A Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of UCB4940 in Patients With Psoriasis

A Randomized, Subject-blind, Investigator-blind, Placebo-controlled, Single-dose, Dose-escalating Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of UCB4940 in Patients With Mild to Moderate Psoriasis

To evaluate the safety of UCB4940 administered by iv infusion of a single ascending dose in subjects with mild to moderate plaque psoriasis.

Study Overview

• Status: Completed
• Conditions: Mild to Moderate Psoriasis
• Intervention / Treatment: Drug: UCB4940; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom
    • 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subject is male or female, aged ≥ 18 years to ≤ 70 years at Screening. Female subjects must either 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, including a barrier method during the study period. Effective methods of contraception are methods of birth control, which result in a low failure rate when used consistently and correctly, such as implants, injectables, oral contraceptives, progesterone-releasing intrauterine systems or the TCu 380A intrauterine device, complete sexual abstinence, or vasectomized partner. Male subjects with partners of childbearing potential must be willing to use a condom when sexually active. Both male and female subjects must use the above mentioned contraception for 20 weeks after administration of study drug (anticipated 5 half-lives)
• Subject has had a confirmed diagnosis of mild to moderate plaque-type psoriasis for at least 6 months involving ≤ 5 % of body surface area (BSA) (excluding the scalp)
• Subject has a body mass index of ≤ 35 kg/m^2 at Screening
• Subject has a minimum of 2 psoriatic lesions with at least 1 plaque in a site suitable for biopsy

Exclusion Criteria:

• Female subject who is pregnant, or plans to become pregnant during the study, or lactating, or sexually active with childbearing potential who is not using a medically accepted birth control method
• Subject has received systemic nonbiologic psoriasis therapy (methotrexate [MTX], steroids, cyclophosphamide) or psoralen plus ultraviolet A (PUVA)/ultraviolet A (UVA) phototherapy within 4 weeks prior to Screening
• Subject has received treatment with biologic agents within 12 months prior to the study
• Subject has received live attenuated vaccination within 6 weeks prior to Screening or intends to have such a vaccination during the course of the study
• Subject has received any investigational drug or experimental procedure within 90 days or 5 half-lives, whichever is longer, prior to IMP administration
• Subject requires treatment with a nonsteroidal anti-inflammatory drug during the study period. Paracetamol will be permitted for use as an antipyretic and/or analgesic
• Subject has an active infection (eg, sepsis, pneumonia, abscess) or has had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to IMP administration. When in doubt, the Investigator should confer with the UCB Study Physician
• Subject has a history of a positive tuberculosis (TB) test or evidence of possible TB or latent TB infection at Screening that cannot be attributed to a prior Bacillus Calmette-Guérin inoculation

• Subject has renal or liver impairment, defined as:

