Study to Assess the Efficacy and Safety of Orismilast in Psoriasis (IASOS)

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2b Dose-Ranging Study to Evaluate the Efficacy and Safety of Orismilast in Adults With Moderate-to-Severe Plaque-Type Psoriasis

This study investigates 3 different doses of orismilast modified release compared to placebo in adult patients with moderate-to-severe plaque-type psoriasis. The purpose of the study is to assess the effect of orismilast modified release in moderate-to-severe plaque-type psoriasis and assess the safety aspects of these 3 different doses.The patients will receive an oral treatment of either orismilast modified release tablets or placebo tablets 2 times a day for 16 weeks.

Study Overview

• Status: Completed
• Conditions: Skin Diseases; Psoriasis
• Intervention / Treatment: Drug: Placebo; Drug: Orismilast modified release tablets

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bad Bentheim, Germany
    • Fachklinik Bad Bentheim
  • Berlin, Germany
    • ISA - Interdisciplinary Study Association GmbH
  • Darmstadt, Germany
    • Rosenpark Research GmbH
  • Dresden, Germany
    • Hautarztpraxis Dr.Gerlach
  • Friedrichshafen, Germany
    • Derma-Study-Center-Friedrichshafen
  • Hamburg, Germany
    • Klinische Forschung Hamburg GmbH
  • Hamburg, Germany
    • TFS Trial From Support GmbH
  • Kiel, Germany
    • MVZ DermaKiel GmbH
  • Langenau, Germany
    • Studienzentrum Dr.Beate Schwarz
  • Mahlow, Germany
    • Hautarztpraxis Mahlow
  • Muenchen, Germany
    • LMU Muenchen, Klinik und Poliklinik fur Dermatologie und Allergologie
  • Osnabrück, Germany
    • KliFOs - Klinische Forschung Osnabrueck
• Poland
  • Białystok, Poland
    • NZOZ Specjalistyczny Orodek Dermatologiczny DERMAL
  • Chorzów, Poland
    • Specjalistyczna Praktyka Lekarska Gabinet Dermatologiczny dr n.med. Edyta Gebska
  • Iwonicz-Zdrój, Poland
    • Zespol Naukowo - Leczniczy Dermatologiczne Centrum Uzdrowiskowe Iwolang Sp. z o.o.
  • Katowice, Poland
    • Provita Sp. z o.o.
  • Kraków, Poland
    • Centrum Medyczne ALL-MED
  • Malbork, Poland
    • Klinika Badawcza
  • Szczecin, Poland
    • Laser Clinic
  • Szczecin, Poland
    • Twoja Przychodnia - Szczecinskie Centrum Medyczne
  • Tarnów, Poland
    • ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o.
  • Warsaw, Poland
    • High-Med.Przychodnia Specjalistyczna
  • Warsaw, Poland
    • Klinika Ambroziak
  • Wrocław, Poland
    • WroMedica
  • Wrocław, Poland
    • CityClinic Przychodnia Lekarsko-Psychologiczna
  • Wrocław, Poland
    • dermMedica Sp z.o.o
• United Kingdom
  • Manchester, United Kingdom
    • Medicines Evaluation Unit
• United States
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Central Connecticut Dermatology
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • GWU MFA
  • Massachusetts
    • Beverly, Massachusetts, United States, 01915
      • Allcutis Research, Llc
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • Allcutis Research, Llc
  • New York
    • New York, New York, United States, 10075
      • Sadick Research Group LLC
    • New York, New York, United States, 10022
      • Bruce E. Katz, MD
  • Ohio
    • Mayfield Heights, Ohio, United States, 44124
      • Apex Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Capable of giving signed informed consent.
2. Male and female patients ≥18 years of age
3. Body weight of >40 kg
4. Diagnosis of chronic, stable plaque-type psoriasis. If the patient is diagnosed with psoriasis arthritis, the arthritis should be stable.
5. Moderate-to-severe plaque-type psoriasis as defined by Psoriasis Activity and Severity Index (PASI) ≥12, body surface area (BSA) ≥10%, and Investigator Global Assessment (IGA) ≥3.
6. Candidate for systemic antipsoriatic treatment or phototherapy.

Exclusion Criteria:

