Safety, Tolerability, and Pharmacodynamics of NOV-001 in Adult Subjects
- Conditions
- Healthy VolunteersEnteric Hyperoxaluria
- Interventions
- Registration Number
- NCT04909723
- Lead Sponsor
- Novome Biotechnologies Inc
- Brief Summary
The first stage of this study is a prospective, adaptive, Phase 1, first-in-human, randomized, controlled study evaluating safety, tolerability, and pharmacodynamics of NOV-001 in adult healthy volunteers.
The second stage of this study is a prospective, randomized, single-blinded, placebo-controlled study of safety, tolerability, and early efficacy in patients with enteric hyperoxaluria.
- Detailed Description
This study is evaluating the safety, tolerability, pharmacodynamics, and early efficacy of NOV-001. NOV-001 is an investigational combination product composed of NB1000S, a recombinant live biotherapeutic product, and NB2000P, a botanically derived polysaccharide. In Stage 1, NB1000S (or placebo) is administered on the first day of treatment and NB2000P is administered once daily, or as indicated in the adaptive study design. In Stage 2, NB1000S (or placebo) is administered two times per day on the first day of the treatment and NB2000P (or placebo) is administered once daily for 28 days, at doses determined in Stage 1.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 153
- Ages 18 to 55
- Body mass index (BMI) < 38 kg/m2.
- Healthy as defined by no clinically relevant abnormalities being identified by a detailed medical history, physical examination, and clinical laboratory tests.
- If woman of child-bearing potential, must not be pregnant, and must also agree to use an appropriate highly-effective contraceptive.
- Willing and able to comply with all study requirements, including duration of stay at inpatient unit, dietary restrictions, daily study product administration, pregnancy testing and contraception (if applicable), stool collections, and blood and urine collections.
Stage 1 Key
- Estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2 at Screening.
- Oral or parenteral antibiotics within 4 weeks prior to Screening, or anticipation of the need for such antibiotics during the Screening or treatment periods of the study.
- Current or history of any clinically significant medical illness or disorder the Investigator considers should exclude the subject from the study.
- Participation in any investigational intervention study within 30 days prior to study product administration in this study.
- Known hypersensitivity to omeprazole.
- Applicable only to certain study groups depending on emerging Stage 1 data: no current or anticipated use during the screening or treatment periods of the study of medications that have the potential for drug-drug interactions (DDI) with omeprazole.
Stage 2 Key Inclusion Criteria:
- Ages 18 to 65.
- Hyperoxaluria secondary to Roux-en-Y gastric bypass surgery or to biliopancreatic diversion with duodenal switch (BPD-DS) surgery.
- 24-Hour urinary oxalate (UOx) ≥ 60 mg.
- If woman of child-bearing potential, must not be pregnant and must also agree to use an appropriate highly effective contraceptive method.
- Must, in the opinion of the Investigator, be in otherwise good health.
- Willing and able to comply with all study requirements, including dietary restrictions, daily study product administration, pregnancy testing and contraception (if applicable), stool collections, and blood and 24-hour urine collections.
Stage 2 Key Exclusion Criteria:
- Chronic kidney disease with eGFR < 30 mL/min/1.73 m2 at Screening.
- Evidence of current acute renal injury or ongoing clinically significant renal disease.
- Oral or parenteral antibiotics within 4 weeks prior to Screening, or anticipation of the need for such antibiotics during the Screening or treatment periods of the study (topical antibiotics are permissible.)
- Taking during the study any treatment for hyperoxaluria except for NOV-001, other than stable treatments for the management of kidney stones.
- Taking Vitamin C ≥ 300 mg/day for > 10 days within 7 days prior to Screening; unwilling or unable to discontinue and/or avoid Vitamin C supplementation for the duration of study product treatment.
- Known active autoimmune disorder or other condition requiring high dose of systemic corticosteroids (i.e., > 10 mg/day prednisone or equivalent) or other immunosuppressant therapy.
- Current or history of any clinically significant medical illness or disorder other than enteric hyperoxaluria that the Investigator considers should exclude the patient from the study.
- Participation in any investigational intervention study within 30 days prior to study product administration in this study.
- Known hypersensitivity to omeprazole.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stage 2 NOV-001 at dose determined in Stage 1 NOV-001 In Stage 2, subjects will be randomized (3:1, NOV-001:placebo) to receive NOV-001 (consisting of NB1000S and NB2000P at a dose and regimen determined in Stage 1) for 28 days. Stage 2 placebo arm Placebo In Stage 2, subjects will be randomized (3:1, NOV-001:placebo) to receive placebo for 28 days. Stage 1 NB1000S 10^9 CFU one time on Day 1 and NB2000P 0.5g/day NOV-001 - Stage 1 placebo arm Placebo - Stage 1 NB1000S 10^9 CFU one time on Day 1 NB1000S - Stage 1 NB1000S 10^9 CFU one time on Day 1 and NB2000P 10g/day NOV-001 - (Optional) Stage 1 variable doses of NB1000S and NB2000P at varying dosing regimens. NOV-001 Adaptive trial design supports the enrollment of additional arms with variable doses of NB1000S, NB2000P, at varying frequencies of NB1000S and NB2000P administrations. Stage 1 NB2000P at a dose to be determined NB2000P -
- Primary Outcome Measures
Name Time Method Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Up to 182 days
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (19)
Indiana University
🇺🇸Carmel, Indiana, United States
Clinical Research Solutions
🇺🇸Cleveland, Ohio, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Prohealth Research Center
🇺🇸Doral, Florida, United States
Chesapeake Urology Associates
🇺🇸Hanover, Maryland, United States
Florida Urology Partners
🇺🇸Tampa, Florida, United States
The Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Advanced Urology Institute
🇺🇸Daytona Beach, Florida, United States
Idaho Urologic Institute
🇺🇸Meridian, Idaho, United States
Georgia Clinical Research
🇺🇸Lawrenceville, Georgia, United States
Washington University, St. Louis
🇺🇸Saint Louis, Missouri, United States
Associated Urologists of North Carolina
🇺🇸Raleigh, North Carolina, United States
AMR Knoxville
🇺🇸Knoxville, Tennessee, United States
Knoxville Kidney Center
🇺🇸Knoxville, Tennessee, United States
Houston Metro Urology
🇺🇸Houston, Texas, United States
Alpha Recherche Clinique
🇨🇦Quebec City, Quebec, Canada