NCT03051217

A Study to Test the Efficacy and Safety of Certolizumab Pegol in Japanese Subjects With Moderate to Severe Chronic Psoriasis

Completed Phase 2, PHASE3 Results posted Last updated 4 January 2022

What this trial tests

Phase 2, PHASE3 trial testing Placebo in Moderate to Severe Psoriasis in 127 participants. Completed in 16 January 2019.

Timeline

21 February 2017

Primary endpoint
19 November 2018

16 January 2019

Quick facts

Lead sponsor	UCB Biopharma S.P.R.L.
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	127
Start date	21 February 2017
Primary completion	19 November 2018
Estimated completion	16 January 2019
Sites	33 locations across Japan

Drugs / interventions tested

• Placebo
• Certolizumab Pegol (CERTOLIZUMAB PEGOL) — full drug profile →

Conditions studied

• Moderate to Severe Psoriasis — all drugs for Moderate to Severe Psoriasis →
• Generalized Pustular Psoriasis and Erythrodermic Psoriasis — all drugs for Generalized Pustular Psoriasis and Erythrodermic Psoriasis →

Sponsor

UCB Biopharma S.P.R.L. — full company profile →

Who can join

20 and older, any sex, with Moderate to Severe Psoriasis or Generalized Pustular Psoriasis and Erythrodermic Psoriasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Subjects Achieving a 75 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 Primary · Week 16

The PASI75 response assessments were based on at least 75 % improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and

Group	Value	95% CI
Placebo (FAS)	7.9
CZP 200 mg Q2W (FAS)	73.0
CZP 400 mg Q2W (FAS)	87.1

Percentage of Subjects Who Achieve a Physician's Global Assessment (PGA) Clear or Almost Clear Response (With at Least 2-category Improvement) at Week 16 Secondary · Week 16

This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Investigator assessed the overall severity of Psoriasis (PSO) using the following 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe.

Group	Value	95% CI
Placebo (FAS)	0.0
CZP 200 mg Q2W (FAS)	52.7
CZP 400 mg Q2W (FAS)	66.7

Percentage of Subjects Achieving a 90 % or Higher Improvement in Psoriasis Area and Severity Index (PASI) Score at Week 16 Secondary · Week 16

The PASI90 response assessments were based on at least 90 % improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and

Group	Value	95% CI
Placebo (FAS)	0.2
CZP 200 mg Q2W (FAS)	53.8
CZP 400 mg Q2W (FAS)	75.7

Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 Secondary · Baseline and Week 16

This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The DLQI is a subject-reported questionnaire designed for use in adult participants with PSO. The DLQI is a skin disease-specific questionnaire aimed at the evaluation of how symptoms and treatment affect patients' health related quality of life (HRQoL). This instrument asked participants about symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. It has been shown to be valid and reproducible in PSO patients. The DLQI score ranges from 0 to

Group	Value	95% CI
Placebo (FAS)	-0.3	± 1.0
CZP 200 mg Q2W (FAS)	-6.8	± 0.7
CZP 400 mg Q2W (FAS)	-6.8	± 0.7

Change From Baseline in Itch Numeric Rating Scale at Week 16 Secondary · Baseline and Week 16

This Outcome Measure applied to participants with moderate to severe chronic plaque Psoriasis (PSO). The Itch Numeric Rating Scale (NRS) has been developed as a simple, single item instrument to assess the patient-reported severity of itch at its most intense during the past 24h period. Participants indicate itch severity by circling the integer that best describes the worst level of itching due to PSO in the past 24h period on an 11-point scale anchored at 0, representing "no itching" and 10, representing "worst itch imaginable" (Kimball et al, 2016).

Group	Value	95% CI
Placebo (FAS)	0.2	± 0.5
CZP 200 mg Q2W (FAS)	-2.9	± 0.4
CZP 400 mg Q2W (FAS)	-4.0	± 0.3

Plasma Concentration of Certolizumab Pegol (CZP) Secondary · Blood samples were collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60

Plasma concentration was expressed in micrograms per milliliter (μg/mL). Values below Lower Limit of Quantification (LLOQ) were set to half the LLOQ to present summaries. The geometric mean and geometric coefficient of variation were only displayed if at least 2/3 of the data were above the LLOQ.

Baseline

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	NA	± NA
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	NA	± NA
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	NA	± NA

Week 2

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	34.6417	± 28.3
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	35.2588	± 25.2
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	33.2026	± 26.0

Week 4

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	47.9241	± 45.6
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	47.0462	± 35.7
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	48.3634	± 21.3

Week 6

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	36.3003	± 286.7
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	41.2410	± 183.0
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	52.4876	± 38.0

Week 8

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	21.9292	± 621.4
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	39.9282	± 243.7
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	33.4139	± 69.0

Week 12

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	16.1907	± 300.7
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	46.9934	± 189.3
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	23.8437	± 105.9

Week 16

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	14.5995	± 405.5
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	48.3156	± 183.8
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	18.1204	± 381.8

Week 24

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	26.2596	± 52.8
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	51.6911	± 118.2
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	7.7206	± 1747.5

Percentage of Participants With Positive Anti-Certolizumab Pegol-antibody Levels in Plasma Secondary · Blood samples will be collected at Baseline (Week 0) and at Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, 52, 60

A pre-anti-drug (CZP) antibody (ADA) positive subject was defined as having a confirmed positive sample at Baseline. A pre-ADA negative subject was defined as having a Screening below the cut point (BCP) sample, or a screening above the cut point (ACP) sample, but not confirmed positive at Baseline. A treatment-emergent ADA positive subject was defined as either 1) pre-ADA negative subjects having at least 1 ADA confirmed positive sample or 2) pre-ADA positive subjects with at least 1 sample with greater then or equal to (\>=) 1.67-fold increase from Baseline on CZP treatment.

