Rheumatoid Arthritis
Conditions
Keywords
RA, Rheumatoid Arthritis, Healthy Participants, Phase 1a/1b, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, First in human, Single Ascending Dose, Multiple Ascending Dose
Brief summary
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.
Interventions
DRUGLFD-200
2 mL glass vials, as 150 mg/mL concentrated solution
OTHERPlacebo
0.9% NaCl
DRUGOral Prednisone
Tablet
Sponsors
Lifordi Immunotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
for Healthy Participants: * Age 18-55 * BMI - 18-32 * Participants must be deemed by the Investigator to be generally healthy individuals based on a medical evaluation that includes a physical examination, medical history, vital signs, and the results from clinical labs and other safety assessments collected during the Screening period.
Exclusion criteria
for Healthy Participants: * Participants with any current or previous illness that, in the opinion of the investigator, might confound the results of the study or pose an additional, unacceptable risk to the participant or that could prevent, limit, or confound the protocol specified assessments or study results' interpretation. * Recent serious or ongoing infection * Known/suspected primary immunodeficiency * Receipt of injected or systemic glucocorticoids within 6 weeks prior to screening * Use of prohibited medications * Any of the following lab abnormalities: * White blood cell (WBC) count \<3.0 x 109/L * Absolute neutrophil count (ANC) \<2.0 x 109/L * Hemoglobin (Hgb) \<12.5 g/dL for males and \<11.5 g/dL for females * Platelet count \<140 x 109/L * Alanine transaminase (ALT) ≥1.2x upper limit of normal (ULN) * Total bilirubin ≥1.2x ULN (except if Gilbert's disease is suspected etiology) * Estimated glomerular filtration rate (eGFR) \<80 mL/min/1.73m2 based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) formula. * International normalized ratio (INR) ≥1.2 × ULN * Glycated hemoglobin (HbA1c) \>6% * Positive urine cotinine test (Day -1 only), alcohol breath test or urine drug screen for substances of abuse. Positive tetrahydrocannabinol (THC) is not exclusionary. * A Screening thyroid stimulating hormone (TSH) level that is \<0.9 × lower limit normal (LLN) or ≥1.2 × ULN * Cortisol level \<1.0 × LLN (Collected in the AM at the Baseline Visit) Inclusion Criteria for RA Participants: * Adults of age 18 to 75 years, inclusive, at the time of signing the ICF. * BMI within the range of 18.0- to 35.0 kg/m² (inclusive). * Has RA for ≥6 months. * Positive rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) test at Screening (low or high positive acceptable). * A high-sensitivity C-reactive protein (hsCRP) level at Screening must be \>ULN. * Has active RA disease defined as follows: * Disease Activity Score of 28 joints-CRP (DAS28-CRP) \>3.2 at Screening and Baseline * Has ≥4 swollen and ≥4 tender joints on a 28-joint count at Screening and Baseline * On MTX orally or subcutaneously for at least 12 weeks prior to Screening. Dose of MTX (including route of administration) must have been stable at 15 to 25 mg weekly (or 10 to15mg in case of documented intolerance) for ≥ 12weeks at Randomization with plans to continue it at the same dose and route of administration for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) | Baseline up to 30 days after last dose. | Number of participants experiencing any adverse events during the study period. |
| Severity of Adverse Events (AEs) | Baseline up to 30 days after last dose. | Classification of adverse events based on severity (mild, moderate, severe). |
| Seriousness of Adverse Events (AEs) | Baseline up to 30 days after last dose. | Number of participants experiencing serious adverse events (SAEs) during the study period. |
| Change from Baseline in Blood Pressure (BP) | Baseline up to 30 days after last dose. | Difference in systolic and diastolic blood pressure measurements from baseline to specified time points. |
| Change from Baseline in Temperature | Baseline up to 30 days after last dose. | Difference in body temperature measurements from baseline to specified time points. |
| Change from Baseline in Respiratory Rate | Baseline up to 30 days after last dose. | Difference in respiratory rate measurements from baseline to specified time points. |
| Change from Baseline in Heart Rate (HR) | Baseline up to 30 days after last dose. | Difference in heart rate measurements from baseline to specified time points. |
| Change in Hemeglobin from Baseline to specified timepoints | Baseline up to 30 days after last dose. | Hemeglobin is measured in g/dL |
| Change in Alanine Aminotransferase from Baseline to specified timepoints | Baseline up to 30 days after last dose. | Alanine Aminotransferase is measured in U/L |
| Change in Leukocytes in urine from Baseline to specified timepoints | Baseline up to 30 days after last dose. | Leukocytes in urine is measured in x10\^6/L |
| Change in Heart Rate (HR) from Baseline to specified timepoints | Baseline up to 30 days after last dose. | Heart rate is measured in beats per minute |
| Change from Baseline in PR Interval | Baseline up to 30 days after last dose. | Difference in PR interval measurements from baseline to specified time points. |
| Change from Baseline in QRS Interval | Baseline up to 30 days after last dose. | Difference in QRS interval measurements from baseline to specified time points. |
| Change from Baseline in QT Interval | Baseline up to 30 days after last dose. | Difference in QT interval measurements from baseline to specified time points. |
| Primary Outcome Measure: Change from Baseline in QTcF Interval | Baseline up to 30 days after last dose. | Difference in QTcF interval measurements from baseline to specified time points. |
| Incidence of Clinical Findings on Physical Examination | Baseline up to 30 days after last dose. | Number of participants with clinical findings during physical examinations, including injection site reactions. |
| Severity of Clinical Findings on Physical Examination | Baseline up to 30 days after last dose. | Classification of clinical findings based on severity (mild, moderate, severe), including injection site reactions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Baseline up to 30 days after last dose. | The highest concentration of the drug observed in plasma after administration. |
| Trough Concentration (Ctrough) | Baseline up to 30 days after last dose. | The lowest concentration of the drug observed in plasma before the next dose. |
| Average Concentration (Cavg) | Baseline up to 30 days after last dose. | The average concentration of the drug in plasma over a specified time period |
| Clearance | Baseline up to 30 days after last dose. | The rate at which the drug is removed from the body. |
| Volume of Distribution | Baseline up to 30 days after last dose. | The volume in which the drug is distributed in the body. |
| Area Under the Plasma Concentration vs. Time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) | Baseline up to 30 days after last dose. | The area under the plasma concentration-time curve from the time of dosing to the last measurable concentration. |
| Area Under the Plasma Concentration vs. Time Curve from Time Zero Extrapolated to Infinity (AUCinf) | Baseline up to 30 days after last dose. | The area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. |
| Area Under the Plasma Concentration vs. Time Curve from Time Zero to 168 Hours Post-Dose (AUC0-168) | Baseline up to 30 days after last dose. | The area under the plasma concentration-time curve from the time of dosing to 168 hours post-dose. |
| Area Under the Plasma Concentration vs Time Curve Over the Dosing Interval (AUCtau) | Baseline up to 30 days after last dose. | The area under the plasma concentration-time curve over the dosing interval. |
| Accumulation Ratio (Rac) | Baseline up to 30 days after last dose. | The ratio of drug accumulation in plasma after multiple dosing compared to a single dose. |
| Time Corresponding to the Maximum Observed Plasma Concentration (Tmax) | Baseline up to 30 days after last dose. | The time at which the maximum plasma concentration of the drug is observed. |
| Change from Baseline in Cortisol Levels | Baseline up to 30 days after last dose. | Difference in cortisol levels from baseline to specified time points. |
| Change from Baseline in Bone Biomarkers | Baseline up to 30 days after last dose. | Difference in Bone Biomarker levels from baseline to specified time points |
| Change from Baseline in DAS28-CRP | Baseline up to 30 days after last dose. | Difference in Disease Activity Score 28 - C-reactive protein (DAS28-CRP) from baseline to specified time points for rheumatoid arthritis (RA) cohorts. |
Countries
Australia, Georgia, Moldova, Poland, Ukraine
Contacts
CONTACTMatthew McClure, MD
Outcome results
None listed