Back to resultsSafety, Tolerability, PK, PD and Preliminary Efficacy of ONO-4685
Primary Purpose
Plaque Psoriasis
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ONO-4685
Placebo
ONO-4685
Placebo
ONO-4685
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Plaque Psoriasis focused on measuring Psoriasis, ONO-4685, PD-1, Bi-specific antibody, PD-1 Receptor, PD-1 Agonist
Eligibility Criteria
Inclusion Criteria
- Subjects must be willing and able to participate in the study
- A diagnosis of plaque-type psoriasis for ≥6 months.
- Plaque-type psoriasis involving ≥3% of body surface area (BSA) (Parts B and C).
- Willing to provide skin biopsies (Parts B and C).
- Subjects in good health, as judged by medical history, medical examination, vital signs, ECG and clinical laboratory tests.
- Subjects willing to comply with the contraception and sperm and ova donation requirements of the protocol.
Exclusion Criteria
- Subjects with any clinically significant abnormality in screening tests.
- Guttate, erythrodermic or pustular psoriasis as sole or predominant form of the psoriasis, or other skin condition (eg eczema).
- Presence or history of alcohol or drugs abuse.
- Heavy smokers (more than 20 cigarettes or use more than ½ ounce (12.5 grams) of tobacco each day).
- Subjects have had any 'live' vaccines (excluding COVID-19 vaccine) during the 3 months before the first dose of study medicine.
- Subjects have had a first COVID-19 vaccine within 6 weeks or second and booster COVID-19 vaccinations within 2 weeks before the first dose of study medicine.
- Subjects have had any clinically significant disease or infection, including tuberculosis.
- Presence or history of malignancy (cancer) including lymphoproliferative disorders.
- Subject is pregnant, lactating, or breastfeeding.
- Subjects have received treatment with biologics in the last 3 months, immunosuppressant medicine or prescription medicine for psoriasis within 4 weeks before admission to the ward; have used phototherapy from 2 weeks before admission to the ward; have used highly potent or potent topical steroids within 2 weeks before admission to the ward.
- Subjects have used topical corticosteroids or Vitamin D analogues within 7 days before admission to the ward (Parts B and C).
Sites / Locations
- Arensia Exploratory Medicine Phase 1 UnitRecruiting
- Arensia Exploratory Medicine
- Hammersmith Medicines Research
- Medicines Evaluation Unit
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Part A, Active
Part A, Placebo
Part B, Active
Part B, Placebo
Part C, Active
Part C, Placebo
Arm Description
Outcomes
Primary Outcome Measures
Treatment emergent adverse events (TEAEs) by severity
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
Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis).
Cytokines
Number of participants with elevated cytokines.
Lymphocytes
Number of participants with depleted lymphocytes.
Vital signs (blood pressure)
Number of participants with clinically significant changes in vital signs (blood pressure)
Vital signs (respiration rate)
Number of participants with clinically significant changes in vital signs (respiration rate)
Vital signs (temperature)
Number of participants with clinically significant changes in vital signs (temperature)
Vital signs (pulse rate)
Number of participants with clinically significant changes in vital signs (pulse rate)
ECG parameters
Number of participants with ECG abnormalities.
Secondary Outcome Measures
Pharmacokinetics (Ceoi)
Assessment of the observed plasma concentration of ONO-4685 at the end of infusion (eoi).
Pharmacokinetics, Cmax
Assessment of the maximum observed plasma concentration of ONO-4685.
Pharmacokinetics, Tmax
Assessment of the time of maximum plasma concentration of ONO-4685.
Pharmacokinetics, AUC last
Assessment of the area under the plasma ONO-4685 concentration-time curve from time 0 to time of the last quantifiable concentration.
Pharmacokinetics, AUCinf
Assessment of the area under the plasma ONO-4685 concentration-time curve from time 0 to infinity.
Pharmacokinetics, CL (Clearance)
Assessment of the plasma clearance of ONO-4685.
Pharmacokinetics, Vss
Assessment of the volume of distribution at steady state of ONO-4685
Pharmacokinetics, T1/2
Assessment of the terminal elimination half-life of ONO-4685 in plasma.
Pharmacokinetics, AUCtau
Assessment of the area under the plasma ONO-4685 concentration-time curve during the dosing interval.
