Clinical trial NCT04909723: Safety, Tolerability, and Pharmacodynamics of NOV-001 in Adult Subjects
Official title: Phase 1-2a Safety, Tolerability, and Pharmacodynamics Controlled Study of NOV-001 in Healthy Volunteers and Patients With Enteric Hyperoxaluria
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Healthy Volunteers
Enteric Hyperoxaluria
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
Lead sponsor: Novome Biotechnologies Inc
Sponsor class: INDUSTRY
First posted: 2021-06-02
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
timeFrame: Up to 182 days
Secondary outcomes:
Other outcomes:
measure: 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.
timeFrame: Up to 182 days
measure: The proportion of subjects with NB100S strain abundance in stool, as measured by qPCR determination of concentration of strain genomic copies (cells/mL).
timeFrame: Up to 182 days
measure: 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).
timeFrame: Up to 182 days
measure: 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.
timeFrame: Up to 182 days
measure: Absolute change from baseline in 24-hour urinary oxalate (UOx) excretion (mg/mL), NOV-001 compared to placebo.
timeFrame: Stage 2; 28 days
measure: Percent change from baseline in 24-hour UOx excretion (mg/mL), NOV-001 compared to placebo.
timeFrame: Stage 2; 28 days
measure: Proportion of patients achieving ≥ 20% reduction in 24-hour UOx excretion from baseline to end of treatment, NOV-001 compared to placebo.
timeFrame: Stage 2; 28 days
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Daytona Beach
country: United States
facility: Advanced Urology Institute
state: Florida
city: Doral
country: United States
facility: Prohealth Research Center
state: Florida
city: Tampa
country: United States
facility: Florida Urology Partners
state: Florida
city: Lawrenceville
country: United States
facility: Georgia Clinical Research
state: Georgia
city: Meridian
country: United States
facility: Idaho Urologic Institute
state: Idaho
city: Carmel
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Hanover
country: United States
facility: Chesapeake Urology Associates
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Raleigh
country: United States
facility: Associated Urologists of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Clinical Research Solutions
state: Ohio
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Knoxville
country: United States
facility: AMR Knoxville
state: Tennessee
city: Knoxville
country: United States
facility: Knoxville Kidney Center
state: Tennessee
city: Houston
country: United States
facility: Houston Metro Urology
state: Texas
city: Quebec City
country: Canada
facility: Alpha Recherche Clinique
state: Quebec
Study officials:
affiliation: Novome Biotechnologies Inc
name: Lachy McLean, MB ChB, PhD
role: STUDY_DIRECTOR
References: