A Study to Evaluate ABY-035 in Subjects With Moderate-to-severe Plaque Psoriasis

Affibody108 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

108

Conditions

Plaque Psoriasis

Interventions

ABY-035BIOLOGICAL

ABY-035 solution for injection

PlaceboBIOLOGICAL

Placebo to ABY-035 solution for injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (18)

Rothhaar Studien GmbH

Berlin, Germany

Praxis für Haut- und Geschlechtskrankheiten im Ärztehaus "Rudolf Virchow"

Berlin, Germany

Outcomes

Primary Outcomes

Proportion of subjects with a ≥90% improvement in Psoriasis Area and Severity Index (PASI90) at week 12

The PASI combines the extent of body surface involvement in the body regions head, trunk, arms, and legs. The percent area of the skin involved is estimated per region (0-100%). The severity is estimated by clinical signs of erythema, induration and scaling, from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Overall scores range from 0 (no psoriasis) to 72 (the most severe disease). PASI90 is a ≥90% reduction from Baseline in PASI score

Time frame: 12 weeks

Secondary Outcomes

Number of treatment emergent Adverse Events

Adverse Events starting after first administration of study drug

Time frame: 52 weeks

Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 24

A ≥90% reduction from Baseline in PASI score

Time frame: 24 weeks

Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 52

A ≥90% reduction from Baseline in PASI score

Time frame: 52 weeks

Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 12

A ≥50% reduction from Baseline in PASI score

Time frame: 12 weeks

Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 24

A ≥50% reduction from Baseline in PASI score

Time frame: 24 weeks

Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 52

Data from ClinicalTrials.gov

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Hautzentrum Weissensee

Berlin, Germany

Hautarztzentrum Tegel

Berlin, Germany

Klinik für Dermatologie, Venerologie und Allergologie der Ruhr-Universität

Bochum, Germany

Hautarztpraxis im Jahrhunderthaus

Bochum, Germany

RuhrDerm - Studienzentrum der Gemeinschaftspraxis für Dermatologie, Venerologie, Allergologie, Phlebologie

Bochum, Germany

Elbe Kliniken Buxtehude

Buxtehude, Germany

Rosenpark Research

Darmstadt, Germany

Privatpraxis Dr. Hilton & Partner

Düsseldorf, Germany

...and 8 more locations

A ≥50% reduction from Baseline in PASI score

Time frame: 52 weeks

Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 12

A ≥75% reduction from Baseline in PASI score

Time frame: 12 weeks

Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 24

A ≥75% reduction from Baseline in PASI score

Time frame: 24 weeks

Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 52

A ≥75% reduction from Baseline in PASI score

Time frame: 52 weeks

Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 12

A 100% reduction from Baseline in PASI score

Time frame: 12 weeks

Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 24

A 100% reduction from Baseline in PASI score

Time frame: 24 weeks

Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 52

A 100% reduction from Baseline in PASI score

Time frame: 52 weeks

Change from baseline in PASI score at week 12

PASI: Psoriasis Area and Severity Index

Time frame: Week 12

Change from baseline in PASI score at week 24

PASI: Psoriasis Area and Severity Index

Time frame: Week 24

Change from baseline in PASI score at week 52

PASI: Psoriasis Area and Severity Index

Time frame: Week 52

Proportion of subjects achieving an absolute PASI score ≤1 at week 12

PASI ≤1 equals clear or almost clear skin

Time frame: 12 weeks

Proportion of subjects achieving an absolute PASI score ≤1 at week 24

PASI ≤1 equals clear or almost clear skin

Time frame: 24 weeks

Proportion of subjects achieving an absolute PASI score ≤1 at week 52

PASI ≤1 equals clear or almost clear skin

Time frame: 52 weeks

Proportion of subjects achieving an absolute PASI score <3 at week 12

PASI: Psoriasis Area and Severity Index

Time frame: 12 weeks

Proportion of subjects achieving an absolute PASI score <3 at week 24

PASI: Psoriasis Area and Severity Index

Time frame: 24 weeks

Proportion of subjects achieving an absolute PASI score <3 at week 52

PASI: Psoriasis Area and Severity Index

Time frame: 52 weeks

Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 12

The sPGA is the physician's determination of the subject's Psoriasis lesions overall at a given time point, with the grading 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe)

