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

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: EUCTR2018-003098-91-DE
• Lead Sponsor: Dicerna Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-12-18
• Last Update Posted: 26 July 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Age
1.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 PH1 or PH2, confirmed by genotyping (historically available genotype information is acceptable for study eligibility)
3. 24-hour Uox excretion = 0.7 mmol (adjusted per 1.73 m2 BSA in participants < 18 years of age) in both collections performed in the screening period. At least 12 participants must have at least one 24 hour Uox excretion = 1.6 mmol (adjusted per 1.73 m2 BSA in participants aged < 18 years).
4. Less than 20% variation between the two 24-hour urinary creatinine measurements in the screening period. Individuals who do not achieve < 20% variation between the 2 screening values may undergo a second round of urine collection. An extra 7 calendar days may be added to the screening window for participants to complete a second round of urine collection. Should potential participants again fail to achieve the within -20% variation, they will be excluded from participation.
5. Estimated GFR at screening = 30 mL/min normalized to 1.73 m2 BSA, calculated using the CKD-EPI equation in participants aged = 18 years (Levey & Stevens, 2010) or the 2012 multivariate equation by Schwartz in participants aged 6 to 17 years (Schwartz et al., 2012).
Sex
6. 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 1 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
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 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: 12
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
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 or anticipating requirement for dialysis during the study period
3. Plasma oxalate > 30 µmol/L
4. 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)
5. 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 or transaminase elevation (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)
d.History of serious mental illness that includes, but is not limited to, schizophrenia, bipolar disorder, or severe depression requiring hospitalization or pharmacological intervention
e.Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological diseases, including dermatological including rash, severe eczema or dermatitis, or connective tissue diseases or disorders

Prior/Concomitant Therapy
6. Use of an RNA interference (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 alanine aminotransferase (ALT) or aspartate aminotransferase (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
8. Participants 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.

Prior/Concurrent Clinical Study Experience
9. Participation in any clinical study in which they received an investigational medicinal product (IMP) within 4 months before Screening
a. For IMPs with the potential to reduce urine and/or plasma oxalate concentrations, these concentrations must have returned to historical baseline levels prior to Screening

Diagnostic assessments
10. Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender
11. Positive screening for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies. If participant has been tested in the past 3 months, medical record documentation of this testing can be used for screening. Viral serology testing not required in participants < 18 years of age.
12. Positive urine

Study & Design

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