Phase 1 N=13 Treatment

Metazym for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

Metachromatic Leukodystrophy (MLD)

Bottom Line

View on ClinicalTrials.gov: NCT00418561 ↗

Enrolled (actual)

Serious AEs

38.5%

Results posted

Aug 2015

Primary outcome: Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) — 4; 5; 4 participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: rhASA - Dose Level 1 (Biological); rhASA - Dose Level 2 (Biological); rhASA - Dose Level 3 (Biological)
Age: Pediatric · 1+ yrs
Sex: All
Sponsor: Shire
Primary completion: Mar 2008

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs)	4; 5; 4	—
PRIMARY Change From Baseline in Gross Motor Function Measure (GMFM) at Week 26	-2.36; -8.29; -10.90	0.0737
PRIMARY Change From Baseline in Cerebrospinal Fluid (CSF) Sulfatide at Week 26	24.55; -3.77; -4.32	0.1115
PRIMARY Number of Participants With Shift From Baseline to Week 26 in Sulfatide Levels in Urine	0; 0; 0; 0; 0; 0	—
PRIMARY Change From Baseline in Mullen's Scales of Early Learning at Week 26	16.28; 0.26; -4.92	0.1268
PRIMARY Maximum Plasma Drug Concentration (Cmax) of Recombinant Human Arylsulphatase A (rhASA)	—	—
PRIMARY Arylsulfatase A (ASA) Activity in Leukocytes	—	—
SECONDARY Change From Baseline in Nerve Conduction Velocity at Week 26	20.38; 25.78; 15.95; -4.00; 2.62; -3.65	—
SECONDARY Number of Participants Who Had Undergone Nerve Biopsy and Had a Normal Nerve at Both Baseline and Week 26	0; 2; 0; 0; 2; 0	—
SECONDARY Number of Participants With Shift From Baseline to Week 26 in Magnetic Resonance Imaging (MRI)-Loes Scores	1; 0; 1; 3; 4; 3	—
SECONDARY Change From Baseline in Paediatric Evaluation of Disability Inventory (PEDI) Scores at Week 26	6.25; 6.00; 4.75; -0.75; -1.50; -1.50	—

Summary

Objectives: The overall objective is to evaluate the safety, efficacy and pharmacokinetics (PK) of rhASA treatment in patients with late infantile MLD. Methodology: This is a single center, open-label study of patients with late infantile MLD. Twelve patients will be enrolled in this study receiving a total of thirteen intravenous infusions of Metazym. One infusion will be given every other week for a period of half a year. After the half year the subjects will continue treatment every other week until safety data is available. Safety (AE/SAE) will be monitored at every visit during this period.

Eligibility Criteria

Inclusion Criteria

Subject's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (Trial-related activities are any procedures that would not have been performed during normal management of the subject).
The patient must have a confirmed diagnosis of MLD as defined by:

ASA activity < 10 nmol/h/mg in leukocytes Presence of elevated sulfatide in urine

The patient must have a confirmed nerve conduction velocity < 2 standard deviations (from the appropriate age level)
The patient must have a residual level of voluntary function (as judged by the investigator), including presence of residual cognitive function (attention, executive and visual functions) as well as the presence of residual voluntary motor function in one upper or lower limb as a minimum.
The patient must have an age at the time of screening ≥ 1 year and < 6 years
The patient must have had onset of symptoms before the age of 4 years
The subject and his/her guardian(s) must have the ability to comply with the clinical protocol
The patients' medical record must document that the legal guardian(s) has had independent counselling or a consultation regarding stem cell transplantation in order to assure that the guardian(s) is fully informed regarding the risks and benefits of this alternative

Exclusion Criteria

Patients will be excluded from this study if they do not meet the specific inclusion criteria, or if any of the following criteria apply:

Lack of voluntary function
Presence of severe pseudo-bulbar signs (weakness and disco-ordination of tongue and swallowing muscles leading to severe difficulty with swallowing)
Spasticity so severe to inhibit transportation
Known multiple sulfatase deficiency
Presence of major congenital abnormality
Presence of known chromosomal abnormality and syndromes affecting psychomotor development
History of stem cell transplantation
Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition
Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
Use of any investigational product within 30 days prior to study enrolment or currently enrolled in another study which involves clinical investigations
Received ERT with rhASA from any source
Planned or anticipated initiation of antispastic treatment after trial initiation

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00418561). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.