Time frame: 12 weeks

Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 24

sPGA: Static Physician's Global Assessment

Time frame: 24 weeks

Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 52

sPGA: Static Physician's Global Assessment

Time frame: 52 weeks

Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 12

sPGA: Static Physician's Global Assessment

Time frame: 12 weeks

Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 24

sPGA: Static Physician's Global Assessment

Time frame: 24 weeks

Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 52

sPGA: Static Physician's Global Assessment

Time frame: 52 weeks

Change from baseline in sPGA at week 12

sPGA: Static Physician's Global Assessment

Time frame: 12 weeks

Change from baseline in sPGA at week 24

sPGA: Static Physician's Global Assessment

Time frame: 24 weeks

Change from baseline in sPGA at week 52

sPGA: Static Physician's Global Assessment

Time frame: 52 weeks

Change from baseline in target nail Nail Psoriasis Severity Index (NAPSI) at week 12

The NAPSI scale is used to evaluate the severity of psoriasis in the fingernail bed and matrix. The nail is divided into quadrants. Each quadrant is given the score 0 (absence) or 1 (presence) for psoriasis in the beds and matrix, respectively. The NAPSI score of a nail is the sum of each quadrant. The maximum score per nail is 8. In the target nail NAPSI, the worst affected nail at Baseline is evaluated throughout the study.

Time frame: Week 12

Change from baseline in target nail NAPSI at week 24

NAPSI: Nail Psoriasis Severity Index

Time frame: Week 24

Change from baseline in target nail NAPSI at week 52

NAPSI: Nail Psoriasis Severity Index

Time frame: Week 52

Proportion of subjects achieving Dermatology Life Quality Index (DLQI) of 0 or 1 at week 12

DLQI is a 10-question quality-of-life questionnaire completed by the subject. It covers 6 the domains symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The total scores range from 0 to 30, with higher score indicating greater quality of life impairment.

Time frame: Week 12

Proportion of subjects achieving DLQI of 0 or 1 at week 24

DLQI: Dermatology Life Quality Index

Time frame: Week 24

Proportion of subjects achieving DLQI of 0 or 1 at week 52

DLQI: Dermatology Life Quality Index

Time frame: Week 52

Proportion of subjects achieving DLQI of ≤ 5 at Week 12

DLQI: Dermatology Life Quality Index

Time frame: Week 12

Proportion of subjects achieving DLQI of ≤ 5 at Week 24

DLQI: Dermatology Life Quality Index

Time frame: Week 24

Proportion of subjects achieving DLQI of ≤ 5 at Week 52

DLQI: Dermatology Life Quality Index

Time frame: Week 52

Change from baseline in DLQI at week 12

DLQI: Dermatology Life Quality Index

Time frame: Week 12

DLQI at week 24 compared to baseline

DLQI: Dermatology Life Quality Index

Time frame: Week 24

DLQI at week 52 compared to baseline

DLQI: Dermatology Life Quality Index

Time frame: Week 52

Change from baseline in pain-Visual Analogue Scale (VAS) at week 12

Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)

Time frame: Week 12

Pain-VAS score at Week 24 compared to baseline

Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)

Time frame: Week 24

Pain-VAS score at Week 52 compared to baseline

Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)

Time frame: Week 52

Change from baseline in itch-Visual Analogue Scale (VAS) at week 12

Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)

Time frame: Week 12

Itch-VAS at week 24 compared to baseline

Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)

Time frame: Week 24

Itch-VAS at week 52 compared to baseline

Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)

Time frame: Week 52

Pharmacokinetics: Area Under the Curve (AUC) of ABY-035

AUC is a measure of the drug exposure

Time frame: 52 weeks

Levels of anti-ABY-035 antibodies in serum

Anti-drug antibodies

Time frame: 52 weeks

Number of treatment emerging Adverse Events during the Extension period

Adverse Events starting after first administration of study drug

Time frame: Week 52 to Week 104

Number of treatment emerging Adverse Events during the Prolongation of Extension period

Adverse Events starting after first administration of study drug

Time frame: Week 104 to Week 156

Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 during the Extension period

AUC is a measure of the drug exposure

Time frame: Week 52 to Week 104

Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 during the Prolongation of Extension period

