Enteric Hyperoxaluria, Healthy Volunteers
Conditions
Keywords
Healthy volunteers, Safety, Tolerability, Enteric hyperoxaluria, Kidney stone, Roux-en-Y gastric bypass, Hyperoxaluria, Secondary hyperoxaluria, Oxalate, Kidney calcification, Gastric bypass, Biliopancreatic diversion with duodenal switch, Duodenal switch
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.
Interventions
COMBINATION_PRODUCTNOV-001
NOV-001 is an investigational combination product composed of NB1000S, a recombinant live biotherapeutic product, and NB2000P, a botanically derived polysaccharide.
BIOLOGICALNB1000S
A recombinant live biotherapeutic product.
DRUGNB2000P
A botanically derived polysaccharide.
DRUGPlacebo
Placebo
Sponsors
Novome Biotechnologies Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Stage 1 Key Inclusion Criteria: * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | Up to 182 days |
Other
| Measure | Time frame |
|---|---|
| Proportion of patients achieving ≥ 20% reduction in 24-hour UOx excretion from baseline to end of treatment, NOV-001 compared to placebo. | Stage 2; 28 days |
| NB1000S engraftment as measured by quantitative Polymerase Chain Reaction (qPCR) determination of concentration of NB1000S strain genomic copies (cells/mL) in stool, change from baseline. | Up to 182 days |
| The proportion of subjects with NB100S strain abundance in stool, as measured by qPCR determination of concentration of strain genomic copies (cells/mL). | Up to 182 days |
| Percent change from baseline in 24-hour UOx excretion (mg/mL), NOV-001 compared to placebo. | Stage 2; 28 days |
| Fecal shedding of NB1000S strain as measured by qPCR determination of concentration of NB1000S strain genomic copies (cells/mL), during treatment and follow-up periods. | Up to 182 days |
| Absolute change from baseline in 24-hour urinary oxalate (UOx) excretion (mg/mL), NOV-001 compared to placebo. | Stage 2; 28 days |
| Time to strain engraftment, based on the time to reach NB1000S strain abundance by qPCR determination of concentration of NB1000S strain genomic copies (cells/mL). | Up to 182 days |
Countries
Canada, United States
Outcome results
None listed