1. Therapy-resistant psoriasis
2. Unstable psoriasis or psoriatic arthritis with acute deterioration within 4 weeks of the Screening visit.
3. History of allergy or hypersensitivity to any component of the study treatment.
4. Active infection (eg, bacteria, viral, fungal) requiring treatment with systemic antibiotics within 4 weeks of the Screening visit.
5. Malignancy or history of malignancy except for treated (ie, cured) basal cell skin carcinomas.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orismilast modified release tablets 20 mg BID; Oral, twice daily morning and evening for 16 weeks	Drug: Orismilast modified release tablets; Orismilast modified release is a next generation phosphodiesterase-4 (PDE4) inhibitor with high selectivity for the PDE4 subtypes linked to inflammation.; Other Names: UNI50001; LEO32731
Experimental: Orismilast modified release tablets 30 mg BID; Oral, twice daily morning and evening for 16 weeks	Drug: Orismilast modified release tablets; Orismilast modified release is a next generation phosphodiesterase-4 (PDE4) inhibitor with high selectivity for the PDE4 subtypes linked to inflammation.; Other Names: UNI50001; LEO32731
Experimental: Orismilast modified release tablets 40 mg BID; Oral, twice daily morning and evening for 16 weeks	Drug: Orismilast modified release tablets; Orismilast modified release is a next generation phosphodiesterase-4 (PDE4) inhibitor with high selectivity for the PDE4 subtypes linked to inflammation.; Other Names: UNI50001; LEO32731
Placebo Comparator: Placebo tablets BID; Oral, twice daily morning and evening for 16 weeks	Drug: Placebo; Matching placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Psoriasis Activity and Severity Index (PASI) Score at Week 16	The Psoriasis Activity and Severity Index (PASI) is a measure of psoriatic disease severity, taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI.	Baseline and Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved 75% Reduction in PASI (PASI75) Response at Week 16	The PASI is a measure of psoriatic disease severity, taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI. PASI75 is 75% reduction from Baseline in PASI score.	At Week 16
Percentage of Participants Who Achieved a Score of Clear (0) or Almost Clear (1) and an at Least 2-point Improvement in Investigator Global Assessment (IGA) at Week 16	The IGA is a measure used by physicians to determine the patient's overall severity of disease. The static version is used in this trial for measurement at a single point in time as indicated in the schedule of assessments. The investigator will rate the severity of patient's psoriasis on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Week 16
Percentage of Participants Who Achieved a Score of Clear (0) or Almost Clear (1) and an at Least 2-point Improvement in Investigator Global Assessment (IGA) at Weeks 4, 8, 12, and 20	The IGA is a measure used by physicians to determine the patient's overall severity of disease. The static version is used in this trial for measurement at a single point in time as indicated in the schedule of assessments. The investigator will rate the severity of patient's psoriasis on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Weeks 4, 8, 12, and 20
Percentage of Participants Who Achieved 75% Reduction in PASI (PASI75) Response at Weeks 4, 8, 12, and 20	The PASI is a measure of psoriatic disease severity, taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI. PASI75 is 75% reduction from Baseline in PASI score.	At Weeks 4, 8, 12, and 20
Percentage of Participants Who Achieved 50%, 90%, and 100% Reduction in PASI Response at Weeks 4, 8, 12, 16, and 20	The PASI is a measure of psoriatic disease severity, taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI. PASI 50, 90, and 100 is 50%, 90%, and 100% reduction from Baseline in PASI score, respectively.	At Weeks 4, 8, 12, 16, and 20
Percent Change From Baseline in Psoriasis Activity and Severity Index (PASI) Score at Weeks 4, 8, 12, and 20	The Psoriasis Activity and Severity Index (PASI) is a measure of psoriatic disease severity, taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI.	Baseline and Weeks 4, 8, 12, and 20
Percent Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Weeks 16 and 20	The DLQI is a 10-item validated questionnaire completed by the patient used to assess the impact of skin disease on the patient's quality of life (QoL) during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0 to 3 ("not at all," "a little," "a lot," and "very much," respectively), giving a total score ranging from 0 to 30. A high score is indicative of a poor QoL.	Baseline and Weeks 16 and 20
Percent Change From Baseline in Affected Body Surface Area (BSA) at Weeks 4, 8, 12, 16, and 20	The BSA assessment estimates the extent of disease or skin affected by psoriasis and is expressed as a percentage of total body surface. BSA was determined by the Investigator or designee using the patient palm = 1% BSA rule. The patient's palm is measured from the wrist to the proximal interphalangeal and thumb.	Baseline and Weeks 4, 8, 12, 16, and 20
Percent Change From Baseline in Total Score of Psoriasis Symptom Scale (PSS) at Weeks 4, 8, 12, 16, and 20	The PSS is a 4-item patient-completed questionnaire (Rentz 2017). It is patient relevant, its domains are reliable and valid, and it takes few minutes to complete. The PSS assesses severity of pain, itching, redness, and burning during the past 24 hours using a 5-point severity scale from 0 = none to 4 = very severe.	Baseline and Weeks 4, 8, 12, 16, and 20
Percent Change From Baseline in Each Individual Item of Psoriasis Symptom Scale (PSS) at Weeks 4, 8, 12, 16, and 20	The PSS is a 4-item patient-completed questionnaire (Rentz 2017). It is patient relevant, its domains are reliable and valid, and it takes few minutes to complete. The PSS assesses severity of pain, itching, redness, and burning during the past 24 hours using a 5-point severity scale from 0 = none to 4 = very severe.	Baseline and Weeks 4, 8, 12, 16, and 20
Percentage of Participants Who Experienced Psoriasis Rebound by Week 20	The Psoriasis Activity and Severity Index (PASI) is a measure of psoriatic disease severity, taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI.	At Week 20

Collaborators and Investigators

• Sponsor: UNION therapeutics
• Investigators: Study Director: P. A., MD, UNION therapeutics A/S

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2021
• Primary Completion (Actual): November 24, 2022
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: December 30, 2021
• First Submitted That Met QC Criteria: December 30, 2021
• First Posted (Actual): January 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Psoriasis; Orismilast
• Additional Relevant MeSH Terms: Skin Diseases, Papulosquamous; Psoriasis; Skin Diseases
• Other Study ID Numbers: UNI50001-203; 2021-003209-22 (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: Yes
• Studies a U.S. FDA-regulated device product: No