Clinical trial NCT04862741: Safety, Tolerability, and Pharmacokinetics of Oral NX-13 in Active Ulcerative Colitis
Official title: A Randomized, Double-blind Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral NX-13 in Active Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Lead sponsor: Landos Biopharma Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-28
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b, randomized, double-blind, multicenter dose-ranging study to evaluate the safety, tolerability, and PK of NX-13. Approximately 40 subjects will be randomized in a 3:3:3:1 ratio to receive 1 of 3 NX-13 treatment regimens (NX-13 250 mg IR, 500 mg IR, 500 mg MR) (12 evaluable subjects at each of the 3 dose levels) or placebo (4 subjects), once daily for 28 consecutive days.

Detailed description: Following screening period (up to 28 days in length), a total of 40 subjects are planned to be enrolled into this study from multiple sites in the United States, Australia, New Zealand, and Moldova. Eligible subjects will be randomized in a 3:3:3:1 ratio to receive 1 of 3 NX-13 treatment regimens (NX-13 250 mg IR, 500 mg IR, 500 mg MR) or placebo via a computer-generated interactive web response system (IWRS). Each of the NX-13 treatment groups will comprise 12 subjects and 4 subjects will be randomized to receive placebo. The study will include a maximum of 25% of subjects who have had prior exposure to biologic therapy for UC.

Dosing will extend over a 28-day period at each dose level. Subjects will receive the first dose of study drug in clinic on Day 1 (Visit 2) and Day 28 (Visit 4/EOT) but will self-administer IP at home once daily for the remaining dosing days. The study duration will be approximately 63 days: Screening Period (28 days) + Treatment Period (28 days) + Safety Follow-up (7 days after last dose). There will be a follow-up visit on Day 35 (Visit 5).

Eligibility criteria: Key Inclusion Criteria:

* male and female subjects aged 18 to 75 years (inclusive) with a diagnosis of UC ≥ 90 days before screening;
* active UC defined as a total Mayo Score of 4 to 10 (inclusive), at baseline, with a Mayo endoscopic subscore (MES) ≥ 2 confirmed by a central reader;
* baseline fecal calprotectin ≥ 250 μg/g;
* biologic-naïve or having stopped biologic therapy ≥ 8 weeks before the start of the study;
* 5-aminosalicylates must be stable for ≥ 1 month prior to randomization.

Key Exclusion Criteria:

* Crohn's disease (CD), indeterminate colitis, or presence or history of fistula with CD;
* a history of toxic megacolon, abdominal abscess, symptomatic colonic stricture, or stoma;
* history of or at imminent risk of colectomy;
* history of or current colonic dysplasia ;
* recent history (within 2 years prior to randomization) or current adenomatous colonic polyps;
* treatment with an immunosuppressant within 3 months of randomization;
* bacterial or parasitic pathogenic enteric infection;
* live virus vaccination within 1 month prior to screening.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events after multiple oral dose administration of NX-13 in subjects with active ulcerative colitis (UC)
timeFrame: 63 days
Secondary outcomes:
measure: PK profile of NX-13 after multiple oral dose administration in subjects with active UC
timeFrame: 63 days
measure: PK Parameters - Time to maximum concentration (tmax);
timeFrame: 63 days
measure: PK Parameters- Maximum concentration (Cmax)
timeFrame: 63 days
measure: PK Parameters- Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-tlast);
timeFrame: 63 days
measure: PK Parameters-Terminal half-life (t1/2)
timeFrame: 63 days
measure: PK Parameters- clearance (CL);
timeFrame: 63 days
measure: PK Parameters- Vz, apparent volume of distribution during terminal phase.
timeFrame: 63 days
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Avant Research Associates LLC
state: Alabama
city: Lancaster
country: United States
facility: Om Research LLC
state: California
city: Mission Viejo
country: United States
facility: Allameh Medical Corporation
state: California
city: Northridge
country: United States
facility: California Medical Research Associates, Inc.
state: California
city: Walnut Creek
country: United States
facility: Clinical Research of California
state: California
city: Kissimmee
country: United States
facility: I.H.S Health LLC
state: Florida
city: Miami
country: United States
facility: University of Miami Crohn's and Colitis Center
state: Florida
city: Miami
country: United States
facility: Valencia Medical and Research Center
state: Florida
city: Orlando
country: United States
facility: Care Access
state: Florida
city: Pensacola
country: United States
facility: Gastroenterology Associates of Pensacola, P.A.
state: Florida
city: Decatur
country: United States
facility: Atlanta Center for Gastroenterology, P.C.
state: Georgia
city: New York
country: United States
facility: Care Access
state: New York
city: Lumberton
country: United States
facility: Care Access
state: North Carolina
city: Columbus
country: United States
facility: Optimed Research, LTD
state: Ohio
city: Pottsville
country: United States
facility: Care Access
state: Pennsylvania
city: Chattanooga
country: United States
facility: Galen Medical Group
state: Tennessee
city: Austin
country: United States
facility: Avant Research Associates, LLC
state: Texas
city: Houston
country: United States
facility: Biopharma Informatics, LLC
state: Texas
city: Pearland
country: United States
facility: LinQ Research, LLC
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute, LLC
state: Texas
city: Victoria
country: United States
facility: Victoria Gastroenterology
state: Texas
city: Salt Lake City
country: United States
facility: Care Access Research, Salt Lake City
state: Utah
city: Dnipro
country: Ukraine
facility: Communal Enterprise I.I.Mechnykov Dnipropetrovsk Regional Clinical Hospital of Dnipropetrovsk Regional Counsil, cont.
city: Ivano-Frankivs'k
country: Ukraine
facility: Communal Non-commercial Enterprise Regional Clinical Hospital of Ivano-Frankivsk Regional Council
city: Kyiv
country: Ukraine
facility: Medical Center 'Ok!Clinic+' of Copmany with limited liability "International institue of Clinical Research"
city: Kyiv
country: Ukraine
facility: Clinical Hospital "Feofaniya" of State Management of Affairs, Center of Gastroenterology and Endocrinology
city: Kyiv
country: Ukraine
facility: Communal Non-commercial Enterprise of Kyiv Regional Council Kyiv Regional Hospital, Department of Therapy
city: Vinnytsia
country: Ukraine
facility: Communal Non-Commercial Enterprise of M.I. Pyrohov Vinnytsia Regional Clinical Hospital of Vinnytsia Regional Council
city: Vinnytsia
country: Ukraine
facility: Communal Non-commercial Enterprise Vinnytsia City Clinical Hospital #1, Department of Gastroenterology
city: Zaporizhzhya
country: Ukraine
facility: Medical Center of Limited Liability Company Gastroenterology Center IBD TEAM
city: Zhytomyr
country: Ukraine
facility: Communal Non-commercial Enterprise O.F. Herbachevskyi Regional Clinical Hospital of Zhytomyr Regional Council
Study officials:
affiliation: Landos Biopharma Inc.
name: Simon Lichtiger, MD
role: STUDY_DIRECTOR
References: