Safety and Pharmacokinetic Study of LMN-101 in Healthy Volunteers

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

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.

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).

Inclusion Criteria:

1. Male or female between 18 and 50 years, inclusive, at time of informed consent

2. Willingness to participate after written informed consent obtained

3. Available for all planned clinical visits for physical examinations, blood draws, stool collections

4. General good health, without significant medical illness or abnormal physical examination findings as determined by the PI.

5. Adequate bone marrow reserve, renal and liver function.

   1. Absolute neutrophil count ≥ 1.5 x 10e9/L
   2. Lymphocyte count < 6.0 x 10e9/L
   3. Platelet count ≥ 150 x 10e9/L
   4. Hemoglobin ≥ 110 g/L
   5. Estimated glomerular filtration rate ≥ 40 mL/min/1.73 meter squared
   6. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN)
   7. Total bilirubin ≤ 1.5x ULN
   8. Serum albumin ≥ 28 g/L

6. Females of childbearing potential should be using and committed to continue using one of the following acceptable birth control methods:

   1. Sexual abstinence (inactivity) or exclusively same-sex partner for 1 month prior to screening through study completion; or
   2. Intrauterine device (IUD) in place for at least 1 month prior to study through study completion; or
   3. Stable hormonal contraception for at least 1 month prior to study through study completion; or
   4. Surgical sterilization (vasectomy) of male partner at least 6 months prior to study.

7. 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.

8. Male participants must use condoms during the study and through study completion.

Exclusion Criteria:

1. Treatment with an experimental compound within 30 days.

2. Treatment within 30 days or planned use within the study period with immunomodulator or immunosuppressant agent.

3. Pregnancy or breastfeeding.

4. Presence of any of the following clinical conditions:

   1. 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).
   2. History of venous thromboembolic disease within 12 months, myocardial infarction, or cerebrovascular accident.
   3. Unstable pulmonary, renal, hepatic, endocrine or hematologic disease.
   4. Gastrointestinal disorder requiring ongoing care by a physician.
   5. Autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to rheumatoid arthritis.
   6. 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).
   7. 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.
   8. Positive serology for human immunodeficiency virus (HIV) infection or history of other immunodeficiency illness.
   9. Positive serology results for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
   10. Significant neuromuscular disease or neuropathy
   11. Psychiatric condition
   12. Alcohol or illicit drug abuse/dependency or positive urine toxicology screen for drugs of abuse other than marijuana. Alcohol and tobacco consumption are permitted.