Safety, Tolerability, PK, PD and Preliminary Efficacy of ONO-4685

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

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.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: ONO-4685; Drug: Placebo; Drug: ONO-4685; Drug: ONO-4685; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • Arensia Exploratory Medicine Phase 1 Unit
• Romania
  • Bucharest, Romania, 011658
    • Arensia Exploratory Medicine
• United Kingdom
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicines Research
  • Manchester, United Kingdom, M23 9QZ
    • Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A, Active	Drug: ONO-4685; -Part B: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort B1 and B2); Drug: ONO-4685; -Part A: Single ascending doses of ONO-4685 as a single IV dose (Cohort A1-A5).; Drug: ONO-4685; -Part C: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort C1 and C2).
Placebo Comparator: Part A, Placebo	Drug: Placebo; -Part B: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort B1 and B2).; Drug: Placebo; -Part A: Single ascending doses of placebo as a single IV dose (Cohort A1-A5).; Drug: Placebo; -Part C: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort C1 and C2).
Experimental: Part B, Active	Drug: ONO-4685; -Part B: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort B1 and B2); Drug: ONO-4685; -Part A: Single ascending doses of ONO-4685 as a single IV dose (Cohort A1-A5).; Drug: ONO-4685; -Part C: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort C1 and C2).
Placebo Comparator: Part B, Placebo	Drug: Placebo; -Part B: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort B1 and B2).; Drug: Placebo; -Part A: Single ascending doses of placebo as a single IV dose (Cohort A1-A5).; Drug: Placebo; -Part C: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort C1 and C2).
Experimental: Part C, Active	Drug: ONO-4685; -Part B: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort B1 and B2); Drug: ONO-4685; -Part A: Single ascending doses of ONO-4685 as a single IV dose (Cohort A1-A5).; Drug: ONO-4685; -Part C: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort C1 and C2).
Placebo Comparator: Part C, Placebo	Drug: Placebo; -Part B: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort B1 and B2).; Drug: Placebo; -Part A: Single ascending doses of placebo as a single IV dose (Cohort A1-A5).; Drug: Placebo; -Part C: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort C1 and C2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	End of Study (3 years)
Clinical laboratory tests	Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis).	End of Study (3 years)
Cytokines	Number of participants with elevated cytokines.	Up to day 8 post dosing day
Lymphocytes	Number of participants with depleted lymphocytes.	End of Study (3 years)
Vital signs (blood pressure)	Number of participants with clinically significant changes in vital signs (blood pressure)	End of Study (3 years)
Vital signs (respiration rate)	Number of participants with clinically significant changes in vital signs (respiration rate)	End of Study (3 years)
Vital signs (temperature)	Number of participants with clinically significant changes in vital signs (temperature)	End of Study (3 years)
Vital signs (pulse rate)	Number of participants with clinically significant changes in vital signs (pulse rate)	End of Study (3 years)
ECG parameters	Number of participants with ECG abnormalities.	End of Study (3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (Ceoi)	Assessment of the observed plasma concentration of ONO-4685 at the end of infusion (eoi).	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.
Pharmacokinetics, Cmax	Assessment of the maximum observed plasma concentration of ONO-4685.	Part A up to day 85, Part B and Part C up to day 113
Pharmacokinetics, Tmax	Assessment of the time of maximum plasma concentration of ONO-4685.	Part A up to day 85, Part B and Part C up to day 113
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.	Part A up to day 85
Pharmacokinetics, AUCinf	Assessment of the area under the plasma ONO-4685 concentration-time curve from time 0 to infinity.	Part A up to day 85
Pharmacokinetics, CL (Clearance)	Assessment of the plasma clearance of ONO-4685.	Part A up to day 85
Pharmacokinetics, Vss	Assessment of the volume of distribution at steady state of ONO-4685	Part A up to day 85
Pharmacokinetics, T1/2	Assessment of the terminal elimination half-life of ONO-4685 in plasma.	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.
Pharmacokinetics, AUCtau	Assessment of the area under the plasma ONO-4685 concentration-time curve during the dosing interval.	Part B and C, after first (Day 1) and last (Day 15 or 22) dose
Pharmacokinetics, Ctrough	Assessment of the trough concentration of ONO-4685 in plasma.	Part B and C, prior to administration of each dose
Pharmacodynamics, lymphocytes	Assessment of total lymphocytes, including subsets CD4+ T cell, CD8+ T cell, B cell and NK cell.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Pharmacodynamics, immunoglobulin	Assessment of total immunoglobulin, IgA, IgG and IgM.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Pharmacodynamics, cytokines	Assessment of cytokines, including IL-2, IL-6, IL-10, TNF-α and INF-γ.	Part A up to day 8, Part B and Part C up to day 8 post last dose
Immunogenicity, Anti-ONO-4685-antibodies (ADA)	Assessment of antibodies generated to ONO-4685 to measure potential immunogenicity.	Part A up to day 85, Part B and Part C up to day 113
Efficacy, Psoriasis Area and Severity Index (PASI)	Assessment of change in PASI from baseline.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Efficacy, Psoriasis Area and Severity Index (PASI) 50	Assessment of number of subjects that achieve PASI 50, a 50% reduction in PASI from baseline.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Efficacy, Psoriasis Area and Severity Index (PASI) 75	Assessment of number of subjects that achieve PASI 75, a 75% reduction in PASI from baseline.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Efficacy, Psoriasis Area and Severity Index (PASI) 90	Assessment of number of subjects that achieve PASI 90, a 90% reduction in PASI from baseline.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Efficacy, Target Plaque Severity Score (TPSS)	Assessment of change in TPSS from baseline.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Efficacy, Physician's Global Assessment (PGA)	Assessment of change in PGA from baseline.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Efficacy, Physician's Global Assessment (PGA) 0/1	Assessment of the number of subjects that achieve PGA 0/1.	Part A up to day 85, Part B up to day 113, Part C up to day 169
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.	Part A up to day 85, Part B up to day 113, Part C up to day 169
Efficacy, Body Surface Area (BSA)	Assessment of the change in plaque BSA from baseline	Part A up to day 85, Part B up to day 113, Part C up to day 169
Patient Reported Outcome, Dermatology Life Quality Index (DLQI)	Assessment of the change in DLQI from baseline.	Part A up to day 85, Part B up to day 113, Part C up to day 169

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Project Leader, Ono Pharmaceutical Co. Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2022
• Primary Completion (Actual): July 18, 2024
• Study Completion (Actual): July 18, 2024

Study Registration Dates

• First Submitted: March 18, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Psoriasis; PD-1; PD-1 Receptor; ONO-4685; Bi-specific antibody; PD-1 Agonist
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: ONO-4685-02; 2021-002151-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No