Pharmacokinetics, Ctrough
Assessment of the trough concentration of ONO-4685 in plasma.
Pharmacodynamics, lymphocytes
Assessment of total lymphocytes, including subsets CD4+ T cell, CD8+ T cell, B cell and NK cell.
Pharmacodynamics, immunoglobulin
Assessment of total immunoglobulin, IgA, IgG and IgM.
Pharmacodynamics, cytokines
Assessment of cytokines, including IL-2, IL-6, IL-10, TNF-α and INF-γ.
Immunogenicity, Anti-ONO-4685-antibodies (ADA)
Assessment of antibodies generated to ONO-4685 to measure potential immunogenicity.
Efficacy, Psoriasis Area and Severity Index (PASI)
Assessment of change in PASI from baseline.
Efficacy, Psoriasis Area and Severity Index (PASI) 50
Assessment of number of subjects that achieve PASI 50, a 50% reduction in PASI from baseline.
Efficacy, Psoriasis Area and Severity Index (PASI) 75
Assessment of number of subjects that achieve PASI 75, a 75% reduction in PASI from baseline.
Efficacy, Psoriasis Area and Severity Index (PASI) 90
Assessment of number of subjects that achieve PASI 90, a 90% reduction in PASI from baseline.
Efficacy, Target Plaque Severity Score (TPSS)
Assessment of change in TPSS from baseline.
Efficacy, Physician's Global Assessment (PGA)
Assessment of change in PGA from baseline.
Efficacy, Physician's Global Assessment (PGA) 0/1
Assessment of the number of subjects that achieve PGA 0/1.
Efficacy, Physician's Global Assessment (PGA) 0/1 and a 2-point improvement
Assessment of the number of subjects that achieve PGA 0/1 and a 2-point improvement from baseline.
Efficacy, Body Surface Area (BSA)
Assessment of the change in plaque BSA from baseline
Patient Reported Outcome, Dermatology Life Quality Index (DLQI)
Assessment of the change in DLQI from baseline.
Full Information
NCT ID
NCT05332704
First Posted
March 18, 2022
Last Updated
August 23, 2023
Sponsor
Ono Pharmaceutical Co. Ltd
1. Study Identification
Unique Protocol Identification Number
NCT05332704
Brief Title
Safety, Tolerability, PK, PD and Preliminary Efficacy of ONO-4685
Official Title
A Randomised, Multi-centre, Double-blind, Placebo-controlled, Single Ascending Dose, Multiple Dose Study to Assess Safety, Tolerability, PK, PD & Preliminary Efficacy of IV Doses of ONO-4685 in Patients With Plaque Psoriasis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 25, 2022 (Actual)
Primary Completion Date
October 24, 2024 (Anticipated)
Study Completion Date
December 18, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ono Pharmaceutical Co. Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plaque Psoriasis
Keywords
Psoriasis, ONO-4685, PD-1, Bi-specific antibody, PD-1 Receptor, PD-1 Agonist
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
This is a phase I, multi-centre study to assess the safety, tolerability, PK & PD of ONO-4685. This study consists of: Part A single ascending dose, Part B an assessment of multiple doses & Part C to undertake initial assessment of efficacy with multiple doses.
The study will recruit patients, male & female, with mild or moderate psoriasis diagnosed for at least 6 months. Following screening activities, patients are admitted to a clinical unit 1 day ahead of dosing and will stay at the unit for 4 nights. For patients receiving multiple doses, they will attend the clinic on the day of dosing and will stay for 3 nights. All patients will be followed up, for up to 24 weeks from 1st dose.
The study will recruit 6 patients per cohort for part A & B and 18 patients per cohort for part C. The overall active to placebo ratio will be 2:1.
Masking
ParticipantInvestigator
Masking Description
This is a double-blind study.
The pharmacist will be unblinded and is responsible for preparing blinded drug for administration.
Allocation
Randomized
Enrollment
74 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part A, Active
Arm Type
Experimental
Arm Title
Part A, Placebo
Arm Type
Placebo Comparator
Arm Title
Part B, Active
Arm Type
Experimental
Arm Title
Part B, Placebo
Arm Type
Placebo Comparator
Arm Title
Part C, Active
Arm Type
Experimental
Arm Title
Part C, Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ONO-4685
Intervention Description
-Part A: Single ascending doses of ONO-4685 as a single IV dose (Cohort A1-A5).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
-Part A: Single ascending doses of placebo as a single IV dose (Cohort A1-A5).
