Joint Range of Motion (ROM) Left or right hip ROM improvement	5 Participants

SECONDARY outcome

Timeframe: Baseline and month 24

Population: two subjects didn't have both baseline and month 24 echo data

Cardiac ultrasounds were obtained at baseline and month 24. Two-dimensional imaging was obtained for determination of anatomy. Shortening fraction (SF [normal > 27%]) was calculated by standard methods to determine the normal systolic cardiac function

Outcome measures

Measure	Laronidase After Transplantation n=8 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Shortening Fraction to Determine Systolic Cardiac Function	38 percentage of systolic cardiac function Interval 34.0 to 52.0

SECONDARY outcome

Timeframe: Baseline and month 24

Population: Two subjects didn't have both baseline and month 24 echo data

Pulse-wave and color Doppler interrogation of cardiac valves was performed for determination of valve regurgitation

Outcome measures

Measure	Laronidase After Transplantation n=8 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Number of Participants With Changes in Cardiac Echo Structural Parameters Mitral regurgitation - unchaged	7 Participants
Number of Participants With Changes in Cardiac Echo Structural Parameters Mitral regurgitation - increased	1 Participants
Number of Participants With Changes in Cardiac Echo Structural Parameters Aortic regurgitation - unchanged	5 Participants
Number of Participants With Changes in Cardiac Echo Structural Parameters Aortic regurgitation - increased	3 Participants

SECONDARY outcome

Timeframe: Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months

6 minute walk test (6MWT) was performed to assess overall physical function and health status. In brief, a 30m hospital corridor marked by colored tape at each end was used. Subjects were instructed to walk from end to end at their self-selected pace, while attempting to cover as much distance as possible in the 6 min. The patients were instructed to walk around the mark as they changed direction. The time and distance covered was recorded, as was the heart rate prior to and immediately after completion of the walk test.

To find the association between the rate of change in 6MWT, and anti drug antibody (ADA) titer, a statistical test is performed adjusting for age at the time of enrollment.

Outcome measures

Measure	Laronidase After Transplantation n=10 Participants Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Correlation of 6 Minute Walk Test With Anti-laronidase Antibody + Status	-14 meters Interval -28.0 to -1.0

Adverse Events

Laronidase After Transplantation

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Laronidase After Transplantation n=11 participants at risk Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Nervous system disorders Syncope	9.1% 1/11 • 24 months
Nervous system disorders Seizure	9.1% 1/11 • 24 months

Other adverse events

Measure	Laronidase After Transplantation n=11 participants at risk Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant \>2 years previously and treated with Laronidase weekly for 2 years after transplant. Laronidase: Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
Immune system disorders Allergy Reaction/Hypersensitivity	9.1% 1/11 • Number of events 4 • 24 months
General disorders Fever	9.1% 1/11 • Number of events 1 • 24 months
Nervous system disorders Headache	9.1% 1/11 • Number of events 1 • 24 months
Immune system disorders Hives	9.1% 1/11 • Number of events 3 • 24 months
Vascular disorders Hypertension	27.3% 3/11 • Number of events 47 • 24 months
General disorders Pain, Right Shoulder	9.1% 1/11 • Number of events 1 • 24 months
Cardiac disorders Sinus Tachycardia	27.3% 3/11 • Number of events 36 • 24 months
Cardiac disorders Hypotension	9.1% 1/11 • Number of events 1 • 24 months

Additional Information

Dr. Paul Orchard

Masonic Cancer Center, University of Minnesota

Phone: 612-626-2313

Email: orcha001@umn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place