Multiple Dose Study of UCB4940 in Subjects With Psoriatic Arthritis

A Subject-blind, Investigator-blind, Randomized, Placebo-controlled Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of UCB4940 in Subjects With Psoriatic Arthritis

A study of UCB4940 in subjects with psoriatic arthritis to evaluate the safety and body distribution of UCB4940 in those patients. Neither the patient nor the doctor will know the treatment group.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: UCB4940 160 mg; Drug: UCB4940 240 mg; Other: Placebo; Drug: UCB4940 80 mg; Drug: UCB4940 40 mg; Drug: UCB4940 320 mg; Drug: UCB4940 560 mg

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • 001
• Moldova, Republic of
  • St. Chisinau, Moldova, Republic of
    • 002
• United Kingdom
  • Manchester, United Kingdom
    • 003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a diagnosis of adult-onset psoriatic arthritis made at least 6 months prior to Screening as defined by the Classification Criteria for Psoriatic Arthritis
• Subject must have active psoriatic lesions or a history of psoriatic skin lesions
• Subject must have active arthritis
• Subject has had inadequate response to at least 1 nonbiologic Disease-Modifying Antirheumatic Drug (DMARD) (which may include methotrexate [MTX]) and/or 1 approved biologic DMARD
• Subject must be taking concurrent MTX for at least 3 months at time of Screening, and be on a stable dose at least 4 weeks prior to Baseline
• Female subject must be postmenopausal (at least 1 year), permanently sterilized or, if of childbearing potential, must be willing to use at least 2 effective methods of contraception during the study period
• Subject has clinical laboratory test results within the reference ranges of the testing laboratory
• Subject has Electrocardiogram (ECG) values within the reference ranges of the testing laboratory

Exclusion Criteria:

• Subject has absolute neutrophil count <1.5×109/L, and/or lymphocyte count <1.0×109/L
• Subject has known viral hepatitis, has a positive test for hepatitis B surface antigen or is hepatitis C virus antibody positive
• Subject tests positive to human immunodeficiency virus (HIV)-1/2 antibody
• Subject has a past medical history or family history of primary immunodeficiency
• Subject is splenectomized
• Subject has had a severe infection requiring hospitalization and/or treatment with iv antibiotics in the 6 months before the Screening Visit
• Subject has a history of positive tuberculosis (TB) test or evidence of possible TB or latent TB infection at Screening
• Subject has a high risk of acquiring TB infection
• Subject has a history of alcoholism or drug/chemical abuse
• Subject has an active infection or has had a serious within 6 weeks before the first dose of Investigational Medicinal Product (IMP)
• Subject has renal or liver impairment at the Screening Visit
• Subject has active neoplastic disease or history of neoplastic disease within 5 years of study entry (except for basal or squamous cell carcinoma of the skin or carcinoma in situ which has been definitively treated with standard of care approaches and is considered cured at Screening)
• Subject has any other acute or chronic illness which, in the opinion of the Investigator or Study Physician, could pose a threat or harm to the subject
• Subjects must not have a diagnosis of any other inflammatory arthritis, eg, rheumatoid arthritis, sarcoidosis, or systemic lupus erythematosus
• Subject has a current or past history of gastrointestinal ulceration
• Subjects must not have a noninflammatory condition (eg, osteoarthritis or a known diagnosis of fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of IMP on the subject's primary diagnosis of Psoriatic Arthritis (PsA)
• Subject has received a live vaccination within 6 weeks before the Screening Visit or intends to have or will need a live vaccination during the course of the study or for the 3 months following last IMP dosing
• Subject has had an inadequate response to more than 1 approved biologic Drug-Modifying Antirheumatic Drug (DMARD)
• Subject has received any investigational drug or experimental procedure within 90 days or 5 half-lives whichever is the longer before the first dose of UCB4940

