Primary Objective:- To determine the safety and tolerability of DCR-PH1 administered via intravenous (IV) infusion to patients with PH1.Secondary Objective:- To study the pharmacokinetics (PK) of DCR-PH1- To study the pharmacodynamics (PD) effects…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Autosomal recessive disorder
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and tolerability as determined by number of subjects with adverse events
Secondary outcome
1) Determination of pharmacokinetics parameters
2) Change in plasma levels from baseline (BL) to each time point of oxalate and
glycolate
3) Change in urine levels from baseline (BL) of oxalate, oxalate to creatinine
ratio and glycolate
Background summary
DCR-PH1 is intended to minimize the excessive production of oxalate in patients
diagnosed with PH1 by blocking the production of glyoxylate, a key precursor
for the production of oxalate in the liver.
The SAD (Part A) portion of Study DCR-PH1 is designed to identify doses of
DCR-PH1 that are safe, tolerated and suitable for subsequent clinical
assessment in the MAD (Part B) portion of the study. Once the Part A (SAD
portion) maximum tolerated dose (MTD) has been established, all
available clinical and nonclinical data will be summarized and submitted to
regulatory authorities and ethics committees, together with a protocol
amendment to support dosing in Part B (MAD portion) of the study.
The MAD portion of the study will provide additional safety and tolerability
information as well as better characterization of the pharmacokinetic (PK) and
PD effects of multiple DCR-PH1 doses.
Study objective
Primary Objective:
- To determine the safety and tolerability of DCR-PH1 administered via
intravenous (IV) infusion to patients with PH1.
Secondary Objective:
- To study the pharmacokinetics (PK) of DCR-PH1
- To study the pharmacodynamics (PD) effects of DCR-PH1 including, but not
limited to changes in plasma and urine oxalate and glycolate levels
Additional secondary objectives for Part B are:
- To study clinical and radiological changes related to hyperoxaluria during
treatment with DCR-PH1
- To study the quality of life (QOL) in patients during treatment with DCR-PH1
Study design
This is a single-arm, open-label, dose escalation study of DCR-PH1 designed to
define a safe and tolerable dose of DCR-PH1 for patients with PH1.
Intervention
For Part A (SAD):
Dose Level (Cohort) Dose (mg/kg) Percent increase
1
0.05 -
2 0.1
100%
3 0.2
100%
4 0.4
100%
5
0.7 75%
6
1.0 50%
Study burden and risks
DCR-PH1 has not been studied in humans. Since information on side effects has
been obtained only from studies in animals, little is known about the side
effects it may cause in humans. There have, however, been studies in humans of
drugs that are similar to DCR-PH1 (because they have the same type of *coating*
around the active part of the drug), and the side effects from those studies
are listed in the Patient Information Leaflet.
There are certain risks and discomforts that may be associated with this
research:
There is a slight risk of side effects from the routine blood tests that will
be required throughout the study. There could be pain, swelling, and/or
bruising at the site where you get your blood drawn, as well as possible
inflammation of the vein or an infection at this site.
Cambridgepark Drive 87
MA 02140 Cambridge
US
Cambridgepark Drive 87
MA 02140 Cambridge
US
Listed location countries
Age
Inclusion criteria
- Diagnosis of PH1, confirmed by genotyping for homozygosity or compound heterozygosity in
the AGXT gene (historically available genotype information is acceptable for study eligibility).
- 24-hour urine oxalate excretion * 0.7 mmol per 1.73 m2 body surface area (BSA).
- Estimated glomerular filtration rate * 40 mL/min normalized to 1.73 m2 BSA calculated using
the Modification of Diet in Renal Disease (MDRD) formula in adults (age * 18 years).
Exclusion criteria
- Prior renal and/or hepatic transplantation.
- History of clinical signs and symptoms of systemic oxalosis other than nephrolithiasis or
nephrocalcinosis.
- Participation in any clinical study involving administration of any investigational drug within
the 30 days before enrollment
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR201500314251-NL |
| CCMO | NL54981.000.15 |