Study for patients with Primary Hyperoxaluria to evaluate the Long-Term Safety and Efficacy of DCR-PHXC Solution for Injectio
- Conditions
- Primary HyperoxaluriaMedDRA version: 20.1Level: PTClassification code 10020703Term: HyperoxaluriaSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-003099-10-IT
- Lead Sponsor
- Dicerna Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 50
ROLL-OVER PARTICIPANTS AND THEIR PEDIATRIC SIBLINGS
Age
1. Participant must be at least 6 years of age, at the time of signing the informed consent/assent.
Type of Participant and Disease Characteristics
2. Documented diagnosis of PH, confirmed by genotyping (historically available genotype information is acceptable for study eligibility)
3. Participant successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR-PHXC.
a. For participants rolling over from Study DCR-PHXC-101, a minimum 12 weeks must have elapsed from dosing in DCR-PHXC-101 and 24-hour Uox excretion must have returned to =80% of study DCR-PHXC-101 baseline.
4. Estimated GFR at screening = 30 mL/min normalized to 1.73 m2 BSA calculated using the Modification of Diet in Renal Disease (MDRD) formula in participants aged > 16 years, or the formula by Schwartz in participants aged 6 to 16 years (Levey et al., 1999; Schwartz et al., 2009; National Kidney Foundation, 2002).
Sex
5. Male or female
Male participants:
A male participant with a female partner of childbearing potential must agree to use contraception, as detailed in Section 10.4.2, 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 10.4.1), not breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) as defined in Section 10.4.1
OR
A WOCBP who agrees to follow the contraceptive guidance in Section 10.4.2 during the treatment period and for at least 12 weeks after the last dose of study intervention.
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
6. 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.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
ROLL-OVER PARTICIPANTS&PED SIBLINGS
1.Prior renal or hepatic transpl;or planned transpl within study period
2.Currently receiving dialysis
3.Documented evidence of clinical manifestations of systemic oxalosis
4.Routine or chronic use of more than 3gr of acetaminophen/paracetamol daily
5.Use of an RNAi drug (other than DCR-PHXC)within last 6months
6.History of 1 or more of the following reactions to an oligonucleotide-based therapy: a. severe thrombocytopenia (platelet count =100,000/µL)b.hepatotoxicity, defined as(ALT or AST >3×the ULN) and (total bilirubin >2×ULN or 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
7.Particip receiving pyridoxine (vitB6)must have been at a stable dose for at least 4weeks prior to Day1 and must be willing to remain on the same stable dose throughout the study
8.Participation in any clinical study in which they received an IMP)other than DCR-PHXC within 4months before Screening. a.For IMPs(other than DCR-PHXC)with the potential to reduce urine
and/or plasma oxalate concentrations, these concentrations must have returned to historical baseline levels prior to Screening
9.Plasma oxalate > 30µmol/LNote:For participants rolling over from a 6-month multidose study of
DCR-PHXC,plasma oxalate value from either Day150 or Day180(EOS) visit may be used for screening
10.Known hypersensitivity to DCR-PHXC or any of its ingredients
11.Inability or unwillingness to comply with study procedures
6-11-YRs-OLD CHILDREN NOT PREVIOUSLY ENROLLED IN A STUDY OF DCR-PHXC
1.Prior renal or hepatic transpl; or planned transpl within study period
2.Currently receiving dialysis or anticipating requirements for dyalisis during study period
3.Documented evidence of clinical manifestations of systemic oxalosis
4.Presence of any condition or comorbidities that would interfere with study compliance
or data interpretation or potentially impact study participant safety including, but not restricted to:a.severe intercurrent illness b. known causes of active liver disease/injury or transaminase elevation b.known causes of active liver disease/injury or transaminase elevation c.history of serious mental illness that includes, but not limited to,schizophrenia,bipolar disorder, or severe depression requiring hospitaliz or pharmacol intervention d.clinically relevant history or presence of cardiovas, respir,gastrointes,hematolog,lymphatic,neurolog,musculoskel,genitourin,immunologi diseases,including dermatolog,or connective tissue diseases or disorders
5.Routine or chronic use of more than 3gr of acetaminophen/paracetamol daily
6.Use of an RNAi drug within the last 6 months
7.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 ALT or AST > 3 × ULN and total bilirubin >2×ULN or 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
8.Particip receiving pyridoxine must have been at a stable dose for at least 4 weeks prior to Day 1 and must be willing to remain on the same stable dose throughout the study.
9.Participation in any clinical study in which th
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