NL-OMON46435Not yet recruitingNot Applicable
A Placebo-Controlled, Single-Blind, Single-Center Phase 1 Study in Normal Healthy Volunteers and Open-Label Multi Center Study in Patients with Primary Hyperoxaluria to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of DCR PHXC Solution for Injection (subcutaneous use) - A 2-part study in NHV and PH patients
Dicerna Pharmaceutical Inc0 sites5 target enrollmentStarted: TBDLast updated:
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 5
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional
Eligibility Criteria
- Ages
- 18 to 99 (—)
Inclusion Criteria
- •PH patients must meet all of the following criteria to be eligible for participation in this study.
- •1. Patient
- •a. Understands the full nature and purpose of the study, including possible risks and side effects.
- •b. Is willing and able to comply with all study procedures including collection of 24-hr urine samples.
- •c. Provides informed consent.
- •2. Male or female, at least 18 years of age at the time of obtaining informed consent. ;3. Documented diagnosis of PH1 or PH2, confirmed by genotyping (historically available genotype information is acceptable for study eligibility).
- •4. 24-hr urine oxalate excretion >=0.7 mmol on at least one of the two assessments conducted in the screening period, with less than 30% variation between both oxalate measurements.
- •5. eGFR >=30 mL/min normalized to 1.73 m2 BSA calculated using the Modification of Diet in Renal Disease (MDRD) formula (Levey et al., 1999; National Kidney Foundation, 2002).
- •6. Males, female patients of childbearing potential and female partners of male patients 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 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 1 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 IUD inserted at least 1 month prior to the screening visit.
- •e. Vasectomized partner (at least 6 months post-procedure) prior to the screening visit.
- •f. Postmenopausal females: defined as 12 months with no menses prior to screening and a serum FSH >26 IU/L at screening. ;7. For WOCP: a negative pregnancy test at screening and Day 0 ;8. Patients with PH1 receiving pyridoxine at stable doses at least 4 weeks prior to study entry must be willing to remain on the same stable dose during the study. In the unlikely event that a patient with PH2 is receiving pyridoxine, this should be discontinued at least 4 weeks prior to study entry
Exclusion Criteria
- •PH patients meeting any of the following criteria will be excluded from this study:
- •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 patient 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 acetaminophen daily.
- •6. History of alcohol consumption exceeding more than 21 units in males, 14 units in females, per week as determined by the Investigator. See Section 5 for details.
- •7. Women who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after last dosing of IMP.
- •8. Liver function test (LFT) abnormalities: ALT and/or AST >1.5 times ULN for age and gender.
- •9. 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
Investigators
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