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

Plaque Psoriasis Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05332704
• Other study ID #: ONO-4685-02
• Secondary ID: 2021-002151-10
• Status: Suspended
• Phase: Phase 1
• Start date: March 25, 2022
• Est. completion date: December 18, 2025

Study information

• Verified date: May 2024
• Source: Ono Pharmaceutical Co. Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 74
• Est. completion date: December 18, 2025
• Est. primary completion date: October 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Plaque Psoriasis
• Psoriasis

Intervention

Drug:
• ONO-4685
-Part A: Single ascending doses of ONO-4685 as a single IV dose (Cohort A1-A5).
• Placebo
-Part A: Single ascending doses of placebo as a single IV dose (Cohort A1-A5).
• ONO-4685
-Part B: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort B1 and B2)
• Placebo
-Part B: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort B1 and B2).
• ONO-4685
-Part C: Multiple doses of ONO-4685 as IV doses over a 4-week treatment period (Cohort C1 and C2).
• Placebo
-Part C: Multiple doses of placebo as IV doses over a 4-week treatment period (Cohort C1 and C2).

Locations

Country	Name	City	State
Moldova, Republic of	Arensia Exploratory Medicine Phase 1 Unit	Chisinau
Romania	Arensia Exploratory Medicine	Bucharest
United Kingdom	Hammersmith Medicines Research	London
United Kingdom	Medicines Evaluation Unit	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

Moldova, Republic of,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Clinical laboratory tests	Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis).	End of Study (3 years)
Primary	Cytokines	Number of participants with elevated cytokines.	Up to day 8 post dosing day
Primary	Lymphocytes	Number of participants with depleted lymphocytes.	End of Study (3 years)
Primary	Vital signs (blood pressure)	Number of participants with clinically significant changes in vital signs (blood pressure)	End of Study (3 years)
Primary	Vital signs (respiration rate)	Number of participants with clinically significant changes in vital signs (respiration rate)	End of Study (3 years)
Primary	Vital signs (temperature)	Number of participants with clinically significant changes in vital signs (temperature)	End of Study (3 years)
Primary	Vital signs (pulse rate)	Number of participants with clinically significant changes in vital signs (pulse rate)	End of Study (3 years)
Primary	ECG parameters	Number of participants with ECG abnormalities.	End of Study (3 years)
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pharmacokinetics, CL (Clearance)	Assessment of the plasma clearance of ONO-4685.	Part A up to day 85
Secondary	Pharmacokinetics, Vss	Assessment of the volume of distribution at steady state of ONO-4685	Part A up to day 85
Secondary	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.
Secondary	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
Secondary	Pharmacokinetics, Ctrough	Assessment of the trough concentration of ONO-4685 in plasma.	Part B and C, prior to administration of each dose
Secondary	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
Secondary	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
Secondary	Pharmacodynamics, cytokines	Assessment of cytokines, including IL-2, IL-6, IL-10, TNF-a and INF-?.	Part A up to day 8, Part B and Part C up to day 8 post last dose
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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