Intervention Type
Drug
Intervention Name(s)
ONO-4685
Intervention Description
-Part B: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort B1 and B2)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
-Part B: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort B1 and B2).
Intervention Type
Drug
Intervention Name(s)
ONO-4685
Intervention Description
-Part C: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort C1 and C2).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
-Part C: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort C1 and C2).
Primary Outcome Measure Information:
Title
Treatment emergent adverse events (TEAEs) by severity
Description
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.
Time Frame
End of Study (3 years)
Title
Clinical laboratory tests
Description
Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis).
Time Frame
End of Study (3 years)
Title
Cytokines
Description
Number of participants with elevated cytokines.
Time Frame
Up to day 8 post dosing day
Title
Lymphocytes
Description
Number of participants with depleted lymphocytes.
Time Frame
End of Study (3 years)
Title
Vital signs (blood pressure)
Description
Number of participants with clinically significant changes in vital signs (blood pressure)
Time Frame
End of Study (3 years)
Title
Vital signs (respiration rate)
Description
Number of participants with clinically significant changes in vital signs (respiration rate)
Time Frame
End of Study (3 years)
Title
Vital signs (temperature)
Description
Number of participants with clinically significant changes in vital signs (temperature)
Time Frame
End of Study (3 years)
Title
Vital signs (pulse rate)
Description
Number of participants with clinically significant changes in vital signs (pulse rate)
Time Frame
End of Study (3 years)
Title
ECG parameters
Description
Number of participants with ECG abnormalities.
Time Frame
End of Study (3 years)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (Ceoi)
Description
Assessment of the observed plasma concentration of ONO-4685 at the end of infusion (eoi).
Time Frame
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.
Title
Pharmacokinetics, Cmax
Description
Assessment of the maximum observed plasma concentration of ONO-4685.
Time Frame
Part A up to day 85, Part B and Part C up to day 113
Title
Pharmacokinetics, Tmax
Description
Assessment of the time of maximum plasma concentration of ONO-4685.
Time Frame
Part A up to day 85, Part B and Part C up to day 113
Title
Pharmacokinetics, AUC last
Description
Assessment of the area under the plasma ONO-4685 concentration-time curve from time 0 to time of the last quantifiable concentration.
Time Frame
Part A up to day 85
Title
Pharmacokinetics, AUCinf
Description
Assessment of the area under the plasma ONO-4685 concentration-time curve from time 0 to infinity.
Time Frame
Part A up to day 85
Title
Pharmacokinetics, CL (Clearance)
Description
Assessment of the plasma clearance of ONO-4685.
Time Frame
Part A up to day 85
Title
Pharmacokinetics, Vss
Description
Assessment of the volume of distribution at steady state of ONO-4685
Time Frame
Part A up to day 85
Title
Pharmacokinetics, T1/2
Description
Assessment of the terminal elimination half-life of ONO-4685 in plasma.
Time Frame
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.
Title
Pharmacokinetics, AUCtau
Description
Assessment of the area under the plasma ONO-4685 concentration-time curve during the dosing interval.
Time Frame
Part B and C, after first (Day 1) and last (Day 15 or 22) dose
Title
Pharmacokinetics, Ctrough
Description
Assessment of the trough concentration of ONO-4685 in plasma.
Time Frame
Part B and C, prior to administration of each dose
Title
Pharmacodynamics, lymphocytes
Description
Assessment of total lymphocytes, including subsets CD4+ T cell, CD8+ T cell, B cell and NK cell.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Pharmacodynamics, immunoglobulin
Description
Assessment of total immunoglobulin, IgA, IgG and IgM.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Pharmacodynamics, cytokines
Description
Assessment of cytokines, including IL-2, IL-6, IL-10, TNF-α and INF-γ.
Time Frame
Part A up to day 8, Part B and Part C up to day 8 post last dose
Title
Immunogenicity, Anti-ONO-4685-antibodies (ADA)
Description
Assessment of antibodies generated to ONO-4685 to measure potential immunogenicity.
