Safety, Tolerability and Pharmacokinetics of Oral NX-13 in Healthy Adults Male and Female Volunteers

NCT04458805 | Completed Phase 1 FDA Drug

• 1 other identifier: NX-13-1a
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, ascending dose, multi-cohort study. The study will be conducted in 2 parts: a single ascending dose (SAD) part (Part A) followed by a multiple ascending dose (MAD) part (Part B). The decision to escalate between dose levels and proceed to Part B will be based upon review of blinded available safety data by a Safety Review Committee.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (6)

• Specific assessments to evaluate the incidence, severity and relationship of adverse events (AEs)

  Specific assessments to evaluate treatment safety and tolerability include the following: the incidence, severity, and relationship of AEs

  Part A: 37 days Part B: 44 days

• Incidence of abnormal Physical examination findings

  Specific assessments to evaluate treatment safety and tolerability include the following: physical examinations

  Part A: 37 days Part B: 44 days

• Measurement of body weight (Part B only)

  Specific assessments to evaluate treatment safety and tolerability include the following: measurement of body weight (Part B only)

  Part A: 37 days Part B: 44 days

• Incidence of abnormal clinical laboratory test results

  Specific assessments to evaluate treatment safety and tolerability include the following: change from baseline in clinical laboratory parameters (ie, hematology, serum chemistry, coagulation, and urinalysis parameters)

  Part A: 37 days Part B: 44 days

• Incidence of abnormal ECG results

  Specific assessments to evaluate treatment safety and tolerability include the following: 12-lead ECG

  Part A: 37 days Part B: 44 days

• Incidence of abnormal vital signs

  Specific assessments to evaluate treatment safety and tolerability include the following: vital signs

  Part A: 37 days Part B: 44 days

Secondary Outcomes (4)

• Plasma concentration of NX-13

  Part A: 37 days Part B: 44 days

• Urine concentration of NX-13

  Part A: 37 days Part B: 44 days

• Fecal concentration of NX-13

  Part A: 37 days Part B: 44 days

• Measurement of NX-13 levels in stool

  Part A: 37 days Part B: 44 days

Study Arms (2)

NX-13 250mg

EXPERIMENTAL

Dose escalation in Part A will be conducted in 5 cohorts (Cohorts 1 to 5). Seven participants will be enrolled in each cohort and randomized to receive either NX-13 or placebo (ratio 5:2). NX-13 will be administered to Cohort 1 participants at the starting dose of 250 mg and increased in each new cohort. Five nominal dose levels in the range of 250 to 4000 mg have been selected for evaluation in Part A. The starting dose level in Part B will be determined by the SRC based on safety and tolerability data obtained in Part A. A dose level will only be evaluated in Part B if determined to be safe and tolerable in Part A. It is anticipated that 3 dose levels will be evaluated in Part B in a total of 3 cohorts (Cohorts 6 to 8). Seven participants will be enrolled in each cohort and will be randomized to receive a single oral dose of either NX-13 or placebo (ratio 5:2), once daily for seven days. NX-13 dose levels to be evaluated in Part B will be in the range of 500 to 4000 mg.

Drug: NX-13 250 mg

Placebo

PLACEBO COMPARATOR

Dose escalation in Part A will be conducted in 5 cohorts (Cohorts 1 to 5). Seven participants will be enrolled in each cohort and randomized to receive either NX-13 or placebo (ratio 5:2). NX-13 will be administered to Cohort 1 participants at the starting dose of 250 mg and increased in each new cohort. Five nominal dose levels in the range of 250 to 4000 mg have been selected for evaluation in Part A. The starting dose level in Part B will be determined by the SRC based on safety and tolerability data obtained in Part A. A dose level will only be evaluated in Part B if determined to be safe and tolerable in Part A. It is anticipated that 3 dose levels will be evaluated in Part B in a total of 3 cohorts (Cohorts 6 to 8). Seven participants will be enrolled in each cohort and will be randomized to receive a single oral dose of either NX-13 or placebo (ratio 5:2), once daily for seven days. NX-13 dose levels to be evaluated in Part B will be in the range of 500 to 4000 mg.

Drug: Placebo

Interventions

NX-13 250 mg DRUG

Dose escalation in Part A will be conducted in a total of 5 cohorts (Cohorts 1 to 5). Seven participants will be enrolled in each cohort and will be randomized to receive either NX-13 or placebo (ratio 5:2). NX-13 will be administered to Cohort 1 participants at the starting dose of 250 mg. The NX-13 dose will be increased in each new cohort. Five nominal dose levels in the range of 250 to 4000 mg have been selected for evaluation in Part A. It is anticipated that 3 dose levels will be evaluated in Part B in a total of 3 cohorts (Cohorts 6 to 8). Seven participants will be enrolled in each cohort and will be randomized to receive a single oral dose of either NX-13 or placebo (ratio 5:2), once daily for seven days.

