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

Phase 2

Completed

• Conditions: Plaque Psoriasis

• Registration Number: NCT03591887
• Lead Sponsor: Affibody

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.

Study Timeline

• Study Start: 2018-03-07
• Study First Submitted: 2018-06-01
• Study First Submitted QC: 2018-07-18
• Study First Posted: 2018-07-19
• Primary Completion: 2019-03-27
• Study Completion: 2021-12-03
• Status Verified: 2023-05
• Last Update Submitted: 2023-06-06
• Last Update Posted: 2023-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 108

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 24	24 weeks	A ≥90% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 52	52 weeks	A ≥90% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 12	12 weeks	A ≥50% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 12	12 weeks	A ≥75% reduction from Baseline in PASI score
Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 24	24 weeks	A 100% reduction from Baseline in PASI score
Proportion of subjects achieving an absolute PASI score ≤1 at week 12	12 weeks	PASI ≤1 equals clear or almost clear skin
Number of treatment emergent Adverse Events	52 weeks	Adverse Events starting after first administration of study drug
Change from baseline in PASI score at week 24	Week 24	PASI: Psoriasis Area and Severity Index
Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 52	52 weeks	A ≥50% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 24	24 weeks	A ≥75% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 52	52 weeks	A ≥75% reduction from Baseline in PASI score
Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 12	12 weeks	A 100% reduction from Baseline in PASI score
Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 52	52 weeks	A 100% reduction from Baseline in PASI score
Change from baseline in PASI score at week 12	Week 12	PASI: Psoriasis Area and Severity Index
Change from baseline in PASI score at week 52	Week 52	PASI: Psoriasis Area and Severity Index
Proportion of subjects achieving an absolute PASI score ≤1 at week 52	52 weeks	PASI ≤1 equals clear or almost clear skin
Proportion of subjects achieving an absolute PASI score <3 at week 24	24 weeks	PASI: Psoriasis Area and Severity Index
Proportion of subjects achieving an absolute PASI score <3 at week 12	12 weeks	PASI: Psoriasis Area and Severity Index
Proportion of subjects achieving an absolute PASI score <3 at week 52	52 weeks	PASI: Psoriasis Area and Severity Index
Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 12	12 weeks	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)
Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 24	24 weeks	sPGA: Static Physician's Global Assessment
Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 52	52 weeks	sPGA: Static Physician's Global Assessment
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 12	12 weeks	sPGA: Static Physician's Global Assessment
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 24	24 weeks	sPGA: Static Physician's Global Assessment
Change from baseline in sPGA at week 24	24 weeks	sPGA: Static Physician's Global Assessment
Change from baseline in sPGA at week 52	52 weeks	sPGA: Static Physician's Global Assessment
Change from baseline in target nail Nail Psoriasis Severity Index (NAPSI) at week 12	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.
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 52	52 weeks	sPGA: Static Physician's Global Assessment
Change from baseline in sPGA at week 12	12 weeks	sPGA: Static Physician's Global Assessment
Change from baseline in target nail NAPSI at week 24	Week 24	NAPSI: Nail Psoriasis Severity Index
Proportion of subjects achieving Dermatology Life Quality Index (DLQI) of 0 or 1 at week 12	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.
Proportion of subjects achieving DLQI of 0 or 1 at week 24	Week 24	DLQI: Dermatology Life Quality Index
Proportion of subjects achieving DLQI of 0 or 1 at week 52	Week 52	DLQI: Dermatology Life Quality Index
Change from baseline in target nail NAPSI at week 52	Week 52	NAPSI: Nail Psoriasis Severity Index
Proportion of subjects achieving DLQI of ≤ 5 at Week 12	Week 12	DLQI: Dermatology Life Quality Index
Proportion of subjects achieving DLQI of ≤ 5 at Week 24	Week 24	DLQI: Dermatology Life Quality Index
Proportion of subjects achieving DLQI of ≤ 5 at Week 52	Week 52	DLQI: Dermatology Life Quality Index
Change from baseline in DLQI at week 12	Week 12	DLQI: Dermatology Life Quality Index
DLQI at week 52 compared to baseline	Week 52	DLQI: Dermatology Life Quality Index
Change from baseline in pain-Visual Analogue Scale (VAS) at week 12	Week 12	Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)
Pain-VAS score at Week 24 compared to baseline	Week 24	Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)
Change from baseline in itch-Visual Analogue Scale (VAS) at week 12	Week 12	Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)
Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 during the Extension period	Week 52 to Week 104	AUC is a measure of the drug exposure
DLQI at week 24 compared to baseline	Week 24	DLQI: Dermatology Life Quality Index
Pain-VAS score at Week 52 compared to baseline	Week 52	Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)
Itch-VAS at week 24 compared to baseline	Week 24	Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)
Number of treatment emerging Adverse Events during the Prolongation of Extension period	Week 104 to Week 156	Adverse Events starting after first administration of study drug
