Study to Determine if AZD0284 is Effective and Safe in Treating Plaque Psoriasis (DERMIS)

A Randomized, Double-Blind, Placebo-Controlled, Phase 1b Study to Assess Efficacy and Safety of One Dose Level of Oral AZD0284 Given for Four Weeks, Compared to Placebo, in Patients With Moderate to Severe Plaque Psoriasis

The Sponsor is developing the study drug, AZD0284, for the potential treatment of Plaque psoriasis. Psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery scales. The severity of the disease varies, but in many cases it can have a major impact on their quality of life if not adequately treated.

The purpose of the study is to determine the short term safety, pharmacodynamic and clinical effect of AZD0284 in patients with psoriasis.

Study Overview

• Status: Terminated
• Conditions: Plaque Psoriasis Vulgaris
• Intervention / Treatment: Drug: Placebo; Drug: AZD0284 oral solution 2.5 mg/mL

Detailed Description

This is a randomised, double-blind, placebo-controlled, multi-centre, parallel group Phase 1b study, designed to evaluate the pharmacodynamic effects, clinical efficacy and safety of AZD0284 compared with placebo as measured by the relative change from baseline in Psoriasis Area Severity Index (PASI score), other disease assessments of involved body surface area (BSA), static physicians global assessment score (sPGA), pruritis and biomarkers associated with the mechanism of disease and AZD0284. Disease activity will be assessed throughout the study as will changes in skin biopsy biomarkers. The study population will be comprised of patients with moderate to severe plaque psoriasis as defined by PASI score, BSA and sPGA.

Following completion of screening assessments and meeting all eligibility criteria, patients will be randomised to receive AZD0284 or placebo for 4 weeks of treatment followed by a 4 week follow up period

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aarhus C, Denmark, 8000
    • Research Site
  • Hellerup, Denmark, 2900
    • Research Site
  • Koebenhavn, Denmark, 2400
    • Research Site
  • Odense, Denmark, 5000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed informed consent prior to any study specific procedures.
• At least 6 months documented history with a diagnosis of moderate to severe plaque psoriasis as defined by the Psoriasis Area and Severity Index (PASI), psoriasis Body Surface Area (BSA) and static Physician Global Assessment (sPGA).

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study.
• History and/or presence of tuberculosis, hepatitis, HIV. Other opportunistic infections within 6 months of the study.
• Clinically significant laboratory abnormalities.
• Clinically important abnormalities in rhythm, conduction or morphology of the digital Electrocardiogram (ECG) as considered by the Investigator may interfere with the interpretation of study data.
• Current treatment or treatment for psoriasis with biological therapies within 6 months of study.
• Efficacy and safety failure of biologic therapies targeting the IL-17 and IL12/23 pathway at any time.
• Current treatment or history of treatment for psoriasis with non-biological systemic medications within 4 weeks of Day 1

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo for AZD0284 oral solution	Drug: Placebo; Placebo for AZD0284 oral solution, twice daily for 4 weeks
Experimental: AZD0284; AZD0284 oral solution 2.5 mg/mL	Drug: AZD0284 oral solution 2.5 mg/mL; AZD0284 oral solution 2.5 mg/mL, 100 mg twice daily for for 4 weeks; Other Names: AZD0284

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction from baseline to the end of treatment, in gene expression level of IL-17A and CCL20 relative to placebo.	Reduction from baseline to the end of treatment, in gene expression level of IL-17A and CCL20 relative to placebo.	4 weeks
Percent improvement from baseline to the end of treatment in individual Psoriasis Area and Severity Index (PASI) compared to placebo	Change (percent improvement) in Psoriasis Area and Severity Index score(PASI) compared to placebo	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving 75 % reduction from baseline in PASI score, i.e. PASI 75, at week 4	Percent patients acheiving a 75% reduction in PASI score	4 weeks
Proportion of patients achieving 50 % reduction from baseline in PASI score, i.e. PASI 50, at week 4	Percent patients acheiving a 50% reduction in PASI score	4 weeks
Reduction in static physician's global assessment (sPGA) score from baseline at week4	The change in the Static physician's global assessment (sPGA) score will be assessed	4 weeks
Percent improvement from baseline in involved body surface area (BSA) at week 4	The percent change in the involved body surface area (BSA) will be assessed	4 weeks
Reduction in the pruritus visual analogue scale (pVAS) score from baseline, at week 4	The reduction in the pruritus visual analogue scale (pVAS) score as determined by the patient will be assessed	4 weeks
Cmax : maximum observed plasma concentration	Maximum observed plasma concentration (Cmax) will be assessed	4 weeks
tmax time to reach Cmax	The time to reach the maximum observed plasma concentration (Cmax) will be assessed	4 weeks
Cmin minimum observed plasma concentration	The minimum observed plasma concentration (Cmin) will be assessed	4 weeks
AE(s) and SAE(s)	Safety evaluation will include the assessment of adverse and serious adverse events over the course of the study	Approximately 8 weeks throughout the study

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Ioannis Psallidas, Phd, AstraZeneca R&D, Gothenburg, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2017
• Primary Completion (Actual): April 18, 2018
• Study Completion (Actual): April 18, 2018

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 11, 2017
• First Posted (Actual): October 16, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: PASI; PK; sPGA; Plaque psoriasis; BSA; P-VAS; IL17A-; CCL20
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: D7800C00003; 2017-002351-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No