Study for patients with Primary Hyperoxaluria and Severe Renal Impairment to evaluate the efficacy, safety and tolerability of DCR-PHXC
- Conditions
- Primary HyperoxaluriaMedDRA version: 23.0Level: PTClassification code 10084111Term: Primary hyperoxaluriaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2020-002826-97-DE
- Lead Sponsor
- Dicerna Pharmaceuticals Inc. (a Novo Nordisk Company)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 28
In order to be eligible to participate in this study, an individual must
meet all of the following criteria:
Age
1. Four age groups of participants will be enrolled:
a. adults and adolescents (aged = 12 years)
b. children 6 to 11 years of age
c. children 2 to 5 years of age and
d. infants and newborns from birth to < 2 years of age.
Type of Participant and Disease Characteristics
2. Documented diagnosis of PH1 confirmed by genotyping (historically
available genotype information is acceptable for study eligibility)
3. Estimated GFR at Screening < 30 mL/min normalized to 1.73 m2 BSA.
See Section 8.2.6.2 of the protocol for equations. For infants aged less
than 12 months, serum creatinine above the 97.5th percentile of a
healthy population
4. Mean of 2 plasma oxalate values > 20 µmol/L during Screening. See
Section 8.1.1 of the protocol for collection details.
5. For participants receiving hemodialysis or peritoneal dialysis, total
duration of hemodialysis or peritoneal dialysis must be less than or
equal to 24 months and hemodialysis or peritoneal dialysis regimen must
have been stable for at least 2 weeks prior to Screening.
Sex
7. Male or female
Male participants:
A male participant with a female partner of childbearing potential must
agree to use contraception, as detailed in Section 10.5.2, during the
treatment period and for at least 12 weeks after the last dose of study
intervention and refrain from donating sperm during this period.
Female participants:
A female participant is eligible to participate if she is not pregnant (see
Section 10.5.3), not breastfeeding, and at least one of the following
conditions applies:
Not a woman of childbearing potential (WOCBP) as defined in Section
10.5.1.1.
OR
A WOCBP who agrees to follow the contraceptive guidance in Section
10.5.2.2 for the 4 weeks prior to randomization, during the treatment
period, and for at least 12 weeks after the last dose of study intervention
and agrees to refrain from harvesting/freezing eggs during this period.
Contraceptive use by men or women should be consistent with local
regulations regarding the methods of contraception for those
participating in clinical studies.
Informed Consent/Assent
8. Participant (and/or participant's parent or legal guardian if
participant is a minor [defined as patient < 18 years of age, or younger
than the age of majority according to local regulations]) is capable of
giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF)
and in this protocol.
a. Adolescents (12 to < 18 years of age, or older than 12 years but
younger than the age of majority according to local regulations) must be
able to provide written assent for participation.
b. For children younger than 12 years of age, assent will be based on
local regulations.
Other
9. Affiliated with or is a beneficiary of a health insurance system (if
applicable per national regulations)
Are the trial subjects under 18? yes
Number of subjects for this age range: 21
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
An individual who meets any of the following criteria will be excluded from participation in this study:
Medical Conditions
1. Prior hepatic transplantation; or scheduled transplantation within 6 months of Day 1. Renal transplantation planned in the 6 months from Day 1. Prior renal transplantation is allowed.
2. Documented evidence of clinical manifestations of severe systemic oxalosis (including preexisting retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations)
3. Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially impact patient safety including, but not restricted to:
a. Severe intercurrent illness
b. Known causes of active liver disease/injury (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis)
c. Non-PH related conditions contributing to renal insufficiency
d. Physician concerns about intake of drugs of abuse or excessive alcohol intake, or history of excessive alcohol intake in the 2 years prior to enrollment (defined as = 21 units of alcohol per week in men and = 14 units of alcohol per week in women; where a unit” of alcohol is equivalent to a 12-ounce beer, 4-ounce glass of wine, or 1 ounce shot of hard liquor)
Prior/Concomitant Therapy
4. Use of an RNAi drug, other than DCR-PHXC, within the last 6 months
5. History of one or more of the following reactions to an oligonucleotide-based therapy:
a. Severe thrombocytopenia (platelet count = 100,000/µL)
b. Hepatotoxicity, defined as alanine transaminase (ALT) or aspartate transaminase (AST) > 3 times the upper limit of normal (ULN) and total bilirubin > 2 × ULN or international normalized ratio (INR) >1.5
c. Severe flu-like symptoms leading to discontinuation of therapy
d. Localized skin reaction from the injection (graded severe) leading to discontinuation of therapy
e. Coagulopathy/clinically significant prolongation of clotting time
Prior/Concurrent Clinical Study Experience
6. Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months or 5 times the half-life of the drug (whichever is longer) before Screening.
Diagnostic Assessments
7. Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender
8. Positive anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody test at Screening
Other Exclusions
9. Known hypersensitivity to DCR-PHXC or any of its ingredients
10. Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations detailed in Section 5.3.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method