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

Sponsor

Novome Biotechnologies Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04909723

Collaborator

(none)

115

Enrollment

Locations

Arms

Anticipated Duration (Months)

6.8

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers Enteric Hyperoxaluria	Combination Product: NOV-001 Biological: NB1000S Drug: NB2000P Drug: Placebo	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

115 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 2, 2021

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
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]
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]
Percent change from baseline in 24-hour UOx excretion (mg/mL), NOV-001 compared to placebo. [Stage 2; 28 days]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35205
2	National Institute of Clinical Research	Garden Grove	California	United States	92844
3	Advanced Urology Institute	Daytona Beach	Florida	United States	32114
4	Prohealth Research Center	Doral	Florida	United States	33166
5	Florida Urology Partners	Tampa	Florida	United States	33615
6	Georgia Clinical Research	Lawrenceville	Georgia	United States	30044
7	Indiana University	Carmel	Indiana	United States	46032
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	Washington University, St. Louis	Saint Louis	Missouri	United States	63130
10	Associated Urologists of North Carolina	Raleigh	North Carolina	United States	27612
11	University of Cincinnati	Cincinnati	Ohio	United States	45221
12	Clinical Research Solutions	Middleburg Heights	Ohio	United States	44130
13	The Miriam Hospital	Providence	Rhode Island	United States	02906
14	AMR Knoxville	Knoxville	Tennessee	United States	37920
15	Knoxville Kidney Center	Knoxville	Tennessee	United States	37923
16	Houston Metro Urology	Houston	Texas	United States	77027
17	Alpha Recherche Clinique	Québec City	Quebec	Canada	QC G2J 0C4