Pharmacokinetics and Safety Study of Single and Multiple Oral Doses Prodarsan™ in Patients With Cockayne Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01142154
• Date of registration: 20/05/2010
• Prospective Registration: Yes
• Primary sponsor: DNage B.V.
• Public title: Pharmacokinetics and Safety Study of Single and Multiple Oral Doses Prodarsan™ in Patients With Cockayne Syndrome
• Scientific title: A Phase I/II Crossover Study To Evaluate and Compare the Pharmacokinetics of a Single IV Dose of D-Mannitol (Osmitrol®10%) to Single and Multiple, Escalating Doses of Liquid, Oral Prodarsan™ in Patients With Cockayne Syndrome
• Date of first enrolment: June 2010
• Target sample size: 5
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01142154
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Edward Neilan, MD
• Affiliation: Children's Hospital Boston

Key inclusion & exclusion criteria

Inclusion Criteria:

- Parents or legal guardian(s) of the pediatric patient with CS must be willing and
able to give written Informed Consent. Informed Assent will be offered to children
who can understand and participate in the Informed Assent process.

- Diagnosis of CS confirmed by one of the following laboratory diagnostic test results:

- Demonstration by molecular diagnostic analyses of two mutations in either the
ERCC6 gene or the ERCC8 gene, wherein both mutations are either known to be
pathogenic or are obviously detrimental (including nonsense or frameshift
mutations, mutations of "invariant" splice site consensus signals, or large
deletions/rearrangements); OR

- A pattern of DNA repair responses in patient's cultured skin fibroblast cells
indicative of a specific deficiency of transcription-coupled DNA nucleotide
excision repair after irradiation with ultraviolet light, namely a significant
deficiency of cellular survival (and/or "recovery of ribonucleic acid [RNA]
synthesis," if that has been specifically measured) coupled with a normal test
for "unscheduled DNA synthesis" OR

- Decreased cell survival and/or "recovery of RNA synthesis" in UV-irradiated
patient's skin fibroblast cultures and rescue of these parameters by fusion to
reference cell lines with known NER defects (functional complementation
analysis) OR

- Quantitative RT-PCR to quantify mRNA levels of CS-A and CS-B transcripts.

- Weight inclusive of 10 kg to 25 kg.

- Male or female, inclusive of two (2) to ten (10) years of age.

- Clinically acceptable hematocrit as judged by the Principal Investigator (PI).

- The investigator has the opinion that the patient and caregiver are willing and able
to comply with protocol requirements.

Exclusion Criteria:

- Any concurrent illness (other than related to CS), disability or clinically
significant abnormality, including laboratory tests, that may affect the
interpretation of the PK or safety data or prevent the patient from safely completing
the assessments required by the protocol as judged by the investigator. Such
conditions include, but are not limited to:

- Ascites or generalized edema.

- Nephrotic syndrome or history of abnormal kidney function.

- Clinically significant thyrotoxicosis.

- Known history of hyperprolinemia.

- Clinically significant dehydration as judged by the investigator

- Severely compromised venous access.

- Presence of an external ventricular, abdominal, or chest drain.

- Subjects due to receive radioiodine therapy, two (2) weeks before or two (2) weeks
following the study period.

- Participation in another PK or treatment clinical study within thirty (30) days prior
to signing and dating of Informed Consent/Assent Form for this study.

- As judged by the investigator, clinical features present at the time of initial
screening, that are associated with the terminal phases of the natural progression of
CS, indicating that safe travel and completion of the study and its assessments are
unlikely, including any of the following:

- Continuous or intermittent dependence on supplemental oxygen at home during the
six (6) months prior to enrollment in this study; OR

- Two or more hospitalizations due to pneumonia, during the twelve (12) months
prior to enrollment in this study; OR

- A documented, net weight loss of at least 10%, which has not been recovered, and
which includes a significant net weight loss (beyond the estimated error of the
measurement) over the most recent 6 months despite intensive nutritional support
including the use of gastrostomy tube feedings.

- Known hypersensitivity to any of the components found in Prodarsan, D-mannitol,
iohexol or iodine compounds.

- History of clinically significant drug sensitivity or allergic reaction such as
anaphylaxis.



Age minimum: 2 Years
Age maximum: 10 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Cockayne Syndrome

Intervention(s)

Drug: Prodarsan

Primary Outcome(s)

Evaluate and compare the pharmacokinetics of D-mannitol following a single IV dose of Osmitrol to single and multiple oral doses of Prodarsan in pediatric patients with Cockayne Syndrome [Time Frame: 6 months]

Secondary Outcome(s)

Evaluate the safety and tolerability of administering oral Prodarsan in CS patients over a six (6) to eight (8) day period, including dose escalation to reach a Target Dose [Time Frame: 6 months]

Secondary ID(s)

MP1104-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors