A Study to Evaluate ABY-035 in Subjects With Moderate-to-severe Plaque Psoriasis (AFFIRM-35)

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

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).

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Biological: ABY-035; Biological: Placebo

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 Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10783
    • Rothhaar Studien GmbH
  • Berlin, Germany, 13055
    • Praxis für Haut- und Geschlechtskrankheiten im Ärztehaus "Rudolf Virchow"
  • Berlin, Germany, 13086
    • Hautzentrum Weißensee
  • Berlin, Germany, 13507
    • Hautarztzentrum Tegel
  • Bochum, Germany, 44791
    • Klinik für Dermatologie, Venerologie und Allergologie der Ruhr-Universität
  • Bochum, Germany, 44793
    • Hautarztpraxis im Jahrhunderthaus
  • Bochum, Germany, 44803
    • RuhrDerm - Studienzentrum der Gemeinschaftspraxis für Dermatologie, Venerologie, Allergologie, Phlebologie
  • Buxtehude, Germany, 21615
    • Elbe Kliniken Buxtehude
  • Darmstadt, Germany, 64283
    • Rosenpark Research
  • Düsseldorf, Germany, 40212
    • Privatpraxis Dr. Hilton & Partner
  • Friedrichshafen, Germany, 88045
    • Derma-Study-Center Fn Gmbh
  • Hamburg, Germany, 20354
    • SCIderm Clinics
  • Kiel, Germany, 24105
    • Klinik für Dermatologie, Venerologie und Allergologie
  • Mahlow, Germany, 15831
    • Dermatologische Gemeinschaftspraxis
  • Mainz, Germany, 55131
    • Clinical research center (CRC) Department of Dermatology
  • Osnabrück, Germany, 49078
    • Dres. Unnewehr
  • Selters, Germany, 56242
    • CMS³ - Company for Medical Study & Service Selters UG
  • Wuppertal, Germany, 42287
    • CentroDerm GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABY-035 2 mg; 2 mg ABY-035 SC	Biological: ABY-035; ABY-035 solution for injection
Experimental: ABY-035 20 mg; 20 mg ABY-035 SC	Biological: ABY-035; ABY-035 solution for injection
Experimental: ABY-035 80 mg; 80 mg ABY-035 SC	Biological: ABY-035; ABY-035 solution for injection
Experimental: ABY-035 160 mg; 160 mg ABY-035 SC	Biological: ABY-035; ABY-035 solution for injection
Placebo Comparator: Placebo; Placebo, switching to 80 mg ABY-035 after 12 weeks	Biological: Placebo; Placebo to ABY-035 solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 24	A ≥90% reduction from Baseline in PASI score	24 weeks
Proportion of subjects achieving a ≥90% improvement in PASI (PASI90) at week 52	A ≥90% reduction from Baseline in PASI score	52 weeks
Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 12	A ≥75% reduction from Baseline in PASI score	12 weeks
Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 12	A 100% reduction from Baseline in PASI score	12 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.	Week 12
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)	Week 12
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)	Week 12
Number of treatment emergent Adverse Events	Adverse Events starting after first administration of study drug	52 weeks
Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 12	A ≥50% reduction from Baseline in PASI score	12 weeks
Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 24	A ≥50% reduction from Baseline in PASI score	24 weeks
Proportion of subjects achieving a ≥50% improvement in PASI (PASI50) at week 52	A ≥50% reduction from Baseline in PASI score	52 weeks
Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 24	A ≥75% reduction from Baseline in PASI score	24 weeks
Proportion of subjects achieving a ≥75% improvement in PASI (PASI75) at week 52	A ≥75% reduction from Baseline in PASI score	52 weeks
Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 24	A 100% reduction from Baseline in PASI score	24 weeks
Proportion of subjects achieving a 100% improvement in PASI (PASI100) at week 52	A 100% reduction from Baseline in PASI score	52 weeks
Change from baseline in PASI score at week 12	PASI: Psoriasis Area and Severity Index	Week 12
Change from baseline in PASI score at week 24	PASI: Psoriasis Area and Severity Index	Week 24
Change from baseline in PASI score at week 52	PASI: Psoriasis Area and Severity Index	Week 52
Proportion of subjects achieving an absolute PASI score ≤1 at week 12	PASI ≤1 equals clear or almost clear skin	12 weeks
Proportion of subjects achieving an absolute PASI score ≤1 at week 24	PASI ≤1 equals clear or almost clear skin	24 weeks
Proportion of subjects achieving an absolute PASI score ≤1 at week 52	PASI ≤1 equals clear or almost clear skin	52 weeks
Proportion of subjects achieving an absolute PASI score <3 at week 12	PASI: Psoriasis Area and Severity Index	12 weeks
Proportion of subjects achieving an absolute PASI score <3 at week 24	PASI: Psoriasis Area and Severity Index	24 weeks
Proportion of subjects achieving an absolute PASI score <3 at week 52	PASI: Psoriasis Area and Severity Index	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)	12 weeks
Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 24	sPGA: Static Physician's Global Assessment	24 weeks
Proportion of subjects achieving Static Physician's Global Assessment (sPGA) 1 or 0 at week 52	sPGA: Static Physician's Global Assessment	52 weeks
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 12	sPGA: Static Physician's Global Assessment	12 weeks
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 24	sPGA: Static Physician's Global Assessment	24 weeks
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at week 52	sPGA: Static Physician's Global Assessment	52 weeks
Change from baseline in sPGA at week 12	sPGA: Static Physician's Global Assessment	12 weeks
Change from baseline in sPGA at week 24	sPGA: Static Physician's Global Assessment	24 weeks