Group	Value	95% CI
CZP 200 mg Q2W/CZP 200 mg Q2W (PK-PPS)	100
CZP 400 mg Q2W/CZP 400 mg Q2W (PK-PPS)	96.2
CZP 200 mg Q2W/CZP 400 mg Q4W (PK-PPS)	90.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) were collected from Baseline (Week 0) until the Safety Follow-up Visit (Week 60).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo (SS)

Serious: 1/26 (4%)

Deaths: 0/26

CZP 200mg Q2W (SS)

Serious: 2/72 (3%)

Deaths: 0/72

CZP 400mg Q4W (SS)

Serious: 0/20 (0%)

Deaths: 0/20

CZP 200 mg Q2W + CZP 400 mg Q4W (SS)

Serious: 2/72 (3%)

Deaths: 0/72

CZP 400 mg Q2W (SS)

Serious: 6/64 (9%)

Deaths: 0/64

All CZP (SS)

Serious: 8/122 (7%)

Deaths: 0/122

Serious adverse events (9 terms)

Reaction	System	Placebo (SS)	CZP 200mg Q2W (SS)	CZP 400mg Q4W (SS)	CZP 200 mg Q2W + CZP 400 m…	CZP 400 mg Q2W (SS)	All CZP (SS)
Latent tuberculosis	Infections and infestations	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Eyelid ptosis	Eye disorders	—	—	—	—	—	—
Large intestine polyp	Gastrointestinal disorders	—	—	—	—	—	—
Dental cyst	Gastrointestinal disorders	—	—	—	—	—	—
Sarcoidosis	Immune system disorders	—	—	—	—	—	—
Herpes zoster	Infections and infestations	—	—	—	—	—	—
Henoch-Schonlein purpura	Skin and subcutaneous tissue disorders	—	—	—	—	—	—

Other adverse events (35 terms — click to expand)

Reaction	System	Placebo (SS)	CZP 200mg Q2W (SS)	CZP 400mg Q4W (SS)	CZP 200 mg Q2W + CZP 400 m…	CZP 400 mg Q2W (SS)	All CZP (SS)
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—
Psoriasis	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Eczema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Folliculitis	Infections and infestations	—	—	—	—	—	—
Dermatitis contact	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Dental caries	Gastrointestinal disorders	—	—	—	—	—	—
Dermatophytosis of nail	Infections and infestations	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—
Dyshidrotic eczema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Ligament sprain	Injury, poisoning and procedural complications	—	—	—	—	—	—
Cell marker increased	Investigations	—	—	—	—	—	—
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—
Aortic valve incompetence	Cardiac disorders	—	—	—	—	—	—
Arrhythmia	Cardiac disorders	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—	—	—
Myringitis	Infections and infestations	—	—	—	—	—	—
Body tinea	Infections and infestations	—	—	—	—	—	—
Tinea versicolour	Infections and infestations	—	—	—	—	—	—
Meniscus injury	Injury, poisoning and procedural complications	—	—	—	—	—	—
Limb injury	Injury, poisoning and procedural complications	—	—	—	—	—	—
Type 2 diabetes mellitus	Metabolism and nutrition disorders	—	—	—	—	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Temporomandibular joint syndrome	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Sputum increased	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Essential hypertension	Vascular disorders	—	—	—	—	—	—
Orthostatic hypotension	Vascular disorders	—	—	—	—	—	—

Most-reported serious reactions: Latent tuberculosis, Neutropenia, Thrombocytopenia, Eyelid ptosis, Large intestine polyp, Dental cyst, Sarcoidosis, Herpes zoster.

Data from ClinicalTrials.gov NCT03051217 adverse events section.

Sponsor's own description

The purpose of this study is to demonstrate the efficacy and safety of Certolizumab Pegol (CZP) in the treatment of moderate to severe chronic plaque Psoriasis (PSO) in Japanese subjects.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Garcia-Doval I, Doney L, et al · · 2022 · cited 84× · PMID 35603936 · DOI 10.1002/14651858.cd011535.pub5
2. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Afach S, Doney L, et al · · 2020 · cited 78× · PMID 31917873 · DOI 10.1002/14651858.cd011535.pub3
3. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Guelimi R, Garcia-Doval I, et al · · 2023 · cited 67× · PMID 37436070 · DOI 10.1002/14651858.cd011535.pub6
4. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Garcia-Doval I, Doney L, et al · · 2021 · cited 54× · PMID 33871055 · DOI 10.1002/14651858.cd011535.pub4
5. Comparative Efficacy and Relative Ranking of Biologics and Oral Therapies for Moderate-to-Severe Plaque Psoriasis: A Network Meta-analysis.
   Armstrong AW, Soliman AM, Betts KA, Wang Y, et al · · 2021 · cited 46× · PMID 33788177 · DOI 10.1007/s13555-021-00511-1
6. Pustular Psoriasis: From Pathophysiology to Treatment.
   Genovese G, Moltrasio C, Cassano N, Maronese CA, et al · · 2021 · cited 40× · PMID 34944562 · DOI 10.3390/biomedicines9121746
7. Targeted Treatment for Erythrodermic Psoriasis: Rationale and Recent Advances.
   Shao S, Wang G, Maverakis E, Gudjonsson JE. · · 2020 · cited 31× · PMID 32180204 · DOI 10.1007/s40265-020-01283-2
8. Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: 52-Week Results.
   Umezawa Y, Asahina A, Imafuku S, Tada Y, et al · · 2021 · cited 19× · PMID 33886085 · DOI 10.1007/s13555-021-00520-0