  • For women, serum creatinine level ≥ 125 μmol/L; for men, ≥ 135 μmol/L, or
  • ALT and aspartate aminotransferase ≥ 2x ULN, or
  • Alkaline phosphatase and bilirubin > 1.5x ULN (an isolated bilirubin > 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin is < 35 %)
• Subject has active neoplastic disease or history of neoplastic disease within 5 years of Screening (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitively treated with standard of care)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UCB4940 8 mg; Single intravenous (iv) infusion of UCB4940 8 mg over at least 60 minutes.	Drug: UCB4940; Active Substance: UCB4940; Pharmaceutical Form: Solution for infusion; Concentration: 80 mg/ml; Route of Administration: Intravenous use
Experimental: UCB4940 40 mg; Single intravenous (iv) infusion of UCB4940 40 mg over at least 60 minutes.	Drug: UCB4940; Active Substance: UCB4940; Pharmaceutical Form: Solution for infusion; Concentration: 80 mg/ml; Route of Administration: Intravenous use
Experimental: UCB4940 160 mg; Single intravenous (iv) infusion of UCB4940 160 mg over at least 60 minutes.	Drug: UCB4940; Active Substance: UCB4940; Pharmaceutical Form: Solution for infusion; Concentration: 80 mg/ml; Route of Administration: Intravenous use
Experimental: UCB4940 480 mg; Single intravenous (iv) infusion of UCB4940 480 mg over at least 60 minutes.	Drug: UCB4940; Active Substance: UCB4940; Pharmaceutical Form: Solution for infusion; Concentration: 80 mg/ml; Route of Administration: Intravenous use
Experimental: UCB4940 640 mg; Single intravenous (iv) infusion of UCB4940 640 mg over at least 60 minutes.	Drug: UCB4940; Active Substance: UCB4940; Pharmaceutical Form: Solution for infusion; Concentration: 80 mg/ml; Route of Administration: Intravenous use
Placebo Comparator: Placebo; Single intravenous (iv) infusion of Placebo over at least 60 minutes.	Other: Placebo; Active Substance: Placebo; Pharmaceutical Form: Solution for infusion; Concentration: 0.9 % sodium chloride aqueous solution; Route of Administration: Intravenous use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects reporting at least 1 Treatment-Emergent Adverse Event (TEAE) during the Treatment Period (20 Weeks)	Baseline to 20 Weeks
Number of subjects prematurely discontinuing due to a Treatment-Emergent Adverse Event (TEAE) during the Treatment Period (20 Weeks)	Baseline to 20 Weeks
Number of subjects reporting at least 1 Serious Adverse Event (SAE) during the Treatment Period (20 Weeks)	Baseline to 20 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration (Cmax)	Pharmacokinetic samples will be taken predose and 0-48 hr post-dose, 72 hr post-dose, 96 hr post-dose, Week-1 through Week-20
Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-inf))	Pharmacokinetic samples will be taken predose and 0-48 hr post-dose, 72 hr post-dose, 96 hr post-dose, Week-1 through Week-20
Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration (AUC(0-t))	Pharmacokinetic samples will be taken predose and 0-48 hr post-dose, 72 hr post-dose, 96 hr post-dose, Week-1 through Week-20
Time to reach Cmax (Tmax)	Pharmacokinetic samples will be taken predose and 0-48 hr post-dose, 72 hr post-dose, 96 hr post-dose, Week-1 through Week-20
Terminal elimination half-life (t1/2)	Pharmacokinetic samples will be taken predose and 0-48 hr post-dose, 72 hr post-dose, 96 hr post-dose, Week-1 through Week-20
First order terminal elimination rate constant (λz)	Pharmacokinetic samples will be taken predose and 0-48 hr post-dose, 72 hr post-dose, 96 hr post-dose, Week-1 through Week-20
Total body clearance (CL)	Pharmacokinetic samples will be taken predose and 0-48 hr post-dose, 72 hr post-dose, 96 hr post-dose, Week-1 through Week-20
Volume of distribution in terminal phase (Vz)	Pharmacokinetic samples will be taken predose and 0-48 hr post-dose, 72 hr post-dose, 96 hr post-dose, Week-1 through Week-20
Percentage Change from Baseline to Week 12 in the Lesion Severity Score (LSS)	Baseline to Week 12
Percentage Change from Baseline to Week 12 in thickness of the plaque	Baseline to Week 12
Percentage Change from Baseline to Week 12 in lesion area	Baseline to Week 12
Percentage Change from Baseline to Week 12 in Psoriasis Area and Severity Index (PASI)	Baseline to Week 12
Percentage Change from Baseline to Week 12 in Physician's Global Assessment (PGA)	Baseline to Week 12

Collaborators and Investigators

• Sponsor: UCB Celltech
• Investigators: Study Director: UCB Clinical Trial Call Center, +1 877 8229493 (UCB)

Publications and helpful links

General Publications

• Glatt S, Helmer E, Haier B, Strimenopoulou F, Price G, Vajjah P, Harari OA, Lambert J, Shaw S. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017 May;83(5):991-1001. doi: 10.1111/bcp.13185. Epub 2017 Jan 10.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: August 19, 2015
• First Submitted That Met QC Criteria: August 19, 2015
• First Posted (Estimate): August 20, 2015

Study Record Updates

• Last Update Posted (Estimate): August 20, 2015
• Last Update Submitted That Met QC Criteria: August 19, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Psoriasis; UCB4940
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: UP0008; 2012-002086-35 (EudraCT Number)