Change from baseline in sPGA at week 52	sPGA: Static Physician's Global Assessment	52 weeks
Change from baseline in target nail NAPSI at week 24	NAPSI: Nail Psoriasis Severity Index	Week 24
Change from baseline in target nail NAPSI at week 52	NAPSI: Nail Psoriasis Severity Index	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.	Week 12
Proportion of subjects achieving DLQI of 0 or 1 at week 24	DLQI: Dermatology Life Quality Index	Week 24
Proportion of subjects achieving DLQI of 0 or 1 at week 52	DLQI: Dermatology Life Quality Index	Week 52
Proportion of subjects achieving DLQI of ≤ 5 at Week 12	DLQI: Dermatology Life Quality Index	Week 12
Proportion of subjects achieving DLQI of ≤ 5 at Week 24	DLQI: Dermatology Life Quality Index	Week 24
Proportion of subjects achieving DLQI of ≤ 5 at Week 52	DLQI: Dermatology Life Quality Index	Week 52
Change from baseline in DLQI at week 12	DLQI: Dermatology Life Quality Index	Week 12
DLQI at week 24 compared to baseline	DLQI: Dermatology Life Quality Index	Week 24
DLQI at week 52 compared to baseline	DLQI: Dermatology Life Quality Index	Week 52
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)	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)	Week 52
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)	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)	Week 52
Pharmacokinetics: Area Under the Curve (AUC) of ABY-035	AUC is a measure of the drug exposure	52 weeks
Levels of anti-ABY-035 antibodies in serum	Anti-drug antibodies	52 weeks
Number of treatment emerging Adverse Events during the Extension period	Adverse Events starting after first administration of study drug	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	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	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	Week 104 to Week 156
Levels of anti-ABY-035 antibodies in serum during the Extension period	Anti-drug antibodies	Week 52 to Week 104
Levels of anti-ABY-035 antibodies in serum during the Prolongation of Extension period	Anti-drug antibodies	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	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	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	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	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	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	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	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	Week 156
Change from baseline in PASI score at end of Extension period	PASI: Psoriasis Area and Severity Index	Week 104
Change from baseline in PASI score at end of Prolongation of Extension period	PASI: Psoriasis Area and Severity Index	Week 156
Proportion of subjects achieving an absolute PASI score ≤1 at end of Extension period	PASI ≤1 equals clear or almost clear skin	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	Week 156
Proportion of subjects achieving an absolute PASI score <3 at end of Extension period	PASI: Psoriasis Area and Severity Index	Week 104
Proportion of subjects achieving an absolute PASI score <3 at end of Prolongation of Extension period	PASI: Psoriasis Area and Severity Index	Week 156
Proportion of subjects achieving sPGA of 0 or 1 at end of Extension period	sPGA: Static Physician's Global Assessment	Week 104
Proportion of subjects achieving sPGA of 0 or 1 at end of Prolongation of Extension period	sPGA: Static Physician's Global Assessment	Week 156
Proportion of subjects achieving ≥2 point improvement from baseline in sPGA at end of Extension period	sPGA: Static Physician's Global Assessment	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	Week 156
Change from baseline in sPGA at end of Extension period	sPGA: Static Physician's Global Assessment	Week 104
Change from baseline in sPGA at end of Prolongation Extension period	sPGA: Static Physician's Global Assessment	Week 156
Change from baseline in target nail NAPSI at end of Extension period	NAPSI: Nail Psoriasis Severity Index	Week 104
Change from baseline in target nail NAPSI at end of Prolongation of Extension period	NAPSI: Nail Psoriasis Severity Index	Week 156
Proportion of subjects achieving DLQI of 0 or 1 at end of Extension period	DLQI: Dermatology Life Quality Index	Week 104
Proportion of subjects achieving DLQI of 0 or 1 at end of Prolongation of Extension period	DLQI: Dermatology Life Quality Index	Week 156
Proportion of subjects achieving DLQI of ≤ 5 at end of Extension period	DLQI: Dermatology Life Quality Index	Week 104
Proportion of subjects achieving DLQI of ≤ 5 at end of Prolongation of Extension period	DLQI: Dermatology Life Quality Index	Week 156
DLQI at end of Extension period compared to baseline	DLQI: Dermatology Life Quality Index	Week 104
DLQI at end of Prolongation of Extension period compared to baseline	DLQI: Dermatology Life Quality Index	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)	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)	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)	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)	Week 156

Collaborators and Investigators

• Sponsor: Affibody
• Collaborators: TFS Trial Form Support
• Investigators: Principal Investigator: Sascha Gerdes, Dr. med, Klinik für Dermatologie, Venerologie und Allergologie

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2018
• Primary Completion (Actual): March 27, 2019
• Study Completion (Actual): December 3, 2021

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: July 18, 2018
• First Posted (Actual): July 19, 2018

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: ABY-035-002; 2017-001615-36 (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