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 240/160/160 mg of UCB4940; 240 mg loading dose + 160 mg maintenance dose every 3 weeks on 2 occasions (total 3 doses)	Drug: UCB4940 160 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Drug: UCB4940 240 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Other: Placebo; Pharmaceutical Form: solution; Concentration: 0.9 % sodium chloride; Route of Administration: intravenous
Experimental: 160/80/80 mg of UCB4940; 160 mg loading dose + 80 mg maintenance dose every 3 weeks on 2 occasions (total 3 doses)	Drug: UCB4940 160 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Other: Placebo; Pharmaceutical Form: solution; Concentration: 0.9 % sodium chloride; Route of Administration: intravenous; Drug: UCB4940 80 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous
Experimental: 80/40/40 mg of UCB4940; 80 mg loading dose + 40 mg maintenance dose every 3 weeks on 2 occasions (total 3 doses)	Other: Placebo; Pharmaceutical Form: solution; Concentration: 0.9 % sodium chloride; Route of Administration: intravenous; Drug: UCB4940 80 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Drug: UCB4940 40 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous
Experimental: 560/320/320 mg of UCB4940; 560 mg loading dose + 320 mg maintenance dose every 3 weeks on 2 occasions (total 3 doses)	Other: Placebo; Pharmaceutical Form: solution; Concentration: 0.9 % sodium chloride; Route of Administration: intravenous; Drug: UCB4940 320 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Drug: UCB4940 560 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous
Placebo Comparator: Placebo; 0.9% sodium chloride aqueous solution (physiological saline, preservative free) of pharmacopoeia (USP/Ph.Eur) quality in a 10 mL glass vial	Drug: UCB4940 160 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Drug: UCB4940 240 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Drug: UCB4940 80 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Drug: UCB4940 40 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Drug: UCB4940 320 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous; Drug: UCB4940 560 mg; Active Substance: UCB4940; Pharmaceutical Form: solution; Concentration: vials at 80 mg/mL will be diluted with 0.9 % sodium chloride to a final concentration calculated to achieve the correct dose; Route of Administration: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration at steady state (CmaxSS) of UCB 4940 during the duration of the study (up to Day 141)	Day 1: predose; 1 hour (hr), 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 8, 15: 1 sample; Day 22: predose, 1 hr postdose; Day 43: predose; 1 hr, 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 48, 57, 64, 85, 141: 1 sample	From Baseline to Day 141
Minimum plasma concentration at steady state (CminSS) of UCB4940 during the duration of the study (up to Day 141)	Day 1: predose; 1 hour (hr), 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 8, 15: 1 sample; Day 22: predose, 1 hr postdose; Day 43: predose; 1 hr, 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 48, 57, 64, 85, 141: 1 sample	From Baseline to Day 141
Area under the curve at steady state (AUCtau) of UCB4940 during the duration of the study (up to Day 141)	Day 1: predose; 1 hour (hr), 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 8, 15: 1 sample; Day 22: predose, 1 hr postdose; Day 43: predose; 1 hr, 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 48, 57, 64, 85, 141: 1 sample	From Baseline to Day 141
Time to reach maximum plasma concentration at steady state (tmax) of UCB4940 during the duration of the study (up to Day 141)	Day 1: predose; 1 hour (hr), 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 8, 15: 1 sample; Day 22: predose, 1 hr postdose; Day 43: predose; 1 hr, 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 48, 57, 64, 85, 141: 1 sample	From Baseline to Day 141
Total Clearance (CL) of UCB4940 during the duration of the study (up to Day 141)	Day 1: predose; 1 hour (hr), 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 8, 15: 1 sample; Day 22: predose, 1 hr postdose; Day 43: predose; 1 hr, 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 48, 57, 64, 85, 141: 1 sample	From Baseline to Day 141
Volume of distribution (V) of UCB4940 during the duration of the study (up to Day 141)	Day 1: predose; 1 hour (hr), 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 8, 15: 1 sample; Day 22: predose, 1 hr postdose; Day 43: predose; 1 hr, 1.5 hr, 5 hr, 12 hr, 24 hr postdose; Day 48, 57, 64, 85, 141: 1 sample	From Baseline to Day 141
Percentage of subjects with at least one Treatment Emergent Adverse Event (TEAE) during the study		From Baseline to Day 141

Collaborators and Investigators

• Sponsor: UCB Celltech
• Collaborators: Parexel; Comac Medical; MAC Clinical Research; ARENSIA, Moldova

Publications and helpful links

General Publications

• Glatt S, Baeten D, Baker T, Griffiths M, Ionescu L, Lawson ADG, Maroof A, Oliver R, Popa S, Strimenopoulou F, Vajjah P, Watling MIL, Yeremenko N, Miossec P, Shaw S. Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis. 2018 Apr;77(4):523-532. doi: 10.1136/annrheumdis-2017-212127. Epub 2017 Dec 23.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: May 15, 2014
• First Submitted That Met QC Criteria: May 15, 2014
• First Posted (Estimate): May 19, 2014

Study Record Updates

• Last Update Posted (Estimate): September 1, 2015
• Last Update Submitted That Met QC Criteria: August 31, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Psoriatic Arthritis
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: PA0007; 2013-004949-16 (EudraCT Number)