Study for patients with Primary Hyperoxaluria and Severe Renal Impairment to evaluate the efficacy, safety and tolerability of DCR-PHXC

• Register: EUCTR
• Last refreshed on: 16 December 2024
• Main ID: EUCTR2020-002826-97-IT
• Date of registration: 07/06/2021
• Prospective Registration: No
• Primary sponsor: Dicerna Pharmaceuticals Inc.
• Public title: Study for patients with Primary Hyperoxaluria and Severe Renal Impairment to evaluate the efficacy, safety and tolerability of DCR-PHXC
• Scientific title: A Phase 2 Open-Label Study to Evaluate the Safety and Efficacy of DCRPHXC in Patients With Primary Hyperoxaluria Type 1 or 2 and Severe Renal Impairment, With or Without Dialysis - PHYOX 7: Safety & Efficacy of DCR-PHXC in patients with PH1/2 and ESRD
• Date of first enrolment: 12/05/2021
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002826-97
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, France, Germany, Italy, Romania, Spain, United Kingdom, United States

Contacts

• Name: Kerry Russell
• Affiliation: Dicerna Pharmaceuticals Inc

• Name: Kerry Russell
• Affiliation: Dicerna Pharmaceuticals Inc

Key inclusion & exclusion criteria

Inclusion criteria:
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, in sequence:
a. adults and adolescents (aged = 12 years; 6 participants)
b. children 6 to 11 years of age (2 participants)
c. children 2 to 5 years of age (2 participants) and
d. infants and newborns from birth to < 2 years of age (2 participants).
Type of Participant and Disease Characteristics
2. Documented diagnosis of PH1 or PH2, 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 for equations. For infants aged less than 12 months, serum creatinine above the 97th percentile of a healthy population (Boer et al., 2010)
4. Mean of 3 plasma oxalate values > 30 µmol/L during Screening
5. Less than 20% variation from the median Screening period Pox value
6. For participants receiving hemodialysis or peritoneal dialysis, total duration of hemodialysis or peritoneal dialysis must be less than or equal to 18 months and hemodialysis or peritoneal dialysis regimen must have been stable for at least 3 months prior to Screening.
Weight
7. Body weight of:
a. adults and adolescents aged = 12 years: = 31.0 kg
b. children 6 to 11 years of age: to be determined
c. children 2 to 5 years of age: to be determined
d. infants and newborns from birth to < 2 years of age: to be determined
Sex
8. 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 10.4.3), not breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) as defined in Section 10.4.1.1.
OR
A WOCBP who agrees to follow the contraceptive guidance in Section 10.4.2.2 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
9. 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
10. 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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65
Exclusion criteria:
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. Prior renal transplantation is allowed.
2. Known history of severe systemic oxalosis
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. 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary Hyperoxaluria
MedDRA version: 20.1 Level: PT Classification code 10020703 Term: Hyperoxaluria System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: Nedosiran
Product Code: [DCR-PHXC]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DCR-L1360
Current Sponsor code: DCR-PHXC
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 170-

Primary Outcome(s)

Main Objective: To characterize the safety of DCR-PHXC in participants with PH1 or PH2 and severe renal impairment, with or without hemodialysis or peritoneal dialysis

Secondary Objective: 1. To assess the efficacy of DCR-PHXC in lowering Pox in participants with PH1 or PH2 and severe renal impairment, with or without hemodialysis or peritoneal dialysis
2. To assess the multiple dose PK of DCR-PHXC and its metabolites in participants with PH1 or PH2 and severe renal impairment, with or without hemodialysis or peritoneal dialysis
3. To assess the effect of DCR-PHXC on the hemodialysis or peritoneal dialysis regimen of participants with PH1 or PH2 undergoing hemodialysis or peritoneal dialysis

Timepoint(s) of evaluation of this end point: The primary endpoint is safety and will be evaluated during the whole study

Primary end point(s): Incidence and severity of TEAEs and SAEs, and the change from Baseline in 12-lead ECG, physical examination findings, vital signs, and clinical laboratory tests

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The secondary endpoints evaluation will be based on:
- Change in Pox from Baseline to Day 180
- Change in the duration and number of weekly hemodialysis or peritoneal dialysis sessions

Secondary end point(s): 1. Change from Baseline in Pox
2. Plasma PK parameters for DCR-PHXC and its metabolites (e.g., Cmax and AUC, based on NCA or POP-PK analysis)
3. The change in the duration and number of weekly hemodialysis or peritoneal dialysis sessions from Baseline to Month 12 and quarterly
thereafter in the long-term extension

Secondary ID(s)

2020-002826-97-FR

NCT04580420

DCR-PHXC-204

Source(s) of Monetary Support

Dicerna Pharmaceuticals Inc

Ethics review

Status: Approved
Approval date: 12/05/2021
Contact: