Study for patients with Primary Hyperoxaluria to evaluate the Long-Term Safety and Efficacy of DCR-PHXC Solution for Injectio

Phase 1

• Conditions: Primary Hyperoxaluria; MedDRA version: 20.1Level: PTClassification code 10020703Term: HyperoxaluriaSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2018-003099-10-DE
• Lead Sponsor: Dicerna Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-12-12
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:
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, or is the sibling of a participant who successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC. Siblings must be younger than 18 years of age and must meet all other eligibility criteria.
a. For participants rolling over from a multidose study of DCR-PHXC, enrollment should occur within a window of 25 to 60 days from the last dose of study intervention.
4. Estimated GFR at screening = 30 mL/min normalized to 1.73 m2 BSA calculated using the CKD-EPI formula in participants aged = 18 years (Levey & Stevens, 2010), or the formula by Schwartz in participants aged 6 to 17 years (Schwartz et al., 2009; National Kidney Foundation, 2002). In Japan, the formula by Uemura et al. will be used for participants aged 6 to 17 years (Uemura et al., 2014).
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: 20
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

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:
Medical Conditions
1. Prior renal or hepatic transplantation; or planned transplantation within the study period
2. Currently receiving dialysis
Documented evidence of clinical manifestations of systemic oxalosis (including pre-existing retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations)Prior/Concomitant Therapy
3. Routine or chronic use of more than 3 grams of acetaminophen/paracetamol daily
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 aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 × 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
6. Participants receiving pyridoxine (vitamin B6) 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.
Prior/Concurrent Clinical Study Experience
7. Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months 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.
Other Exclusions
8. Known hypersensitivity to DCR PHXC or any of its ingredients
9. Inability or unwillingness to comply with the specified study procedures, including collection of 24-hour urine samples, and the lifestyle considerations detailed in Section 5.3.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified