Clinical trial NCT00957749: Study of cPMP (Precusor Z) to Treat Molybdenum Cofactor Deficiency (MoCD) Type A
Official title: A Multicenter, Open-Label Study of the Safety, Tolerability, and Pharmacodynamics of Intravenously Administered cPMP (Precursor Z) in Patients With Molybdenum Cofactor Deficiency Type A
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Molybdenum Cofactor Deficiency Type A
Lead sponsor: Orphatech Pharmaceuticals, GmbH
Sponsor class: INDUSTRY
First posted: 2009-08-12
Enrollment: 10
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Molybdenum Cofactor Deficiency Type A (MoCD) is a very rare autosomal recessive disorder that is essentially fatal early in life. Naturally occurring cPMP is present in the body of all healthy normal individuals. It is processed to molybdopterin, which is further processed to molybdenum cofactor. Molybdenum cofactor is essential for the function of important enzymes.

There is currently no treatment for MoCD, and affected infants develop severe neurological damage which often results in infant death.

This study is the first clinical trial to investigate the potential of replacement of cPMP to infants with MoCD Type A. The safety, tolerability, and pharmacodynamics of daily intravenous administration of cPMP over 3 months will be determined.


Eligibility criteria: Inclusion Criteria:

* Neonate or infant, less then 6 weeks at the time of diagnosis, age less than 8 weeks at start of treatment with the study medication. It is important to diagnose the condition and initiate treatment as soon after birth as possible.
* Documented diagnosis of molybdenum cofactor deficiency (MoCD) Type A based on the absence of cPMP and the presence of sulfite and s-sulfocysteine in the urine, absence of urothione in the urine and genetic analysis showing a mutation in the MOCS1 gene
* A parent or legal guardian voluntarily provided written informed consent to participate in the study and comply with study procedures.
* Approval of the study protocol by the local HE / IRB and government or regulatory authorities (if applicable)

Exclusion Criteria:

* MoCD Type B (MOCS2 mutation) or Type C (gephyrin gene mutation)
* Sulfite oxidase deficiency
* Patients older than 6 weeks at the time of diagnosis

Primary outcomes:
measure: Urine biomarkers SSC and sulfite
timeFrame: Daily collection throughout study; analyzed at 3 months
Secondary outcomes:
measure: neurological examination
timeFrame: collected daily; analyzed at 3 months
measure: Safety measures (vital signs, adverse events)
timeFrame: collected daily; analyzed at 3 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Monash Medical Centre
state: Victoria
Study officials:
affiliation: Monash Medical Centre
name: Alex Veldman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schwarz G, Santamaria-Araujo JA, Wolf S, Lee HJ, Adham IM, Grone HJ, Schwegler H, Sass JO, Otte T, Hanzelmann P, Mendel RR, Engel W, Reiss J. Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli. Hum Mol Genet. 2004 Jun 15;13(12):1249-55. doi: 10.1093/hmg/ddh136. Epub 2004 Apr 28.