Clinical trial NCT05332704: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Plaque Psoriasis
Keywords: Psoriasis
ONO-4685
PD-1
Bi-specific antibody
PD-1 Receptor
PD-1 Agonist
Lead sponsor: Ono Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
First posted: 2022-04-18
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Treatment emergent adverse events (TEAEs) by severity
timeFrame: End of Study (3 years)
measure: Clinical laboratory tests
timeFrame: End of Study (3 years)
measure: Cytokines
timeFrame: Up to day 8 post dosing day
measure: Lymphocytes
timeFrame: End of Study (3 years)
measure: Vital signs (blood pressure)
timeFrame: End of Study (3 years)
measure: Vital signs (respiration rate)
timeFrame: End of Study (3 years)
measure: Vital signs (temperature)
timeFrame: End of Study (3 years)
measure: Vital signs (pulse rate)
timeFrame: End of Study (3 years)
measure: ECG parameters
timeFrame: End of Study (3 years)
Secondary outcomes:
measure: Pharmacokinetics (Ceoi)
timeFrame: 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.
measure: Pharmacokinetics, Cmax
timeFrame: Part A up to day 85, Part B and Part C up to day 113
measure: Pharmacokinetics, Tmax
timeFrame: Part A up to day 85, Part B and Part C up to day 113
measure: Pharmacokinetics, AUC last
timeFrame: Part A up to day 85
measure: Pharmacokinetics, AUCinf
timeFrame: Part A up to day 85
measure: Pharmacokinetics, CL (Clearance)
timeFrame: Part A up to day 85
measure: Pharmacokinetics, Vss
timeFrame: Part A up to day 85
measure: Pharmacokinetics, T1/2
timeFrame: 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.
measure: Pharmacokinetics, AUCtau
timeFrame: Part B and C, after first (Day 1) and last (Day 15 or 22) dose
measure: Pharmacokinetics, Ctrough
timeFrame: Part B and C, prior to administration of each dose
measure: Pharmacodynamics, lymphocytes
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Pharmacodynamics, immunoglobulin
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Pharmacodynamics, cytokines
timeFrame: Part A up to day 8, Part B and Part C up to day 8 post last dose
measure: Immunogenicity, Anti-ONO-4685-antibodies (ADA)
timeFrame: Part A up to day 85, Part B and Part C up to day 113
measure: Efficacy, Psoriasis Area and Severity Index (PASI)
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Efficacy, Psoriasis Area and Severity Index (PASI) 50
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Efficacy, Psoriasis Area and Severity Index (PASI) 75
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Efficacy, Psoriasis Area and Severity Index (PASI) 90
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Efficacy, Target Plaque Severity Score (TPSS)
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Efficacy, Physician's Global Assessment (PGA)
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Efficacy, Physician's Global Assessment (PGA) 0/1
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Efficacy, Physician's Global Assessment (PGA) 0/1 and a 2-point improvement
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Efficacy, Body Surface Area (BSA)
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
measure: Patient Reported Outcome, Dermatology Life Quality Index (DLQI)
timeFrame: Part A up to day 85, Part B up to day 113, Part C up to day 169
Other outcomes:
Locations:
city: Chisinau
country: Moldova, Republic of
facility: Arensia Exploratory Medicine Phase 1 Unit
city: Bucharest
country: Romania
facility: Arensia Exploratory Medicine
city: London
country: United Kingdom
facility: Hammersmith Medicines Research
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
affiliation: Ono Pharmaceutical Co. Ltd
name: Project Leader
role: STUDY_DIRECTOR
References: