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

Ono Pharmaceutical Co., Ltd.33 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Plaque Psoriasis

Interventions

-Part A: Single ascending doses of ONO-4685 as a single IV dose (Cohort A1-A5).

PlaceboDRUG

-Part A: Single ascending doses of placebo as a single IV dose (Cohort A1-A5).

ONO-4685DRUG

-Part B: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort B1 and B2)

PlaceboDRUG

-Part B: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort B1 and B2).

ONO-4685DRUG

-Part C: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort C1 and C2).

PlaceboDRUG

-Part C: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort C1 and C2).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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).

Locations (4)

Arensia Exploratory Medicine Phase 1 Unit

Chisinau, Moldova

Arensia Exploratory Medicine

Bucharest, Romania

Hammersmith Medicines Research

London, United Kingdom

Medicines Evaluation Unit

Manchester, United Kingdom

Outcomes

Primary Outcomes

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.

Time frame: End of Study (3 years)

Clinical laboratory tests

Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis).

Time frame: End of Study (3 years)

Cytokines

Number of participants with elevated cytokines.

Time frame: Up to day 8 post dosing day

Lymphocytes

Number of participants with depleted lymphocytes.

Time frame: End of Study (3 years)

Vital signs (blood pressure)

Number of participants with clinically significant changes in vital signs (blood pressure)

Time frame: End of Study (3 years)

Vital signs (respiration rate)

Number of participants with clinically significant changes in vital signs (respiration rate)

Time frame: End of Study (3 years)

Vital signs (temperature)

Number of participants with clinically significant changes in vital signs (temperature)

Time frame: End of Study (3 years)

Vital signs (pulse rate)

Number of participants with clinically significant changes in vital signs (pulse rate)

Time frame: End of Study (3 years)

ECG parameters

Number of participants with ECG abnormalities.

Time frame: End of Study (3 years)

Secondary Outcomes

Pharmacokinetics (Ceoi)

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.

Pharmacokinetics, Cmax

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

Pharmacokinetics, Tmax

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

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.

Time frame: 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.

Time frame: Part A up to day 85

Pharmacokinetics, CL (Clearance)

Assessment of the plasma clearance of ONO-4685.

Time frame: Part A up to day 85

Pharmacokinetics, Vss

Assessment of the volume of distribution at steady state of ONO-4685

Time frame: Part A up to day 85

Pharmacokinetics, T1/2

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.

Data from ClinicalTrials.gov

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Pharmacokinetics, AUCtau

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

Pharmacokinetics, Ctrough

Assessment of the trough concentration of ONO-4685 in plasma.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: Part A up to day 85, Part B up to day 113, Part C up to day 169