Clinical trial NCT03591887: A Study to Evaluate ABY-035 in Subjects With Moderate-to-severe Plaque Psoriasis
Official title: A Phase II, Randomized, Parallel Group, Placebo-controlled, Double-blinded, Dose-finding Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of ABY-035 in Subjects With Moderate-to-severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Plaque Psoriasis
Lead sponsor: Affibody
Sponsor class: INDUSTRY
Collaborators: name: TFS Trial Form Support
First posted: 2018-07-19
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, double-blinded dose-finding study evaluates four dose levels of ABY-035, in comparison to placebo, in subjects with moderate to severe plaque psoriasis.

The study consists of 52-week Core study and two optional 52-week periods, Extension and Prolongation of Extension.

The Core study consists of three periods: Induction (placebo-controlled, Week 0-12), Optimization (Week 12-24), and Individualization (Week 24-52).

Detailed description: The Core study evaluates four doses of ABY-035, in comparison to placebo, in subjects with moderate to severe plaque psoriasis. The treatment periods in the Core study are:

* Induction (Week 0-12) - four dose levels and placebo (Q2W)
* Optimization (Week 12-24) - starting with a possible dose adjustment (all subjects on Q2W) depending on PASI score. Subjects on placebo switch to active drug (Q4W).
* Individualization (Week 24-52) - starting with a switch to Q4W for all subjects. From week 32 dosing interval alters depending on PASI score.

The study is unblinded after completion of the Core study. During the optional Extension and Prolongation of Extension periods, dose levels and intervals alter depending on PASI score.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with plaque psoriasis of at least 6 months prior to Screening, without clinically significant flares during the 12 weeks before randomization, with or without psoriatic arthritis
* Having precedent failure, intolerance and/or contraindication to at least two standard therapies for moderate to-severe plaque psoriasis (systemic therapy and/or phototherapy), and previousinsufficient disease control of topical therapy (e.g. corticosteroids, vitamin D derivatives, cignolin/dithranol).
* Moderate-to-severe plaque psoriasis at Screening and at Baseline as defined by:

  i. Psoriasis involving ≥10% BSA ii. PASI score of ≥ 12 iii. sPGA score of ≥ 3
* Use of highly effective method of contraception or female of non-childbearing potential

Exclusion Criteria:

* Current forms of psoriasis other than chronic plaque-type
* Current drug induced psoriasis
* History of hypersensitivity or allergy to the IMP or its excipients
* History of recurrent or medically important infections requiring intervention and/or systemic treatment in the last 12 months, including infections with e.g. candida and Staphylococcus aureus
* History of or any signs of lymphoproliferative disease, or a known malignancy or a history of malignancy within the previous 5 years (with the exception of basal cell or squamous cell carcinoma of the skin that had been fully excised with no evidence of recurrence)
* Autoimmune disease of relevance
* Inflammatory Bowel Disease requiring treatment within the past 12 months
* Clinically significant heart condition which is not well controlled by current therapy, as assessed by the Investigator
* Significantly immunocompromised subject
* Blood pressure out of range
* Laboratory values out of range, including ALT, AST, eGFR
* Positive to HIV, hepatitis B, hepatitis C or tuberculosis
* Recent previous psoriasis treatments, within defined wash-out periods
* Prior exposure to systemic psoriasis treatments with anti-IL-17 biological therapies
* Live vaccination within defined time restrictions
* Inability or unwillingness to limit ultraviolet (UV) light exposure during the course of the study
* Pregnancy, breast feeding
* Drug and/or alcohol abuse or dependence

