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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04909723
• Other study ID #: NOV-001-CL01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 2, 2021
• Est. completion date: April 6, 2023

Study information

• Verified date: May 2023
• Source: Novome Biotechnologies Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 153
• Est. completion date: April 6, 2023
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Enteric Hyperoxaluria
• Healthy Volunteers

Intervention

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.

Biological:
• NB1000S
A recombinant live biotherapeutic product.

Drug:
• NB2000P
A botanically derived polysaccharide.
• Placebo
Placebo

Locations

Country	Name	City	State
Canada	Alpha Recherche Clinique	Quebec City	Quebec
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Indiana University	Carmel	Indiana
United States	University of Cincinnati	Cincinnati	Ohio
United States	Clinical Research Solutions	Cleveland	Ohio
United States	Advanced Urology Institute	Daytona Beach	Florida
United States	Prohealth Research Center	Doral	Florida
United States	Chesapeake Urology Associates	Hanover	Maryland
United States	Houston Metro Urology	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	AMR Knoxville	Knoxville	Tennessee
United States	Knoxville Kidney Center	Knoxville	Tennessee
United States	Georgia Clinical Research	Lawrenceville	Georgia
United States	Idaho Urologic Institute	Meridian	Idaho
United States	The Miriam Hospital	Providence	Rhode Island
United States	Associated Urologists of North Carolina	Raleigh	North Carolina
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University, St. Louis	Saint Louis	Missouri
United States	Mayo Clinic	Scottsdale	Arizona
United States	Florida Urology Partners	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novome Biotechnologies Inc

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	Absolute change from baseline in 24-hour urinary oxalate (UOx) excretion (mg/mL), NOV-001 compared to placebo.		Stage 2; 28 days
Other	Percent change from baseline in 24-hour UOx excretion (mg/mL), NOV-001 compared to placebo.		Stage 2; 28 days
Other	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
Primary	Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0		Up to 182 days