Safety and Pharmacokinetic Study of LMN-101 in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This will be a randomized, double-blind, placebo-controlled, dose-escalation study of 3 dose levels of LMN-101. Healthy volunteers will take LMN-101 or placebo orally either as a single dose or at one of three dose levels three times daily over 28 days. Protocol-specified evaluations and procedures will be performed on Days 1-2 and every one-two weeks during dosing. Study observation will continue until 4 weeks after the last dose of study drug.

Detailed Description
-----------------
Healthy volunteers will be sequentially assigned to the following dosing regimens: Part A: A single, open-label dose of 3000 mg orally (2 subjects) Part B: Subjects will be randomized within a dose regimen to active or placebo treatment: 300 mg PO TID (three times daily) given as a single 300-mg capsule of LMN-101 orally three times daily for 28 days (4 subjects) or identical-appearing placebo capsule (2 subjects). 1000 mg PO TID given as two 500-mg capsules of LMN-101 orally three times daily for 28 days (4 subjects) or identical-appearing placebo capsules (2 subjects). 3000 mg PO TID given as six 500-mg capsules of LMN-101 orally three times daily for 28 days (4 subjects) or identical-appearing placebo capsules (2 subjects). The primary endpoint is: • Safety and tolerability of LMN-101. The secondary endpoints are: Peak serum drug concentration following administration of the initial dose and peak serum drug concentration following a course of treatment (if systemic absorption is observed). Area under the serum drug concentration versus time curve (AUC) following administration of the initial dose and following a course of treatment (if systemic absorption is observed). Induction of serum anti-drug antibodies (if systemic absorption is observed).

Official Title
-----------------
A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Safety and Pharmacokinetic Study of LMN-101 in Healthy Volunteers

Conditions
-----------------
Campylobacter Jejuni Infection

Intervention / Treatment
-----------------
* Biological: LMN-101


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female between 18 and 50 years, inclusive, at time of informed consent Willingness to participate after written informed consent obtained Available for all planned clinical visits for physical examinations, blood draws, stool collections General good health, without significant medical illness or abnormal physical examination findings as determined by the PI. Adequate bone marrow reserve, renal and liver function. Absolute neutrophil count ≥ 1.5 x 10e9/L Lymphocyte count < 6.0 x 10e9/L Platelet count ≥ 150 x 10e9/L Hemoglobin ≥ 110 g/L Estimated glomerular filtration rate ≥ 40 mL/min/1.73 meter squared Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN) Total bilirubin ≤ 1.5x ULN Serum albumin ≥ 28 g/L Females of childbearing potential should be using and committed to continue using one of the following acceptable birth control methods: Sexual abstinence (inactivity) or exclusively same-sex partner for 1 month prior to screening through study completion; or Intrauterine device (IUD) in place for at least 1 month prior to study through study completion; or Stable hormonal contraception for at least 1 month prior to study through study completion; or Surgical sterilization (vasectomy) of male partner at least 6 months prior to study. To be considered of non-childbearing potential, females should be surgically sterilized (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 2 months prior to study) or be post-menopausal and at least 3 years since last menses. Male participants must use condoms during the study and through study completion. Exclusion Criteria: Treatment with an experimental compound within 30 days. Treatment within 30 days or planned use within the study period with immunomodulator or immunosuppressant agent. Pregnancy or breastfeeding. Presence of any of the following clinical conditions: History of one or more of the following: cardiac insufficiency (NYHA III/IV), uncontrolled cardiac arrhythmias, unstable ischemic heart disease, or uncontrolled hypertension (systolic blood pressure > 170 mmHg or diastolic blood pressure > 110 mmHg). History of venous thromboembolic disease within 12 months, myocardial infarction, or cerebrovascular accident. Unstable pulmonary, renal, hepatic, endocrine or hematologic disease. Gastrointestinal disorder requiring ongoing care by a physician. Autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to rheumatoid arthritis. Evidence of active malignant disease, malignancies diagnosed within the previous 5 years, or breast cancer diagnosed within the previous 5 years (except skin cancers other than melanoma). Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections; or major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks. Positive serology for human immunodeficiency virus (HIV) infection or history of other immunodeficiency illness. Positive serology results for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) Significant neuromuscular disease or neuropathy Psychiatric condition Alcohol or illicit drug abuse/dependency or positive urine toxicology screen for drugs of abuse other than marijuana. Alcohol and tobacco consumption are permitted.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part A: Open Label Part B: Randomized, Double-Blind, Placebo-Controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part B: Cohort 1<br>300 mg PO TID given as a single 300-mg capsule of LMN-101 orally three times daily for 28 days | Biological: LMN-101<br>* variable heavy chain-derived binding protein designed to bind and inhibit flagellin filament protein of Campylobacter jejuni, delivered in whole spray-dried, encapsulated spirulina biomass<br>|
| Active Comparator: Part B: Cohort 2<br>1000 mg PO TID given as two 500-mg capsules of LMN-101 orally three times daily for 28 days | Biological: LMN-101<br>* variable heavy chain-derived binding protein designed to bind and inhibit flagellin filament protein of Campylobacter jejuni, delivered in whole spray-dried, encapsulated spirulina biomass<br>|
| Active Comparator: Part B: Cohort 3<br>3000 mg PO TID given as six 500-mg capsules of LMN-101 orally three times daily for 28 days | Biological: LMN-101<br>* variable heavy chain-derived binding protein designed to bind and inhibit flagellin filament protein of Campylobacter jejuni, delivered in whole spray-dried, encapsulated spirulina biomass<br>|
| Other: Part A<br>3000 mg PO single dose given as six 500-mg capsules of LMN-101 orally | Biological: LMN-101<br>* variable heavy chain-derived binding protein designed to bind and inhibit flagellin filament protein of Campylobacter jejuni, delivered in whole spray-dried, encapsulated spirulina biomass<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of adverse events in LMN-101 subjects compared to placebo subjects | adverse events graded according to severity and rates compared between LMN-101 subjects and placebo subjects | Day 1 to Day 56 | 
| Tolerability of LMN-101: proportion of subjects completing study drug compared to placebo | proportion of subjects completing study drug and remaining on study and free from possibly drug-related and dose-limiting serious adverse events | Day 1 to Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Peak serum concentration in LMN -101 subjects | Peak serum drug concentration in subjects receiving LMN-101 | Day 1 to Day 29 | 
| Pharmacokinetics: area under the curve in serum | Area under the serum drug concentration versus time curve in subjects receiving LMN-101 at each dose level | Day 1 to Day 29 | 
| Anti-Drug Antibodies | Induction of serum anti-drug IgG antibodies | Day 1 to Day 56 |