AUC is a measure of the drug exposure

Time frame: Week 104 to Week 156

Levels of anti-ABY-035 antibodies in serum during the Extension period

Anti-drug antibodies

Time frame: Week 52 to Week 104

Levels of anti-ABY-035 antibodies in serum during the Prolongation of Extension period

Anti-drug antibodies

Time frame: Week 104 to Week 156

Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Extension period

A ≥90% reduction from Baseline in PASI score

Time frame: Week 104

Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Prolongation of Extension period

A ≥90% reduction from Baseline in PASI score

Time frame: Week 156

Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Extension period

A ≥50% reduction from Baseline in PASI score

Time frame: Week 104

Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Prolongation of Extension period

A ≥50% reduction from Baseline in PASI score

Time frame: Week 156

Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Extension period

A ≥75% reduction from Baseline in PASI score

Time frame: Week 104

Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Prolongation of Extension period

A ≥75% reduction from Baseline in PASI score

Time frame: Week 156

Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Extension period

A 100% reduction from Baseline in PASI score

Time frame: Week 104

Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Prolongation of Extension period

A 100% reduction from Baseline in PASI score

Time frame: Week 156

Change from baseline in PASI score at end of Extension period

PASI: Psoriasis Area and Severity Index

Time frame: Week 104

Change from baseline in PASI score at end of Prolongation of Extension period

PASI: Psoriasis Area and Severity Index

Time frame: Week 156

Proportion of subjects achieving an absolute PASI score ≤1 at end of Extension period

PASI ≤1 equals clear or almost clear skin

Time frame: Week 104

Proportion of subjects achieving an absolute PASI score ≤1 at end of Prolongation of Extension period

PASI ≤1 equals clear or almost clear skin

Time frame: Week 156

Proportion of subjects achieving an absolute PASI score <3 at end of Extension period

PASI: Psoriasis Area and Severity Index

Time frame: Week 104

Proportion of subjects achieving an absolute PASI score <3 at end of Prolongation of Extension period

PASI: Psoriasis Area and Severity Index

Time frame: Week 156

Proportion of subjects achieving sPGA of 0 or 1 at end of Extension period

sPGA: Static Physician's Global Assessment

Time frame: Week 104

Proportion of subjects achieving sPGA of 0 or 1 at end of Prolongation of Extension period

sPGA: Static Physician's Global Assessment

Time frame: Week 156

Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Extension period

sPGA: Static Physician's Global Assessment

Time frame: Week 104

Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Prolongation of Extension period

sPGA: Static Physician's Global Assessment

Time frame: Week 156

Change from baseline in sPGA at end of Extension period

sPGA: Static Physician's Global Assessment

Time frame: Week 104

Change from baseline in sPGA at end of Prolongation Extension period

sPGA: Static Physician's Global Assessment

Time frame: Week 156

Change from baseline in target nail NAPSI at end of Extension period

NAPSI: Nail Psoriasis Severity Index

Time frame: Week 104

Change from baseline in target nail NAPSI at end of Prolongation of Extension period

NAPSI: Nail Psoriasis Severity Index

Time frame: Week 156

Proportion of subjects achieving DLQI of 0 or 1 at end of Extension period

DLQI: Dermatology Life Quality Index

Time frame: Week 104

Proportion of subjects achieving DLQI of 0 or 1 at end of Prolongation of Extension period

DLQI: Dermatology Life Quality Index

Time frame: Week 156

Proportion of subjects achieving DLQI of ≤ 5 at end of Extension period

DLQI: Dermatology Life Quality Index

Time frame: Week 104

Proportion of subjects achieving DLQI of ≤ 5 at end of Prolongation of Extension period

DLQI: Dermatology Life Quality Index

Time frame: Week 156

DLQI at end of Extension period compared to baseline

DLQI: Dermatology Life Quality Index

Time frame: Week 104

DLQI at end of Prolongation of Extension period compared to baseline

DLQI: Dermatology Life Quality Index

Time frame: Week 156

Pain-VAS score at end of Extension period compared to baseline

Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)

Time frame: Week 104

Pain-VAS at end of Prolongation of Extension period compared to baseline

Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)

Time frame: Week 156

Itch-VAS at end of Extension period compared to baseline

Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)

Time frame: Week 104

Itch-VAS at end of Prolongation of Extension period compared to baseline

Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)

Time frame: Week 156