Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this first-in-human (FIH) study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GL-0719 following single intravenous (IV) and subcutaneous injection (SC) doses in healthy adult male and female subjects.

Official Title
-----------------
GL-0719 - A Phase 1, Double-blind, Placebo-controlled, Single Ascending Intravenous and Subcutaneous Injection Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects

Conditions
-----------------
First in Man Study to Evaluate Initial Safety

Intervention / Treatment
-----------------
* Drug: GL-0719
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy female or male subjects who, at the time of screening, are between the ages of 18 and 65 years, inclusive. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception. Body mass index of 18.0 to 32.0 kg/m^2, inclusive; and a total body weight > 50 kg up to a maximum of 110 kg. Study subjects must have received a quadrivalent meningococcal conjugate vaccine (meningococcal serogroups A, C, W, and Y) within the past 5 years or vaccination a minimum of 14 days prior to initial study drug administration. The subject must be capable of understanding the investigational nature, potential risks and benefits of the study and capable of providing valid informed consent. The subject must be willing to return to the study center for study treatment and study-related follow-up procedures as required by the protocol. Exclusion Criteria: History of any clinically significant (as determined by the investigator) cardiac, endocrine, hematological, hepatic, immunological, metabolic, urological, pulmonary, neurological, dermatological, psychiatric, renal, or other major disease. Evidence of clinically significant medical condition or other condition that might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the subject at an unacceptable risk as a participant in this study. Signs and symptoms of, or diagnosis consistent with a chronic autoimmune disorder and/or positive antinuclear antibodies (ANA) test by indirect immunofluorescence confirmed by ANA titer ≥ 1:160. Documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy. Any underlying medical condition that, in the opinion of the investigator, renders the subject a poor candidate for this study or could confound the results of the study or put the subject at undue risk. Concurrent medical condition requiring the chronic concurrent use of systemic steroids or immunosuppressants. Subjects with ANY of the following abnormalities in clinical laboratory tests at screening or on admission, as assessed by the study-specific laboratory and confirmed by a single repeat tests, if deemed necessary: Aspartate aminotransferase or alanine aminotransferase level >1.25 × upper limit of normal (ULN). Total bilirubin level > ULN; subjects with a history of Gilberts syndrome will not be eligible for the study. Serum creatinine levels > ULN. Estimated glomerular filtration rate of < 80 mL/min/1.73m^2 (screening only) calculated using the Modification of Diet in Renal Disease (MDRD) equation. Any history of thromboembolic events or coagulopathy. Diagnosis of a malignancy except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the subject has been disease-free for ≥ 5 years. Active infection or other immunocompromising condition requiring IV treatment within 28 days of study treatment on Day 1. Prior splenectomy or organ allograft. Other protocol defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GL-0719<br>Dose level cohorts randomized in a 3:1 ratio to GL-0719 or placebo treatment, respectively. The study will comprise a single-dose, sequential-group design. Single Ascending IV Dose Cohorts Cohort 1: 4 subjects Cohort 2: 8 subjects Cohort 3: 8 subjects Cohort 4: 8 subjects Cohort 5: 8 subjects Subcutaneous Injection Cohort Cohort 6: 8 subjects Cohort 7: 8 subjects | Drug: GL-0719<br>* Administration route: intravenous infusion and subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>Dose level cohorts randomized in a 3:1 ratio to GL-0719 or placebo treatment, respectively. The study will comprise a single-dose, sequential-group design. Single Ascending IV Dose Cohorts Cohort 1: 4 subjects Cohort 2: 8 subjects Cohort 3: 8 subjects Cohort 4: 8 subjects Cohort 5: 8 subjects Subcutaneous Injection Cohort Cohort 6: 8 subjects Cohort 7: 8 subjects | Drug: Placebo<br>* Administration route: intravenous infusion and subcutaneous injection<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs) |  | Day 1 to Follow-up (Day 31±2) | 
| Incidence of laboratory abnormalities, based on hematology, clinical chemistry, and urinalysis test results |  | Screening (Days -42 to -15) to Follow-up (Day 31±2) | 
| Incidence of abnormal clinical laboratory findings in 12-lead ECG parameters, vital signs, physical examination and measurement of cytokines |  | Screening (Days -42 to -15) to Follow-up (Day 31±2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration time Curve from Time 0 Extrapolated to Infinity (AUC0-∞) |  | Day 1 to Follow-up (Day 31±2) | 
| Area Under the Concentration time Curve from Time 0 to the Time of the Last (AUC0-tlast) |  | Day 1 to Follow-up (Day 31±2) | 
| Maximum Observed Concentration (Cmax) |  | Day 1 to Follow-up (Day 31±2) | 
| Time of the maximum observed concentration (tmax) |  | Day 1 to Follow-up (Day 31±2) | 
| Apparent terminal elimination half-life (t1/2) |  | Day 1 to Follow-up (Day 31±2) | 
| The degree of complement classical pathway inhibition in study subjects over time as evaluated by the MicroVue CH50 Eq EIA assay |  | Day 1 to Follow-up (Day 31±2) | 
| Incidence of anti-drug antibodies |  | Day -1, Day 15±1 and Follow-up (Day 31±2) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
complement-mediated diseases