Safety, Tolerability, and Pharmacokinetics of Oral BT-11 in Healthy Adult Male and Female Volunteers

A Randomized, Placebo-Controlled, Sequential Single and Multiple Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral BT-11 in Healthy Adult Male and Female Volunteers

Study type: Interventional Description of intervention(s) / exposure

For single ascending dose, five dose target ranges of BT-11 (depending on body weight the doses in each cohort will be 5.9 - 7.7 mg/kg; 18.9 - 25.0 mg/kg; 44.3 - 50.0 mg/kg; 68.5 - 75 mg/kg and 94.2 - 100.0 mg/kg) will be evaluated, based on subject's weight on Day 1.

For multiple ascending dose (once daily for 7 days), three dose target ranges of BT-11 (depending on body weight the doses in each cohort will be 5.9 - 7.7 mg/kg; 44.3 - 50.0 mg/kg; and 94.2 - 100.0 mg/kg) will be evaluated, based on subject's weight on Day 1.

White tablets containing 500 mg BT-11 or matching placebo tablets will be dispensed.

Single ascending dose duration of administration will be once. For multiple ascending dose it will be up to 7 days.

The mode administration will be oral tablet. Compliance and adherence to the intervention will be performed based on the tablet return, tablet not consumed by the subject.

The safety monitoring committee will evaluate safety at conclusion of single ascending cohort 2 prior to the commencement of dosing for the multiple ascending dose.

Study Overview

• Status: Completed
• Conditions: Normal Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: BT-11

Detailed Description

Primary outcome: To assess the safety and tolerability of BT-11 after single and multiple ascending oral dose administration in healthy volunteers

The safety and tolerability profile of BT-11 as evidenced by the occurrence, timing, frequency, and severity of adverse events (AE) and clinically significant:

• laboratory abnormalities Haematology, Coagulation, Serum Chemistry, Urinalysis, HIV, HBsAg, HCV
• physical exam findings Complete physical exam include, at a minimum, assessment of the following systems: skin, head, ears, eyes, nose and throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system
• 12-lead ECG aberrations ECG data (RR, PR, QRS, QT and QTcF intervals and pulse rate)
• and/or vital signs abnormalities Vital signs assessments will include systolic and diastolic blood pressure, pulse, tympanic body temperature, and respirations

Timepoint: Adverse events will be recorded from the time of first dosing through to end of study date.

Laboratory abnormalities at the screening visit, up to 28 days prior to the first dose of study medication then up to end of study visit.

Physical Exam findings will be collected at screening, Day-1 and Day 2 for the single ascending dose. For multiple ascending dose it will be collected at screening, Day-1, Day 3, Day 5 and Day 7

12-lead ECG aberrations will be collected from Screening then on Day -1 and Day 2 for the single ascending dose. For MAD it will be collected at screening, Day-1, Day 3, Day 5 and Day 7

Vital signs abnormalities collected from Screening then on Day -1 and Day 2 for the single ascending dose. For MAD it will be collected at screening, Day-1, Day 3, Day 5 and Day 7

Primary outcome: To assess the safety and tolerability of BT-11 after single and multiple ascending oral dose administration in healthy volunteers.

Timepoint: For single ascending dose blood samples for PK analysis will be collected pre-dose and at 15, 30, 45 minutes, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

Urine samples for PK analysis will be collected pre-dose and 0-24 hours post-dose;

For multiple ascending blood samples for PK analysis will be collected pre-dose and at 15, 30, and 45 min and 1, 1.25 1.5, 2, 3, 4, 6, 8, 10, 12 and 18 hours post Day 1 dose. Pre-dose on Day 2

Urine samples for PK analysis will be collected on Day 1, pre-dose and at 0-24 hours post-dose

On follow up period, Day 3 to Day 6, Plasma samples for PK analysis will be collected pre-dose on each day.

Secondary outcome: The following PK parameters will be determined:

• Time to maximum concentration (tmax);
• Maximum concentration (Cmax);
• Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-tlast);
• Area under the concentration-time curve from time 0 to infinity (AUC0-inf);
• Terminal Elimination Rate Constant (kel);
• Terminal half-life (t1/2);
• Terminal clearance (CL/F);
• Volume of distribution (Vd/F).

Timepoint: The following PK parameters will be determined for single ascending dose:

Area under the concentration-time curve from time 0 to 24 hours from start of first dose (AUC0-24h);

• Amount of drug excreted in urine in each collection interval

For the multiple ascending dose:

Area under the concentration-time curve from time 0 to 24 hours from start dosing (AUC0-24h) on Day 1 and 0 to 24 hours (AUC0-24h) following the last dose on Day 7;

• Pre-dose trough on Days 2, 3, 4, 5 and 6;
• Amount of drug excreted in urine in each collection interval;
• Volume of distribution at steady state (Vss/F).

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Site

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Healthy male and female volunteers aged 18 to 65 years, inclusive.
2. Body weight 65 - 85 kg.
3. Volunteer has read, confirmed understanding of, and signed the written informed consent form after the nature of the study and all essential elements of the informed consent document have been fully explained and all of the Volunteer's questions have been answered to his or her satisfaction, prior to initiation of any study procedures.

Key Exclusion Criteria:

1. Any clinically significant abnormality identified in the screening history, physical examination (including Vital Signs), laboratory testing, or electrocardiographic testing. Repeat testing of vital signs to confirm the value is allowed. Up to two repeat tests are permitted to confirm eligibility.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral tablet
Experimental: BT-11	Drug: BT-11; Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability	up to 14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
PK	24 hours

Collaborators and Investigators

• Sponsor: NImmune Biopharma
• Investigators: Study Director: Simon Lichtiger, MD, Landos Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2018
• Primary Completion (Actual): September 24, 2018
• Study Completion (Actual): December 13, 2018

Study Registration Dates

• First Submitted: February 3, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: BT-11-1a

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
• product manufactured in and exported from the U.S.: No