This is a double-blind, randomized, placebo- and active-controlled study investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous (SC) doses of LFD-200. The study design includes: a single ascending dose (SAD) study in up to 66 adult healthy participants (HPs) to investigate the effects of a single SC dose, with a 30-day follow-up; a multiple ascending dose (MAD) study in up to 40 HPs to assess up to 4 weekly SC doses, with a 30-day follow-up after the last dose; and a MAD study in up to 70 participants with moderate to severe rheumatoid arthritis (RA) to evaluate up to 13 weekly SC doses, with a 30-day follow-up after the last dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
176
2 mL glass vials, as 150 mg/mL concentrated solution
0.9% NaCl
Tablet
Placebo tablet to match Prednisone
Nucleus Network
Melbourne, Australia
RECRUITINGArensia Exploratory Medicine LLC
Tbilisi, Georgia
RECRUITINGClinical Republican Hospital "Timofei Mosneaga", ARENSIA E.M.
Chisinau, Moldova
RECRUITINGMICS Centrum Medyczne Torun - MICS - PPDS
Torun, Poland
NOT_YET_RECRUITINGCentrum Medyczne Reuma Park
Warsaw, Poland
NOT_YET_RECRUITING"ARENSIA EXPLORATORY MEDICINE" LIMITED LIABILITY COMPANY, Medical Center, Department of Clinical Trials
Kyiv, Ukraine
RECRUITINGIncidence of Adverse Events (AEs)
Number of participants experiencing any adverse events during the study period.
Time frame: Baseline up to 30 days after last dose.
Severity of Adverse Events (AEs)
Classification of adverse events based on severity (mild, moderate, severe).
Time frame: Baseline up to 30 days after last dose.
Seriousness of Adverse Events (AEs)
Number of participants experiencing serious adverse events (SAEs) during the study period.
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in Blood Pressure (BP)
Difference in systolic and diastolic blood pressure measurements from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in Temperature
Difference in body temperature measurements from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in Respiratory Rate
Difference in respiratory rate measurements from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in Heart Rate (HR)
Difference in heart rate measurements from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Change in Hemeglobin from Baseline to specified timepoints
Hemeglobin is measured in g/dL
Time frame: Baseline up to 30 days after last dose.
Change in Alanine Aminotransferase from Baseline to specified timepoints
Alanine Aminotransferase is measured in U/L
Time frame: Baseline up to 30 days after last dose.
Change in Leukocytes in urine from Baseline to specified timepoints
Leukocytes in urine is measured in x10\^6/L
Time frame: Baseline up to 30 days after last dose.
Change in Heart Rate (HR) from Baseline to specified timepoints
Heart rate is measured in beats per minute
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in PR Interval
Difference in PR interval measurements from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in QRS Interval
Difference in QRS interval measurements from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in QT Interval
Difference in QT interval measurements from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Primary Outcome Measure: Change from Baseline in QTcF Interval
Difference in QTcF interval measurements from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Incidence of Clinical Findings on Physical Examination
Number of participants with clinical findings during physical examinations, including injection site reactions.
Time frame: Baseline up to 30 days after last dose.
Severity of Clinical Findings on Physical Examination
Classification of clinical findings based on severity (mild, moderate, severe), including injection site reactions.
Time frame: Baseline up to 30 days after last dose.
Maximum Observed Plasma Concentration (Cmax)
The highest concentration of the drug observed in plasma after administration.
Time frame: Baseline up to 30 days after last dose.
Trough Concentration (Ctrough)
The lowest concentration of the drug observed in plasma before the next dose.
Time frame: Baseline up to 30 days after last dose.
Average Concentration (Cavg)
The average concentration of the drug in plasma over a specified time period
Time frame: Baseline up to 30 days after last dose.
Clearance
The rate at which the drug is removed from the body.
Time frame: Baseline up to 30 days after last dose.
Volume of Distribution
The volume in which the drug is distributed in the body.
Time frame: Baseline up to 30 days after last dose.
Area Under the Plasma Concentration vs. Time Curve from Time Zero to the Last Quantifiable Concentration (AUClast)
The area under the plasma concentration-time curve from the time of dosing to the last measurable concentration.
Time frame: Baseline up to 30 days after last dose.
Area Under the Plasma Concentration vs. Time Curve from Time Zero Extrapolated to Infinity (AUCinf)
The area under the plasma concentration-time curve from the time of dosing extrapolated to infinity.
Time frame: Baseline up to 30 days after last dose.
Area Under the Plasma Concentration vs. Time Curve from Time Zero to 168 Hours Post-Dose (AUC0-168)
The area under the plasma concentration-time curve from the time of dosing to 168 hours post-dose.
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Time frame: Baseline up to 30 days after last dose.
Area Under the Plasma Concentration vs Time Curve Over the Dosing Interval (AUCtau)
The area under the plasma concentration-time curve over the dosing interval.
Time frame: Baseline up to 30 days after last dose.
Accumulation Ratio (Rac)
The ratio of drug accumulation in plasma after multiple dosing compared to a single dose.
Time frame: Baseline up to 30 days after last dose.
Time Corresponding to the Maximum Observed Plasma Concentration (Tmax)
The time at which the maximum plasma concentration of the drug is observed.
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in Cortisol Levels
Difference in cortisol levels from baseline to specified time points.
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in Bone Biomarkers
Difference in Bone Biomarker levels from baseline to specified time points
Time frame: Baseline up to 30 days after last dose.
Change from Baseline in DAS28-CRP
Difference in Disease Activity Score 28 - C-reactive protein (DAS28-CRP) from baseline to specified time points for rheumatoid arthritis (RA) cohorts.
Time frame: Baseline up to 30 days after last dose.