Safety, Tolerability, and Pharmacodynamics of NOV-001 in Adult Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1-2a Safety, Tolerability, and Pharmacodynamics Controlled Study of NOV-001 in Healthy Volunteers and Patients With Enteric Hyperoxaluria

Conditions
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Healthy Volunteers, Enteric Hyperoxaluria

Intervention / Treatment
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* Combination Product: NOV-001
* Biological: NB1000S
* Drug: NB2000P
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Stage 1 placebo arm<br> | Drug: Placebo<br>* Placebo<br>|
| Experimental: Stage 1 NB1000S 10^9 CFU one time on Day 1<br> | Biological: NB1000S<br>* A recombinant live biotherapeutic product.<br>|
| Experimental: Stage 1 NB1000S 10^9 CFU one time on Day 1 and NB2000P 0.5g/day<br> | Combination Product: NOV-001<br>* NOV-001 is an investigational combination product composed of NB1000S, a recombinant live biotherapeutic product, and NB2000P, a botanically derived polysaccharide.<br>|
| Experimental: Stage 1 NB1000S 10^9 CFU one time on Day 1 and NB2000P 10g/day<br> | Combination Product: NOV-001<br>* NOV-001 is an investigational combination product composed of NB1000S, a recombinant live biotherapeutic product, and NB2000P, a botanically derived polysaccharide.<br>|
| Experimental: (Optional) Stage 1 variable doses of NB1000S and NB2000P at varying dosing regimens.<br>Adaptive trial design supports the enrollment of additional arms with variable doses of NB1000S, NB2000P, at varying frequencies of NB1000S and NB2000P administrations. | Combination Product: NOV-001<br>* NOV-001 is an investigational combination product composed of NB1000S, a recombinant live biotherapeutic product, and NB2000P, a botanically derived polysaccharide.<br>|
| Experimental: Stage 1 NB2000P at a dose to be determined<br> | Drug: NB2000P<br>* A botanically derived polysaccharide.<br>|
| Experimental: Stage 2 NOV-001 at dose determined in Stage 1<br>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. | Combination Product: NOV-001<br>* NOV-001 is an investigational combination product composed of NB1000S, a recombinant live biotherapeutic product, and NB2000P, a botanically derived polysaccharide.<br>|
| Placebo Comparator: Stage 2 placebo arm<br>In Stage 2, subjects will be randomized (3:1, NOV-001:placebo) to receive placebo for 28 days. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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