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

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

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.

Study Overview

• Status: Terminated
• Conditions: Healthy Volunteers; Enteric Hyperoxaluria
• Intervention / Treatment: Drug: Placebo; Biological: NB1000S; Combination product: NOV-001; Drug: NB2000P

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 Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lachy McLean, MB ChB, PhD; Phone Number: 415-894-0999; Email: lmclean@novomebio.com
• Study Contact Backup: Name: Polina Bukshpun; Email: pbukshpun@novomebio.com

Study Locations

• Canada
  • Quebec
    • Quebec City, Quebec, Canada, QC G2J 0C4
      • Alpha Recherche Clinique
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Advanced Urology Institute
    • Doral, Florida, United States, 33166
      • Prohealth Research Center
    • Tampa, Florida, United States, 33615
      • Florida Urology Partners
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • Georgia Clinical Research
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Maryland
    • Hanover, Maryland, United States, 21076
      • Chesapeake Urology Associates
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University, St. Louis
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Associated Urologists of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44130
      • Clinical Research Solutions
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center
    • Knoxville, Tennessee, United States, 37290
      • AMR Knoxville
  • Texas
    • Houston, Texas, United States, 77027
      • Houston Metro Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

8

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Novome Biotechnologies Inc
• Investigators: Study Director: Lachy McLean, MB ChB, PhD, Novome Biotechnologies Inc

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): April 6, 2023

Study Registration Dates

• First Submitted: May 7, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Healthy volunteers; Safety; Tolerability; Roux-en-Y gastric bypass; Gastric bypass; Biliopancreatic diversion with duodenal switch; Oxalate; Hyperoxaluria; Kidney stone; Enteric hyperoxaluria; Secondary hyperoxaluria; Kidney calcification; Duodenal switch
• Other Study ID Numbers: NOV-001-CL01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No