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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dicerna Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

8 Apr 2021 → ongoing

Decision date (initial)

2024-09-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Dicerna Pharmaceuticals, Inc., a wholly owned subsidiary of Novo Nordisk

External identifiers

EU CT number

2024-512259-19-00

EudraCT number

2020-002826-97

ClinicalTrials.gov

NCT04580420

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the efficacy of DCR-PHXC in lowering Pox in participants with PH1 and severe renal impairment, with or without hemodialysis or peritoneal dialysis.

Secondary objectives 7

1. To assess the efficacy of DCR-PHXC in lowering Pox in participants with PH1 and severe renal impairment, with or without hemodialysis or peritoneal dialysis.
2. To characterize the safety of DCR-PHXC in participants with PH1 and severe renal impairment, with or without hemodialysis or peritoneal dialysis
3. To assess the multiple dose PK of DCR PHXC in participants with PH1 and severe renal impairment, with or without hemodialysis or peritoneal dialysis
4. To assess the effect of DCR-PHXC on the hemodialysis or peritoneal dialysis regimen of participants with PH1 undergoing hemodialysis or peritoneal dialysis
5. To evaluate the effect of DCR PHXC on stone burden in participants with PH1 and severe renal impairment, with or without hemodialysis or peritoneal dialysis
6. To evaluate the effect of DCR PHXC on nephrocalcinosis score
7. To evaluate the effect of DCR PHXC on cardiac oxalosis

Conditions and MedDRA coding

Primary Hyperoxaluria

Regulatory references

Scientific advice from competent authorities

Bundesverband Der Arzneimittel-Hersteller e.V., European Medicines Agency, Medicines And Healthcare Products Regulatory Agency

EMA paediatric investigation plan (PIP)

EMEA-002493-PIP01-18

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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.
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. 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.
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.
6. Male or female.
7. 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.
8. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP), 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.
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.
10. 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.
11. For children younger than 12 years of age, assent will be based on local regulations.
12. Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations).

Exclusion criteria 10

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.
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.
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.
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 detailed in Section 5.3.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The absolute and percent change in Pox from Baseline to Day 180.

Secondary endpoints 5

1. Absolute and percent change in Pox from Baseline to maximum reduction through Day 180.
2. Change in the hemodialysis or peritoneal dialysis regimen.
3. Change in stone burden identified via ultrasound from Baseline to Day 180.
4. Change in nephrocalcinosis score.
5. Change in cardiac oxalosis.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dicerna Pharmaceuticals Inc.

Sponsor organisation

Dicerna Pharmaceuticals Inc.

Address

75 Hayden Avenue

City

Lexington

Postcode

02421-7994

Country

United States

Scientific contact point

Organisation

Dicerna Pharmaceuticals Inc.

Contact name

EU Submission Hub

Public contact point

Organisation

Dicerna Pharmaceuticals Inc.

Contact name

EU Submission Hub

Third parties 10

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 79 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications