Safety, Tolerability, PK, PD and Preliminary Efficacy of ONO-4685
- Registration Number
- NCT05332704
- Lead Sponsor
- Ono Pharmaceutical Co. Ltd
- Brief Summary
This is an early phase study to assess the safety and tolerability of ONO-4685 in patients with psoriasis. In addition, the study will assess how the drug is distributed and eliminated by the body (pharmacokinetics) and how the drug affects the body (pharmacodynamics). This will be done by measuring the amount of drug in the blood and measuring other markers in the body that might have been affected by ONO-4685. The study will also look at preliminary information on whether ONO-4685 might be effective in treating psoriasis.
The study will be split into three parts. Part A will assess a single dose of ONO-4685 in small groups of patients, each group planned to receive a higher dose than the last group. In Part B and C, patients will receive multiple doses of ONO-4685 over a period of 4 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 33
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A, Active ONO-4685 - Part A, Placebo Placebo - Part B, Placebo Placebo - Part B, Active ONO-4685 - Part C, Active ONO-4685 - Part C, Placebo Placebo -
- Primary Outcome Measures
Name Time Method Treatment emergent adverse events (TEAEs) by severity End of Study (3 years) Number of participants with TEAEs. An adverse event is any untoward medical occurrence in a participant who receives study drug without regard to possible causal relationship.
Clinical laboratory tests End of Study (3 years) Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis).
Cytokines Up to day 8 post dosing day Number of participants with elevated cytokines.
Lymphocytes End of Study (3 years) Number of participants with depleted lymphocytes.
Vital signs (blood pressure) End of Study (3 years) Number of participants with clinically significant changes in vital signs (blood pressure)
Vital signs (temperature) End of Study (3 years) Number of participants with clinically significant changes in vital signs (temperature)
Vital signs (respiration rate) End of Study (3 years) Number of participants with clinically significant changes in vital signs (respiration rate)
Vital signs (pulse rate) End of Study (3 years) Number of participants with clinically significant changes in vital signs (pulse rate)
ECG parameters End of Study (3 years) Number of participants with ECG abnormalities.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics, AUC last Part A up to day 85 Assessment of the area under the plasma ONO-4685 concentration-time curve from time 0 to time of the last quantifiable concentration.
Pharmacokinetics, AUCinf Part A up to day 85 Assessment of the area under the plasma ONO-4685 concentration-time curve from time 0 to infinity.
Pharmacokinetics, Cmax Part A up to day 85, Part B and Part C up to day 113 Assessment of the maximum observed plasma concentration of ONO-4685.
Pharmacokinetics, Tmax Part A up to day 85, Part B and Part C up to day 113 Assessment of the time of maximum plasma concentration of ONO-4685.
Pharmacokinetics (Ceoi) Part A, Day 1 (day of dosing). Part B and C, Day 1 (day of first dose) and Day 15 or 22 (day of last dose) depending on weekly or bi-weekly dosing. Assessment of the observed plasma concentration of ONO-4685 at the end of infusion (eoi).
Pharmacokinetics, T1/2 Part A up to day 85, and after the last dose administration (Day 15 or 22) in Part B and Part C up to day 113. Assessment of the terminal elimination half-life of ONO-4685 in plasma.
Pharmacokinetics, AUCtau Part B and C, after first (Day 1) and last (Day 15 or 22) dose Assessment of the area under the plasma ONO-4685 concentration-time curve during the dosing interval.
Pharmacodynamics, cytokines Part A up to day 8, Part B and Part C up to day 8 post last dose Assessment of cytokines, including IL-2, IL-6, IL-10, TNF-α and INF-γ.
Immunogenicity, Anti-ONO-4685-antibodies (ADA) Part A up to day 85, Part B and Part C up to day 113 Assessment of antibodies generated to ONO-4685 to measure potential immunogenicity.
Efficacy, Psoriasis Area and Severity Index (PASI) Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of change in PASI from baseline.
Efficacy, Psoriasis Area and Severity Index (PASI) 50 Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of number of subjects that achieve PASI 50, a 50% reduction in PASI from baseline.
Efficacy, Psoriasis Area and Severity Index (PASI) 75 Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of number of subjects that achieve PASI 75, a 75% reduction in PASI from baseline.
Efficacy, Psoriasis Area and Severity Index (PASI) 90 Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of number of subjects that achieve PASI 90, a 90% reduction in PASI from baseline.
Efficacy, Target Plaque Severity Score (TPSS) Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of change in TPSS from baseline.
Efficacy, Physician's Global Assessment (PGA) Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of change in PGA from baseline.
Efficacy, Physician's Global Assessment (PGA) 0/1 Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of the number of subjects that achieve PGA 0/1.
Pharmacokinetics, CL (Clearance) Part A up to day 85 Assessment of the plasma clearance of ONO-4685.
Pharmacokinetics, Vss Part A up to day 85 Assessment of the volume of distribution at steady state of ONO-4685
Pharmacokinetics, Ctrough Part B and C, prior to administration of each dose Assessment of the trough concentration of ONO-4685 in plasma.
Pharmacodynamics, immunoglobulin Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of total immunoglobulin, IgA, IgG and IgM.
Pharmacodynamics, lymphocytes Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of total lymphocytes, including subsets CD4+ T cell, CD8+ T cell, B cell and NK cell.
Efficacy, Physician's Global Assessment (PGA) 0/1 and a 2-point improvement Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of the number of subjects that achieve PGA 0/1 and a 2-point improvement from baseline.
Efficacy, Body Surface Area (BSA) Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of the change in plaque BSA from baseline
Patient Reported Outcome, Dermatology Life Quality Index (DLQI) Part A up to day 85, Part B up to day 113, Part C up to day 169 Assessment of the change in DLQI from baseline.
Trial Locations
- Locations (4)
Arensia Exploratory Medicine Phase 1 Unit
🇲🇩Chisinau, Moldova, Republic of
Arensia Exploratory Medicine
🇷🇴Bucharest, Romania
Medicines Evaluation Unit
🇬🇧Manchester, United Kingdom
Hammersmith Medicines Research
🇬🇧London, United Kingdom