Itch-VAS at week 52 compared to baseline	Week 52	Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)
Levels of anti-ABY-035 antibodies in serum	52 weeks	Anti-drug antibodies
Number of treatment emerging Adverse Events during the Extension period	Week 52 to Week 104	Adverse Events starting after first administration of study drug
Pharmacokinetics: Area Under the Curve (AUC) of ABY-035 during the Prolongation of Extension period	Week 104 to Week 156	AUC is a measure of the drug exposure
Pharmacokinetics: Area Under the Curve (AUC) of ABY-035	52 weeks	AUC is a measure of the drug exposure
Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Prolongation of Extension period	Week 156	A ≥90% reduction from Baseline in PASI score
Levels of anti-ABY-035 antibodies in serum during the Extension period	Week 52 to Week 104	Anti-drug antibodies
Levels of anti-ABY-035 antibodies in serum during the Prolongation of Extension period	Week 104 to Week 156	Anti-drug antibodies
Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at end of Extension period	Week 104	A ≥90% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Extension period	Week 104	A ≥50% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at end of Prolongation of Extension period	Week 156	A ≥50% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Extension period	Week 104	A ≥75% reduction from Baseline in PASI score
Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at end of Prolongation of Extension period	Week 156	A ≥75% reduction from Baseline in PASI score
Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Extension period	Week 104	A 100% reduction from Baseline in PASI score
Proportion of subjects achieving a 100% improvement in PASI (PASI100) at end of Prolongation of Extension period	Week 156	A 100% reduction from Baseline in PASI score
Proportion of subjects achieving an absolute PASI score <3 at end of Extension period	Week 104	PASI: Psoriasis Area and Severity Index
Proportion of subjects achieving an absolute PASI score <3 at end of Prolongation of Extension period	Week 156	PASI: Psoriasis Area and Severity Index
Change from baseline in PASI score at end of Extension period	Week 104	PASI: Psoriasis Area and Severity Index
Change from baseline in PASI score at end of Prolongation of Extension period	Week 156	PASI: Psoriasis Area and Severity Index
Proportion of subjects achieving an absolute PASI score ≤1 at end of Extension period	Week 104	PASI ≤1 equals clear or almost clear skin
Proportion of subjects achieving sPGA of 0 or 1 at end of Prolongation of Extension period	Week 156	sPGA: Static Physician's Global Assessment
Change from baseline in sPGA at end of Extension period	Week 104	sPGA: Static Physician's Global Assessment
Pain-VAS score at end of Extension period compared to baseline	Week 104	Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)
Proportion of subjects achieving an absolute PASI score ≤1 at end of Prolongation of Extension period	Week 156	PASI ≤1 equals clear or almost clear skin
Change from baseline in sPGA at end of Prolongation Extension period	Week 156	sPGA: Static Physician's Global Assessment
Change from baseline in target nail NAPSI at end of Prolongation of Extension period	Week 156	NAPSI: Nail Psoriasis Severity Index
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Extension period	Week 104	sPGA: Static Physician's Global Assessment
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Prolongation of Extension period	Week 156	sPGA: Static Physician's Global Assessment
Change from baseline in target nail NAPSI at end of Extension period	Week 104	NAPSI: Nail Psoriasis Severity Index
Proportion of subjects achieving DLQI of 0 or 1 at end of Extension period	Week 104	DLQI: Dermatology Life Quality Index
Proportion of subjects achieving DLQI of 0 or 1 at end of Prolongation of Extension period	Week 156	DLQI: Dermatology Life Quality Index
Proportion of subjects achieving DLQI of ≤ 5 at end of Extension period	Week 104	DLQI: Dermatology Life Quality Index
Proportion of subjects achieving DLQI of ≤ 5 at end of Prolongation of Extension period	Week 156	DLQI: Dermatology Life Quality Index
Pain-VAS at end of Prolongation of Extension period compared to baseline	Week 156	Pain-VAS: A patient measurement of level pain, from 0 (no pain) to 100 (worst possible pain)
DLQI at end of Prolongation of Extension period compared to baseline	Week 156	DLQI: Dermatology Life Quality Index
Itch-VAS at end of Extension period compared to baseline	Week 104	Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)
Itch-VAS at end of Prolongation of Extension period compared to baseline	Week 156	Itch-VAS: A patient measurement of level itching from 0 (no itch) to 100 (worst possible itch)
DLQI at end of Extension period compared to baseline	Week 104	DLQI: Dermatology Life Quality Index
Proportion of subjects achieving an absolute PASI score ≤1 at week 24	24 weeks	PASI ≤1 equals clear or almost clear skin
Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 24	24 weeks	A ≥50% reduction from Baseline in PASI score
Proportion of subjects achieving sPGA of 0 or 1 at end of Extension period	Week 104	sPGA: Static Physician's Global Assessment

Trial Locations

Locations (18)

Rothhaar Studien GmbH; 🇩🇪 Berlin, Germany

Praxis für Haut- und Geschlechtskrankheiten im Ärztehaus "Rudolf Virchow"; 🇩🇪 Berlin, Germany

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

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