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

NCT05332704 | Completed Phase 1

• 2 other identifiers: ONO-4685-022021-002151-10
• Study Type: interventional
• Target: 33
• Locations: 3 countries
• Sites: 4

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.

Conditions

Plaque Psoriasis

Keywords

Psoriasis; ONO-4685; PD-1; Bi-specific antibody; PD-1 Receptor; PD-1 Agonist

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (24)

• 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.

• Pharmacokinetics, Cmax

  Part A up to day 85, Part B and Part C up to day 113

• Pharmacokinetics, Tmax

  Part A up to day 85, Part B and Part C up to day 113

• Pharmacokinetics, AUC last

  Part A up to day 85

• Pharmacokinetics, AUCinf

  Part A up to day 85

Study Arms (6)

Part A, Active

EXPERIMENTAL

Drug: ONO-4685

Part A, Placebo

PLACEBO COMPARATOR

Drug: Placebo

Part B, Active

EXPERIMENTAL

Drug: ONO-4685

Part B, Placebo

PLACEBO COMPARATOR

Drug: Placebo

Part C, Active

EXPERIMENTAL

Drug: ONO-4685

Part C, Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ONO-4685 DRUG

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

Part A, Active

Placebo DRUG

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

Part A, Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (4)

Arensia Exploratory Medicine Phase 1 Unit

Chisinau, MD-2025, Moldova

Location

Arensia Exploratory Medicine

Bucharest, 011658, Romania

Location

Hammersmith Medicines Research

London, NW10 7EW, United Kingdom

Location

Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Psoriasis

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Project Leader

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study. The pharmacist will be unblinded and is responsible for preparing blinded drug for administration.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 18, 2022
• First Posted: April 18, 2022
• Study Start: March 25, 2022
• Primary Completion: July 18, 2024
• Study Completion: July 18, 2024
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1); MO (1); GB (2)