Cognitive Decline, Mucopolysaccharidosis I
Conditions
Brief summary
This is a five-year extension study of the pilot study, Intrathecal Enzyme Replacement for Cognitive Decline in MPS I. Participants must have completed the pilot study to participate in this study.
Interventions
DRUGIntrathecal recombinant human alpha iduronidase
Intrathecal recombinant human alpha iduronidase every 3 months
Sponsors
University of Minnesota
UCSF Benioff Children's Hospital Oakland
University of California, Los Angeles
The Ryan Foundation
Rare Diseases Clinical Research Network
National Institute of Neurological Disorders and Stroke (NINDS)
agnes chen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subject has completed the MIRC-002 study of intrathecal enzyme replacement therapy for cognitive decline in mucopolysaccharidosis I 2. Age six years or older. 3. Subject and/or guardian willing and able to provide written informed consent. 4. Negative urine pregnancy test at screening (non-sterile females of child-bearing potential only) 5. Currently using two acceptable methods of birth control as determined by the investigator and willing to continue to use acceptable birth control during their participation in the study (non-sterile females of child-bearing potential who are sexually active only) 6. Willing and able to comply with study procedures. For example, the subjects must be able to complete written and computer-based testing. The subjects must be able to lie still in the MRI scanner for at least 40 minutes without sedation.
Exclusion criteria
1. The subject has undergone hematopoietic stem cell transplantation 2. Recent initiation of intravenous Aldurazyme® therapy with less than 6 months of therapy. Subjects who have been receiving Aldurazyme® therapy for more than 6 months, and those who have never received Aldurazyme® therapy, will be allowed to enroll 3. Pregnant or lactating, or considering pregnancy 4. Receipt of an investigational drug or procedure other than intrathecal Aldurazyme® within 30 days of enrollment 5. A condition, medical or other, that prevents participation in the study, including severe auditory or visual impairment, significant lumbar pathology, lumbar catheter, or recent major surgery within 6 weeks that would preclude their ability to participate. 6. Infusion reactions to intravenous or intrathecal Aldurazyme® therapy that are life-threatening or require emergent intervention such as epinephrine, cardiopulmonary resuscitation, or hospitalization 7. The subject has severely impaired spinal CSF flow, demonstrated by failure of appearance of radionuclide in the basal cisterns by 4 hours after intra-lumbar administration. 8. The subject has a coagulopathy, as identified by a platelet count of less than 50,000, an INR of 1.5 or greater, or a PTT that is 1.5 times the upper limit of normal for the laboratory from which it was drawn.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hopkins Verbal Learning Test | zero to 48 months | Mean intra-subject change in total recall score on the Hopkins Verbal Learning Test between baseline/screening for MIRC-002 and the subject's final visit. The Hopkins Verbal Learning Test measures verbal memory. The subject is read a list of words and asked to memorize as many words as possible. The scale ranges from 0 to 36, with higher scores indicating a better outcome. Two relevant time points: Baseline and the subject's final visit. Because this study ended prematurely for due to the pandemic, the subject's final visit was at the 12-month time point for one subject, 24-months for one subject, 36-months for two subjects, and 48-months for two subjects. Calculation: The total recall score at Baseline was subtracted from the total recall score at the subject's final visit and mean change and standard deviation were reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label Treatment laronidase 1.74 mg IT q 3 months for five years
Intrathecal recombinant human alpha iduronidase: Intrathecal recombinant human alpha iduronidase every 3 months | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Open-label Treatment |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 19.33 years STANDARD_DEVIATION 3.25 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment Canada | 1 Participants |
| Region of Enrollment United States | 5 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 3 / 6 |
Outcome results
Primary
Hopkins Verbal Learning Test
Mean intra-subject change in total recall score on the Hopkins Verbal Learning Test between baseline/screening for MIRC-002 and the subject's final visit. The Hopkins Verbal Learning Test measures verbal memory. The subject is read a list of words and asked to memorize as many words as possible. The scale ranges from 0 to 36, with higher scores indicating a better outcome. Two relevant time points: Baseline and the subject's final visit. Because this study ended prematurely for due to the pandemic, the subject's final visit was at the 12-month time point for one subject, 24-months for one subject, 36-months for two subjects, and 48-months for two subjects. Calculation: The total recall score at Baseline was subtracted from the total recall score at the subject's final visit and mean change and standard deviation were reported.
Time frame: zero to 48 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Treatment | Hopkins Verbal Learning Test | -1.67 score on a scale | Standard Deviation 2.58 |