2-part study of DCR-PHXC in healthy volunteers and in primary hyperoxaluria patients

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: EUCTR2017-003534-89-GB
• Lead Sponsor: Dicerna Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-16
• Study Completion: 2019-11-19
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

For Part A & Part B of the study:

1.Subject understands the full nature and purpose of the study, including possible risks and side effects, and is willing and able to comply with all study procedures and restrictions.
2.Females and males and their female partner(s) of childbearing potential must be willing to use a highly effective and approved contraceptive method (s) from the date of informed consent until 12 weeks after the last dose of Investigational Medicinal Product (IMP). A highly effective method of contraception is defined as fulfilling at least one of the following:
a.Strict abstinence: When this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.]
b.Surgically sterile (having undergone one of the following surgical procedures: hysterectomy, bilateral tubal ligation, bilateral oophorectomy, or bilateral salpingectomy) and at least 6 weeks post-sterilization.
c.Combined hormonal oral contraceptive (estrogen and progesterone), implanted, or injectable contraceptive on a stable dose for at least one month prior to the screening visit plus a barrier method. Combined hormonal contraception is considered a highly effective method of contraception only if it is associated with inhibition of ovulation. If associated with inhibition of ovulation, progesterone-only hormonal contraception is also considered a highly effective method of contraception.
d.Intrauterine devices plus condoms. Hormonal intra-uterine device (IUD) inserted at least 1 month prior to the screening visit.
e.Double-barrier methods [e.g., Condom and Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository]. Of note, a female condom and a male condom, or two male condoms, should not be used together as friction between the two can result in either product failing.
f.Vasectomized partner (at least 6 months post-procedure) prior to the screening visit.
3.Postmenopausal females: defined as 12 months with no menses prior to screening and a serum follicle stimulating hormone (FSH) > 26 IU/L at Screening visit.
4.For females: a negative pregnancy test at screening and Day 0 visit.

PART A specific
1.Male or female subjects between 18 and 55 years of age, inclusively.
2.Subject must have a body mass index (BMI) between 19.0-32 kg/m2, inclusive.
3.Non-smokers, at least 1 month tobacco free, and willing to remain tobacco free through EOS. Subjects must also be free from nicotine-containing products (e.g. nicotine patch.)
4.Subjects must be otherwise healthy. Healthy status will be defined based on the opinion of the principal investigator (PI) by the absence of evidence of any clinically significant, active, or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, serology, and urinalysis.
5.Subjects must have hematology and clinical chemistry tests and urine analyses within the normal range, unless abnormalities are classified as Not Clinically Significant (NCS) by the investigator or qualified designee. Liver panel tests must be normal. Retests may be conducted one time for liver panel results.

Part B specific
1.Male or female, at least 6 years of age at the time of obtaining informed consent.
2.Documented diagnosis of PH1 or PH2, confi

Exclusion Criteria

Part A and Part B:
1.History of alcohol consumption exceeding more than 21 units in males, 14 units in females, per week as determined by the Investigator.
2.Males with female partners who are planning to attempt to become pregnant during this study or within 90 days after last dosing of IMP.

Part A specific:
1.Presence of any medical condition or co-morbidities that would interfere with study compliance or data interpretation or potentially impact subject safety including, but not restricted to:
a.severe intercurrent illness
b.routine vaccination within 30 days prior to dosing and through EOS visit
c.known causes of active liver disease/ injury or transaminase elevation (e.g., alcoholic liver disease, Nonalcoholic fatty liver disease/ steatohepatitis [NAFLD/NASH])
d.physician concerns about excess alcohol consumption
e.routine or chronic use of more than 3 grams of paracetamol daily.
2.History of kidney stones.
3.Women who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after last dosing of IMP.
4.Use of any investigational agent within 90 days before the first dose of study medication. If a subject has participated in prior siRNA or antibody studies, a washout period of at least 6 months before the first administered dose in this study is required.
5.Use of tobacco products within 30 days prior to dosing and through EOS visit.
6.Strenuous activity, sunbathing, and contact sports within 48 hours (2 days) prior to dose administration and through to the EOS visit or Day 29.
7.History of donation of more than 450 mL of blood within 90 days prior to dosing in the clinical research center or planned donation less than 30 days after receiving IMP.
8.Plasma or platelet donation within 7 days of dosing and throughout the entire study.
9.Positive screening test for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies. If subject has been tested in the past 3 months, historical data may be used.
10.History of one or more of the following reactions to an oligonucleotide-based therapy
a.Severe thrombocytopenia
b.Hepatotoxicity
c.Severe flu-like symptoms leading to discontinuation of therapy
d.Localized skin reaction from the injection (Grade 3 or higher) leading to discontinuation of therapy.
e.Coagulopathy/ clinically important prolongation of clotting time

Part B specific
1.Prior renal and/or hepatic transplantation.
2.Currently receiving dialysis.
3.Documented evidence of clinical manifestations of systemic oxalosis.
4.Participation in any clinical study where they received an investigational medical product within 4 months before enrollment. For IMPs with the potential to reduce Uox and or plasma oxalate, these concentrations must have returned to historical baseline levels.
a.If patient participated in an earlier cohort in this study (DCR-PHXC-101), a minimum of 8 weeks must have elapsed prior to re-enrollment and urinary oxalate excretion must have returned to = 80% of baseline.
5.Presence of any medical condition or co-morbidities that would interfere with study compliance or data interpretation or potentially impact subject safety including, but not restricted to:
a. severe intercurrent illness
b.routine vaccination within 30 days prior to dosing and through EOS visit
c.known causes of active liver disease/ injury or transaminase elevation (e.g., alcoholic l

Study & Design

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