Time Frame
Part A up to day 85, Part B and Part C up to day 113
Title
Efficacy, Psoriasis Area and Severity Index (PASI)
Description
Assessment of change in PASI from baseline.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Efficacy, Psoriasis Area and Severity Index (PASI) 50
Description
Assessment of number of subjects that achieve PASI 50, a 50% reduction in PASI from baseline.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Efficacy, Psoriasis Area and Severity Index (PASI) 75
Description
Assessment of number of subjects that achieve PASI 75, a 75% reduction in PASI from baseline.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Efficacy, Psoriasis Area and Severity Index (PASI) 90
Description
Assessment of number of subjects that achieve PASI 90, a 90% reduction in PASI from baseline.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Efficacy, Target Plaque Severity Score (TPSS)
Description
Assessment of change in TPSS from baseline.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Efficacy, Physician's Global Assessment (PGA)
Description
Assessment of change in PGA from baseline.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Efficacy, Physician's Global Assessment (PGA) 0/1
Description
Assessment of the number of subjects that achieve PGA 0/1.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Efficacy, Physician's Global Assessment (PGA) 0/1 and a 2-point improvement
Description
Assessment of the number of subjects that achieve PGA 0/1 and a 2-point improvement from baseline.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Efficacy, Body Surface Area (BSA)
Description
Assessment of the change in plaque BSA from baseline
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
Title
Patient Reported Outcome, Dermatology Life Quality Index (DLQI)
Description
Assessment of the change in DLQI from baseline.
Time Frame
Part A up to day 85, Part B up to day 113, Part C up to day 169
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Subjects must be willing and able to participate in the study
A diagnosis of plaque-type psoriasis for ≥6 months.
Plaque-type psoriasis involving ≥3% of body surface area (BSA) (Parts B and C).
Willing to provide skin biopsies (Parts B and C).
Subjects in good health, as judged by medical history, medical examination, vital signs, ECG and clinical laboratory tests.
Subjects willing to comply with the contraception and sperm and ova donation requirements of the protocol.
Exclusion Criteria
Subjects with any clinically significant abnormality in screening tests.
Guttate, erythrodermic or pustular psoriasis as sole or predominant form of the psoriasis, or other skin condition (eg eczema).
Presence or history of alcohol or drugs abuse.
Heavy smokers (more than 20 cigarettes or use more than ½ ounce (12.5 grams) of tobacco each day).
Subjects have had any 'live' vaccines (excluding COVID-19 vaccine) during the 3 months before the first dose of study medicine.
Subjects have had a first COVID-19 vaccine within 6 weeks or second and booster COVID-19 vaccinations within 2 weeks before the first dose of study medicine.
Subjects have had any clinically significant disease or infection, including tuberculosis.
Presence or history of malignancy (cancer) including lymphoproliferative disorders.
Subject is pregnant, lactating, or breastfeeding.
Subjects have received treatment with biologics in the last 3 months, immunosuppressant medicine or prescription medicine for psoriasis within 4 weeks before admission to the ward; have used phototherapy from 2 weeks before admission to the ward; have used highly potent or potent topical steroids within 2 weeks before admission to the ward.
Subjects have used topical corticosteroids or Vitamin D analogues within 7 days before admission to the ward (Parts B and C).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ono Pharma UK Ltd
Email
trials.uk-eu@ono-pharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Project Leader
Organizational Affiliation
Ono Pharmaceutical Co. Ltd
Official's Role
Study Director
Facility Information:
Facility Name
Arensia Exploratory Medicine Phase 1 Unit
City
Chisinau
ZIP/Postal Code
MD-2025
Country
Moldova, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lilia Taran
Facility Name
Arensia Exploratory Medicine
City
Bucharest
ZIP/Postal Code
011658
Country
Romania
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olguta Orzan
Facility Name
Hammersmith Medicines Research
City
London
ZIP/Postal Code
NW10 7EW
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adeep Puri
Facility Name
Medicines Evaluation Unit
City
Manchester
ZIP/Postal Code
M23 9QZ
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naimat Khan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing URL
https://www.ono-pharma.com/en/company/policies/clinical_trial_data_transparency_policy.html
Learn more about this trial
Safety, Tolerability, PK, PD and Preliminary Efficacy of ONO-4685
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