NX-13 250mg

Placebo DRUG

Dose escalation in Part A will be conducted in a total of 5 cohorts (Cohorts 1 to 5). Seven participants will be enrolled in each cohort and will be randomized to receive either NX-13 or placebo (ratio 5:2). NX-13 will be administered to Cohort 1 participants at the starting dose of 250 mg. The NX-13 dose will be increased in each new cohort. Five nominal dose levels in the range of 250 to 4000 mg have been selected for evaluation in Part A. It is anticipated that 3 dose levels will be evaluated in Part B in a total of 3 cohorts (Cohorts 6 to 8). Seven participants will be enrolled in each cohort and will be randomized to receive a single oral dose of either NX-13 or placebo (ratio 5:2), once daily for seven days.

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers will be included in Part A or Part B of the study if they satisfy all the following criteria:
• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects;
• Adult males and females, 18 to 64 years of age (inclusive) at screening;
• Body mass index (BMI) ≥ 19.0 and ≤ 31.0 kg/m2, with a body weight ≥ 60.0 and ≤ 85.0 kg at screening;
• Be nonsmokers (including tobacco, e-cigarettes and marijuana) for at least 1 month prior to first study drug administration;
• Medically healthy without clinically significant abnormalities at screening and pre-dose on Day 1, including:
• Physical examination without any clinically relevant findings;
• Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes in supine position;
• Heart rate (HR) in the range of 50 to 100 bpm after 5 minutes rest in supine position;
• Body temperature, between 35.0°C and 37.5°C;
• No clinically significant findings in serum chemistry, hematology, coagulation and urinalysis tests as judged by the investigator;
• Conventional 12-lead ECG recording in triplicate (the mean of triplicate measurements will be used to determine eligibility at screening and Day-1) consistent with normal cardiac conduction and function, including:
• Normal sinus rhythm with HR between 50 and 100 bpm, inclusive;
• QTcF between 350 to 450 msec for male subjects and 350 to 470 msec for female subjects, inclusive;
• QRS duration of \< 120 msec;

You may not qualify if:

• Healthy volunteers will be excluded from Part A or Part B of the study if there is evidence of any of the following at screening, Day -1 or pre-dose on Day 1:
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the PI to be clinically relevant;
• Current infection that requires antibiotic, antifungal, antiparasitic or antiviral medications;
• Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma);
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia;
• Use of or plans to use systemic immunosuppressive (eg, corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (eg, interferon) during the study or within 4 months prior to the first study drug administration;
• Liver function test results (ie, AST, ALT, and gamma glutamyl transferase \[GGT\]) and total bilirubin must not be elevated more than 1.2-fold above the ULN;
• Positive test results for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies;
• History of active, latent or inadequately treated tuberculosis (TB) infection;
• Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs;
• Estimated creatinine clearance (CrCl) \< 40 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN;
• History of substance abuse or alcohol abuse within 12 months prior to first study drug administration;
• Positive drug or alcohol test results;
• Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, except occasional use of paracetamol;
• Demonstrated clinically significant (required intervention, eg, emergency room visit, epinephrine administration) allergic reactions (eg, food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the investigator, would interfere with the volunteer's ability to participate in the trial;

Sponsors & Collaborators

• Landos Biopharma Inc.: lead

Study Sites (1)

Nucleus Network

Melbourne, Australia

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

NX-13

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Simon Lichtiger, MD

  Landos Biopharma Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind, placebo-controlled, ascending dose, multi-cohort study. The study will be conducted in 2 parts: a single ascending dose (SAD) part (Part A) followed by a multiple ascending dose (MAD) part (Part B). The decision to escalate between dose levels and proceed to Part B will be based upon review of blinded available safety data by a Safety Review Committee. Part A: 35 healthy volunteers will be enrolled in a total of 5 cohorts. Each cohort will enroll 7 participants with 5 participants randomized to receive NX-13 and 2 participants randomized to receive placebo. Part B: 21 healthy volunteers will be enrolled in a total of 3 cohorts. Each cohort will enroll 7 participants with 5 participants randomized to receive NX-13 and 2 participants randomized to receive placebo.

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: July 7, 2020
• Study Start: July 10, 2020
• Primary Completion: October 21, 2020
• Study Completion: October 21, 2020
• Last Updated: March 10, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)