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

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

Official Title
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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

Conditions
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Mild to Moderate Psoriasis

Intervention / Treatment
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* Drug: UCB4940
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, UCB4940