Primary:* Evaluate the long-term safety of multiple doses of ALN-GO1 in patients with PH1.Secundary:* Evaluate the pharmacodynamic (PD) effect of ALN-GO1 on urinary oxalate excretion* Characterize the effect of ALN-GO1 on markers of renal function.…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study outcome is the incidence of adverse events (AEs)
Secondary outcome
* Change in 24-hour urinary oxalate corrected for body surface area (BSA) over
time
* Change in 24-hour urinary oxalate: creatinine ratio over time
* Change estimated glomerular filtration rate (eGFR) over time
Exploratory
* Describe the effects of ALN-GO1 on other safety parameters, including
assessments of vital signs, electrocardiograms (ECGs), renal ultrasounds,
clinical laboratory parameters, and physical examinations.
* Assess ALN-GO1 plasma PK parameters including maximum plasma concentration
(Cmax), time to maximum plasma concentration (tmax), elimination half-life
(t1/2), area under the concentration-time curve (AUC), fraction of drug
excreted in urine (Fe), apparent clearance (CL/F), and apparent volume of
distribution (V/F).
* Change from Baseline over the course of the study in the following PD
parameters:
- Urinary glycolate excretion
- Plasma oxalate concentration
- Plasma glycolate concentration
- Spot urinary oxalate:creatinine ratio
* Incidence of ADA.
Background summary
Currently, there are no approved therapies for the treatment of PH1. Disease
management is based on supportive measures, including high fluid intake,
potassium citrate (to increase urinary oxalate solubility), Vitamin B6, and
treatment of complications such as urinary tract stones and infections.
Therefore, there is a high unmet medical need for additional treatments for
patients with PH1.
Study objective
Primary:
* Evaluate the long-term safety of multiple doses of ALN-GO1 in patients with
PH1.
Secundary:
* Evaluate the pharmacodynamic (PD) effect of ALN-GO1 on urinary oxalate
excretion
* Characterize the effect of ALN-GO1 on markers of renal function.
Exploratory:
* Characterize the pharmacokinetics (PK) of ALN-GO1
* Evaluate the PD effect of ALN-GO1 on urinary glycolate excretion, plasma
oxalate concentration, plasma glycolate concentration, and urine
oxalate:creatinine ratio.
* Evaluate the incidence of anti-drug antibodies (ADA).
Study design
This is a phase 2, multicenter, open-label, extension study to evaluate the
long-term administration of ALN-GO1 in patients with primary hyperoxaluria type
1.
Intervention
ALN-GO1 is a synthetic, double-stranded small interfering RNA oligonucleotide
directed against hydroxyacid oxidase 1 mRNA that is covalently linked to a
ligand containing 3 N-acetylgalactosamine residues. ALN-GO1 will be supplied as
a sterile solution for subcutaneous (SC) injection at a targeted concentration
of 200 mg/mL.
Study burden and risks
ALN-GO1 is designed to reduce hepatic production of oxalate. The potential
benefit of this treatment is the amelioration of the clinical course of PH1 in
patients across the spectrum of disease, irrespective of age and disease stage;
however, patients with PH1 in this study may not receive treatment for a
sufficient duration, or at an adequate dose, to experience clinical benefit.
The potential benefit to children enrolled in this study includes possible
reduction in oxalate production during the study period, which may have a
temporarily ameliorating effect on their disease. In addition, experience in
children with this disease under carefully controlled conditions will provide
data that may enhance the future development of this therapeutic. Moreover,
since evaluation of safety and PD effects in children will be important in the
design of future studies, it is considered important and appropriate to enroll
children in the current study.
Third Street 300
Cambridge 02142 MA
US
Third Street 300
Cambridge 02142 MA
US
Listed location countries
Age
Inclusion criteria
1. Enrollment within 12 months of completion of Study ALN-GO1-001 and in the
opinion of the investigator, tolerated the study drug
2. If taking vitamin B6 (pyridoxine), willing to remain on a stable regimen for
the study duration
3. Women of child-bearing potential must have a negative pregnancy test, cannot
be breast feeding, and must be willing to use a highly effective method of
contraception from 14 days before first dose and throughout study participation
until the completion of the follow-up period.
4. Willing and able to comply with the study requirements and to provide
written informed consent and assent in the case of patients under the age of
legal consent, per local and national requirements.
Exclusion criteria
1. Any uncontrolled or serious disease, or any medical or surgical condition
(with the exception of PH1) that may either interfere with participation in the
clinical study, and/or put the patient significant risk (according to the
Investigator*s judgment) if he/she participates in the clinical study
2. An underlying known disease or surgical or medical condition (with the
exception of PH1) that in the opinion of the investigator might interfere with
the interpretation of the clinical study results
3. Requirement for chronic dialysis
4. Triplicate 12-lead ECG with clinically significant abnormalities at Baseline
visit, at the discretion of the investigator
5. Echo assessment of abnormal left ventricular systolic function, defined as
left ventricular ejection fraction <55% at Screening
6. Abnormal for aspartate aminotransferase (AST)/alanine aminotransferase (ALT)
and any other clinical safety laboratory result considered clinically
significant and unacceptable by the Investigator at Baseline, at discretion of
investigator
7. Legal incapacity or limited legal capacity at Screening of patient, parent,
or legal guardian
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 | EUCTR2016-003134-24-NL |
| CCMO | NL62494.000.17 |