The main purpose of this study is to to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity of LAD191 in healthy adults and in adults with an autoimmune disease.
This is a 3-part study. Part 1 will be comprised of up to 5 cohorts of healthy adult participants and will investigate single ascending doses of LAD191. Part 2 will be comprised of up to 3 cohorts of healthy adult participants and will investigate multiple ascending doses of LAD191. Part 3 will be comprised of single cohort of participants with an autoimmune disease and will investigate repeat doses of LAD191. Each ascending dose level will be investigated by a sequential cohort, with dose escalation based on satisfactory safety, tolerability, PK, PD, immunogenicity, biomarker and clinical response assessments will be performed throughout. Each cohort will be randomized to receive LAD191 and placebo. Each participant will participate for about 14 weeks in Part 1, 17 weeks in Part 2 and 18 weeks in Part 3 of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
69
Doral Medical Research
Miami, Florida, United States
Jennifer Parish, MD
Philadelphia, Pennsylvania, United States
ICON Early Phase Services, LLC
San Antonio, Texas, United States
Part 1: Number of Participants with Adverse Events (AEs) and Severity of AEs
Time frame: Baseline up to Day 73
Part 1: Number of Participants who have Dose-limiting Adverse Reactions
Time frame: Baseline up to Day 73
Part 1: Number of Participants with Clinically Significant Changes from Baseline in Vital Sign Parameter
Time frame: Baseline up to Day 73
Part 1: Number of Participants with Clinically Significant Changes from Baseline in Physical Examination Findings
Time frame: Baseline up to Day 73
Part 1: Number of Participants with Clinically Significant Changes from Baseline in Electrocardiograms (ECGs) Parameters
Time frame: Baseline up to Day 73
Part 1: Number of Participants with Clinically Significant Changes from Baseline in Clinical Laboratory Parameters
Time frame: Baseline up to Day 73
Part 2 and 3: Number of Participants with Adverse Events (AEs) and Severity of AEs
Time frame: Baseline up to Day 94
Part 2 and 3: Number of Participants who have Dose-limiting Adverse Reactions
Time frame: Baseline up to Day 94
Part 2 and 3: Number of Participants with Clinically Significant Changes from Baseline in Vital Sign Parameter
Time frame: Baseline up to Day 94
Part 2 and 3: Number of Participants with Clinically Significant Changes from Baseline in Physical Examination Findings
Time frame: Baseline up to Day 94
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Part 2 and 3: Number of Participants with Clinically Significant Changes from Baseline in ECGs Parameters
Time frame: Baseline up to Day 94
Part 2 and 3: Number of Participants with Clinically Significant Changes from Baseline in Clinical Laboratory Parameters
Time frame: Baseline up to Day 94
Part 1: Maximum Serum Concentration (Cmax) of LAD191
Time frame: Pre-dose, 4 hours and 8 hours post-dose on Days 1, 2, 3, 4, 6, 8, 15, 22, 29, 43, 57 and 71
Part 1: Time to Reach Maximum Serum Concentration (Tmax) of LAD191
Time frame: Pre-dose, 4 hours and 8 hours post-dose on Days 1, 2, 3, 4, 6, 8, 15, 22, 29, 43, 57 and 71
Part 1: Area Under the Serum Concentration-time Curve from Zero to Time of the Last Quantifiable Concentration (AUC0-t) of LAD191
Time frame: Pre-dose, 4 hours and 8 hours post-dose on Days 1, 2, 3, 4, 6, 8, 15, 22, 29, 43, 57 and 71
Part 1: Area Under the Serum Concentration-time Curve from Zero to infinity (AUC0-inf) of LAD191
Time frame: Pre-dose, 4 hours and 8 hours post-dose on Days 1, 2, 3, 4, 6, 8, 15, 22, 29, 43, 57 and 71
Part 1: Elimination Half-life (t½) of LAD191
Time frame: Pre-dose, 4 hours and 8 hours post-dose on Days 1, 2, 3, 4, 6, 8, 15, 22, 29, 43, 57 and 71
Part 1: Apparent Total Serum Clearance (CL/F) of LAD191
Time frame: Pre-dose, 4 hours and 8 hours post-dose on Days 1, 2, 3, 4, 6, 8, 15, 22, 29, 43, 57 and 71
Part 1: Apparent Volume of Distribution Associated with the Terminal Phase (Vd/F) of LAD191
Time frame: Pre-dose, 4 hours and 8 hours post-dose on Days 1, 2, 3, 4, 6, 8, 15, 22, 29, 43, 57 and 71
Part 1: Number of Participants with Positive Anti-drug Antibodies (ADA) and Titer of ADA of LAD191
Time frame: Pre-dose on Day 1; 24 hours post-dose on Days 15; 48 hours post-dose on Days 43 and 71
Part 2: Area Under the Serum Concentration-time Curve from Zero to Time of the Last Quantifiable Concentration (AUC0-t) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Area Under the Concentration-time Curve within a Dosing Interval (AUCτau) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Maximum Serum Concentration (Cmax) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Time to Reach Maximum Serum Concentration (Tmax) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Minimum Serum Concentrations (Cmin) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Time to Cmin (tmin) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Area Under the Serum Concentration-time Curve from Zero to Time of the Last Quantifiable Concentration (AUC0-t) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Area Under the Concentration-time Curve within a Dosing Interval (AUCτau) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Maximum Serum Concentration (Cmax) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Time to Reach Maximum Serum Concentration (Tmax) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Minimum Serum Concentrations (Cmin) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Time to Cmin (tmin) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Apparent Total Serum Clearance (CL/F) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Apparent Volume of Distribution Associated with the Terminal Phase (Vd/F) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Elimination Half-life (t½) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2: Accumulation Ratios Based on AUC (R[AUC]) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours, 24 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 2 and 3: Number of Participants with Positive ADA and Titer of ADA of LAD191
Time frame: Pre-dose on Days 1, 15, and 29; 4 hours post-dose on Days 43; 48 hours post-dose on 64 and 92
Part 3: Area Under the Serum Concentration-time Curve from Zero to Time of the Last Quantifiable Concentration (AUC0-t) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Area Under the Concentration-time Curve within a Dosing Interval (AUCτau) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Maximum Serum Concentration (Cmax) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Time to Reach Maximum Serum Concentration (Tmax) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Minimum Serum Concentrations (Cmin) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Time to Cmin (tmin) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Area Under the Serum Concentration-time Curve from Zero to Time of the Last Quantifiable Concentration (AUC0-t) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Area Under the Concentration-time Curve within a Dosing Interval (AUCτau) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Maximum Serum Concentration (Cmax) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Time to Reach Maximum Serum Concentration (Tmax) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Minimum Serum Concentrations (Cmin) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Time to Cmin (tmin) at Steady State of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Apparent Total Serum Clearance (CL/F) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Apparent Volume of Distribution Associated with the Terminal Phase (Vd/F) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Elimination Half-life (t½) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92
Part 3: Accumulation Ratios Based on AUC (R[AUC]) of LAD191
Time frame: Pre-dose at Days 1, 8, 15, 22, 29, and 36; At 4 hours and 48 hours post-dose on Days 1, 36, 40, 43, 50, 64, 85 and 92