RECRUITING

Safety & Efficacy of DCR-PHXC in Patients With PH1 and ESRD

Conditions

Primary Hyperoxaluria Type 1 End Stage Renal Disease PH1 ESRD

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The aim of this study is to evaluate DCR-PHXC in participants with PH1 and severe renal impairment, with or without dialysis.

Official Title

A Phase 2 Open-Label Study to Evaluate the Safety and Efficacy of DCR-PHXC in Patients With Primary Hyperoxaluria Type 1 and Severe Renal Impairment, With or Without Dialysis

Quick Facts

Study Start:2021-04-15

Study Completion:2032-01-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04580420

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Four age groups of participants will be enrolled: 1. adults and adolescents (aged ≥ 12 years) 2. children 6 to 11 years of age 3. children 2 to 5 years of age 4. infants and newborns from birth to \< 2 years of age 2. . Documented diagnosis of PH1, confirmed by genotyping 3. Estimated GFR at Screening \<30mL/min normalized to 1.73m\^2 BSA 4. Mean of 2 Plasma Oxalate \>20μmol/L during screening 5. For participants receiving hemodialysis or peritoneal dialysis total duration of hemodialysis or peritoneal dialysis must be less than 24 months and hemodialysis or peritoneal dialysis regimen must have been stable for at least 2 weeks prior to Screening. 6. Male or Female 1. Male participants: * A male participant with a female partner of childbearing potential must agree to use contraception 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. 2. Female participants: * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * OR * A WOCBP who agrees to follow the contraceptive guidance 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. 3. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 7. 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 requirement and restrictions listed in the informed consent form (ICF) and in the protocol. 1. 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. 2. For children younger than 12 years of age, assent will be based on local regulations 8. Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations)	1. Prior hepatic transplantation; or scheduled transplantation within 6 months of 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: 1. Severe intercurrent illness 2. Known causes of active liver disease/injury (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis) 3. Non-PH related conditions contributing to renal insufficiency 4. 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 1ounce shot of hard liquor) 4. Use of an RNAi drug, other DCR-PHXC, within the last 6 months 5. History of one or more of the following reactions to an oligonucleotide-based therapy: 1. Severe thrombocytopenia (platelet count ≤ 100,000/µL) 2. 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 3. Severe flu-like symptoms leading to discontinuation of therapy 4. Localized skin reaction from the injection (graded severe) leading to discontinuation of therapy 5. Coagulopathy/clinically significant prolongation of clotting time 6. Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months before Screening. 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 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

Inclusion Criteria

Exclusion Criteria

1. Four age groups of participants will be enrolled:
1. adults and adolescents (aged ≥ 12 years)
2. children 6 to 11 years of age
3. children 2 to 5 years of age
4. infants and newborns from birth to \< 2 years of age
2. . Documented diagnosis of PH1, confirmed by genotyping
3. Estimated GFR at Screening \<30mL/min normalized to 1.73m\^2 BSA
4. Mean of 2 Plasma Oxalate \>20μmol/L during screening
5. For participants receiving hemodialysis or peritoneal dialysis total duration of hemodialysis or peritoneal dialysis must be less than 24 months and hemodialysis or peritoneal dialysis regimen must have been stable for at least 2 weeks prior to Screening.
6. Male or Female
1. Male participants:
* A male participant with a female partner of childbearing potential must agree to use contraception 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.
2. Female participants:
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
* OR
* A WOCBP who agrees to follow the contraceptive guidance 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.
3. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
7. 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 requirement and restrictions listed in the informed consent form (ICF) and in the protocol.
1. 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.
2. For children younger than 12 years of age, assent will be based on local regulations
8. Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations)

1. Prior hepatic transplantation; or scheduled transplantation within 6 months of 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:
1. Severe intercurrent illness
2. Known causes of active liver disease/injury (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis)
3. Non-PH related conditions contributing to renal insufficiency
4. 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 1ounce shot of hard liquor)
4. Use of an RNAi drug, other DCR-PHXC, within the last 6 months
5. History of one or more of the following reactions to an oligonucleotide-based therapy:
1. Severe thrombocytopenia (platelet count ≤ 100,000/µL)
2. 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
3. Severe flu-like symptoms leading to discontinuation of therapy
4. Localized skin reaction from the injection (graded severe) leading to discontinuation of therapy
5. Coagulopathy/clinically significant prolongation of clotting time
6. Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months before Screening.
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
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

Contacts and Locations

Study Contact

Novo Nordisk

CONTACT

(+1) 866-867-7178

clinicaltrials@novonordisk.com

Principal Investigator

Clinical Transparency (dept. 2834)

STUDY_DIRECTOR

Novo Nordisk A/S

Study Locations (Sites)

Clinical Trial Site

San Francisco, California, 94143

United States

Clinical Trial Site

Boston, Massachusetts, 02115

United States

Clinical Trial Site

Rochester, Minnesota, 55905

United States

Clinical Trial Site

New York, New York, 10016

United States

Collaborators and Investigators

Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Clinical Transparency (dept. 2834), STUDY_DIRECTOR, Novo Nordisk A/S

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-04-15

Study Completion Date2032-01-30

Study Record Updates

Study Start Date2021-04-15

Study Completion Date2032-01-30

Terms related to this study

Keywords Provided by Researchers

PH1
ESRD

Additional Relevant MeSH Terms

Primary Hyperoxaluria Type 1
End Stage Renal Disease