Primary outcomes:
measure: Proportion of subjects with a ≥90% improvement in Psoriasis Area and Severity Index (PASI90) at week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of treatment emergent Adverse Events
timeFrame: 52 weeks
measure: Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 24
timeFrame: 24 weeks
measure: Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 52
timeFrame: 52 weeks
measure: Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 12
timeFrame: 12 weeks
measure: Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 24
timeFrame: 24 weeks
measure: Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 52
timeFrame: 52 weeks
measure: Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 12
timeFrame: 12 weeks
measure: Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 24
timeFrame: 24 weeks
measure: Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 52
timeFrame: 52 weeks
measure: Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 12
timeFrame: 12 weeks
measure: Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 24
timeFrame: 24 weeks
measure: Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 52
timeFrame: 52 weeks
measure: Change from baseline in PASI score at week 12
timeFrame: Week 12
measure: Change from baseline in PASI score at week 24
timeFrame: Week 24
measure: Change from baseline in PASI score at week 52
timeFrame: Week 52
measure: Proportion of subjects achieving an absolute PASI score ≤1 at week 12
timeFrame: 12 weeks
measure: Proportion of subjects achieving an absolute PASI score ≤1 at week 24
timeFrame: 24 weeks
measure: Proportion of subjects achieving an absolute PASI score ≤1 at week 52
timeFrame: 52 weeks
measure: Proportion of subjects achieving an absolute PASI score <3 at week 12
timeFrame: 12 weeks
measure: Proportion of subjects achieving an absolute PASI score <3 at week 24
timeFrame: 24 weeks
measure: Proportion of subjects achieving an absolute PASI score <3 at week 52
timeFrame: 52 weeks
measure: Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 12
timeFrame: 12 weeks
measure: Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 24
timeFrame: 24 weeks
measure: Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 52
timeFrame: 52 weeks
measure: Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 12
timeFrame: 12 weeks
measure: Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 24
timeFrame: 24 weeks
measure: Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 52
timeFrame: 52 weeks
measure: Change from baseline in sPGA at week 12
timeFrame: 12 weeks
measure: Change from baseline in sPGA at week 24
timeFrame: 24 weeks
measure: Change from baseline in sPGA at week 52
timeFrame: 52 weeks
measure: Change from baseline in target nail Nail Psoriasis Severity Index (NAPSI) at week 12
timeFrame: Week 12
measure: Change from baseline in target nail NAPSI at week 24
timeFrame: Week 24
measure: Change from baseline in target nail NAPSI at week 52
timeFrame: Week 52
measure: Proportion of subjects achieving Dermatology Life Quality Index (DLQI) of 0 or 1 at week 12
timeFrame: Week 12
measure: Proportion of subjects achieving DLQI of 0 or 1 at week 24
timeFrame: Week 24
measure: Proportion of subjects achieving DLQI of 0 or 1 at week 52
timeFrame: Week 52
measure: Proportion of subjects achieving DLQI of ≤ 5 at Week 12
timeFrame: Week 12
measure: Proportion of subjects achieving DLQI of ≤ 5 at Week 24
timeFrame: Week 24
measure: Proportion of subjects achieving DLQI of ≤ 5 at Week 52
timeFrame: Week 52
measure: Change from baseline in DLQI at week 12
timeFrame: Week 12
measure: DLQI at week 24 compared to baseline
timeFrame: Week 24
measure: DLQI at week 52 compared to baseline
timeFrame: Week 52
measure: Change from baseline in pain-Visual Analogue Scale (VAS) at week 12
timeFrame: Week 12
measure: Pain-VAS score at Week 24 compared to baseline
timeFrame: Week 24
measure: Pain-VAS score at Week 52 compared to baseline
timeFrame: Week 52
measure: Change from baseline in itch-Visual Analogue Scale (VAS) at week 12
timeFrame: Week 12
measure: Itch-VAS at week 24 compared to baseline
timeFrame: Week 24
measure: Itch-VAS at week 52 compared to baseline
timeFrame: Week 52
measure: Pharmacokinetics: Area Under the Curve (AUC) of ABY-035
timeFrame: 52 weeks
measure: Levels of anti-ABY-035 antibodies in serum
timeFrame: 52 weeks
measure: Number of treatment emerging Adverse Events during the Extension period
timeFrame: Week 52 to Week 104
measure: Number of treatment emerging Adverse Events during the Prolongation of Extension period
timeFrame: Week 104 to Week 156
measure: Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 during the Extension period
timeFrame: Week 52 to Week 104
measure: Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 during the Prolongation of Extension period
timeFrame: Week 104 to Week 156
measure: Levels of anti-ABY-035 antibodies in serum during the Extension period
timeFrame: Week 52 to Week 104
measure: Levels of anti-ABY-035 antibodies in serum during the Prolongation of Extension period
timeFrame: Week 104 to Week 156
measure: Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Prolongation of Extension period
timeFrame: Week 156
measure: Change from baseline in PASI score at end of Extension period
timeFrame: Week 104
measure: Change from baseline in PASI score at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving an absolute PASI score ≤1 at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving an absolute PASI score ≤1 at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving an absolute PASI score <3 at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving an absolute PASI score <3 at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving sPGA of 0 or 1 at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving sPGA of 0 or 1 at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Prolongation of Extension period
timeFrame: Week 156
measure: Change from baseline in sPGA at end of Extension period
timeFrame: Week 104
measure: Change from baseline in sPGA at end of Prolongation Extension period
timeFrame: Week 156
measure: Change from baseline in target nail NAPSI at end of Extension period
timeFrame: Week 104
measure: Change from baseline in target nail NAPSI at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving DLQI of 0 or 1 at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving DLQI of 0 or 1 at end of Prolongation of Extension period
timeFrame: Week 156
measure: Proportion of subjects achieving DLQI of ≤ 5 at end of Extension period
timeFrame: Week 104
measure: Proportion of subjects achieving DLQI of ≤ 5 at end of Prolongation of Extension period
timeFrame: Week 156
measure: DLQI at end of Extension period compared to baseline
timeFrame: Week 104
measure: DLQI at end of Prolongation of Extension period compared to baseline
timeFrame: Week 156
measure: Pain-VAS score at end of Extension period compared to baseline
timeFrame: Week 104
measure: Pain-VAS at end of Prolongation of Extension period compared to baseline
timeFrame: Week 156
measure: Itch-VAS at end of Extension period compared to baseline
timeFrame: Week 104
measure: Itch-VAS at end of Prolongation of Extension period compared to baseline
timeFrame: Week 156
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Rothhaar Studien GmbH
city: Berlin
country: Germany
facility: Praxis für Haut- und Geschlechtskrankheiten im Ärztehaus "Rudolf Virchow"
city: Berlin
country: Germany
facility: Hautzentrum Weissensee
city: Berlin
country: Germany
facility: Hautarztzentrum Tegel
city: Bochum
country: Germany
facility: Klinik für Dermatologie, Venerologie und Allergologie der Ruhr-Universität
city: Bochum
country: Germany
facility: Hautarztpraxis im Jahrhunderthaus
city: Bochum
country: Germany
facility: RuhrDerm - Studienzentrum der Gemeinschaftspraxis für Dermatologie, Venerologie, Allergologie, Phlebologie
city: Buxtehude
country: Germany
facility: Elbe Kliniken Buxtehude
city: Darmstadt
country: Germany
facility: Rosenpark Research
city: Düsseldorf
country: Germany
facility: Privatpraxis Dr. Hilton & Partner
city: Friedrichshafen
country: Germany
facility: Derma-Study-Center FN GmbH
city: Hamburg
country: Germany
facility: SCIderm Clinics
city: Kiel
country: Germany
facility: Klinik für Dermatologie, Venerologie und Allergologie
city: Mahlow
country: Germany
facility: Dermatologische Gemeinschaftspraxis
city: Mainz
country: Germany
facility: Clinical research center (CRC) Department of Dermatology
city: Osnabrück
country: Germany
facility: Dres. Unnewehr
city: Selters
country: Germany
facility: CMS³ - Company for Medical Study & Service Selters UG
city: Wuppertal
country: Germany
facility: CentroDerm GmbH
Study officials:
affiliation: Klinik für Dermatologie, Venerologie und Allergologie
name: Sascha Gerdes, Dr. med
role: PRINCIPAL_INVESTIGATOR
References: