Efficacy And Safety Of Tofacitinib In Chinese Subjects With Active Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

Official title:

A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF TOFACITINIB (CP-690,550) IN CHINESE SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS AND AN INADEQUATE RESPONSE TO AT LEAST ONE CONVENTIONAL SYNTHETIC DMARD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03486457
• Other study ID #: A3921234
• Status: Completed
• Phase: Phase 3
• Start date: August 10, 2018
• Est. completion date: April 28, 2021

Study information

• Verified date: June 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 6 month study investigating the effectiveness and safety of tofacitinib in treating signs and symptoms and improving physical function in Chinese patients with active psoriatic arthritis and had inadequate response to a conventional synthetic disease modifying anti-rheumatic drug. This is a China alone study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 204
• Est. completion date: April 28, 2021
• Est. primary completion date: April 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chinese patients
• Active arthritis at screening/baseline as indicated by >/= 3 tender/painful and 3 swollen joints
• Active plaque psoriasis at screening
• Inadequate response to at least one conventional synthetic DMARD

Exclusion Criteria:

• Non-plaque forms of psoriasis (with exception of nail psoriasis)
• History of autoimmune rheumatic disease other than PsA; also prior history of or current, rheumatic inflammatory disease other than PsA

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• Tofacitinib
tablets, 5 mg BID x 6 months

Other:
• Placebo
tablets, to match tofacitinib 5 mg BID x 3 months

Drug:
• Tofacitinib
tablets, 5 mg BID x 3 months

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Rheumatology and Immunology Department, Xuanwu Hospital Capital Medical University	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	The First hospital of Jilin University	Changchun	Jilin
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Department of Rheumatology, The First People's Hospital of Changzhou	Changzhou	Jiangsu
China	Department of Rheumatology and Immunology,West China Hospital,Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital of Army Medical University, PLA	Chongqing	Chongqing
China	Guangdong Second Provincial General Hospital	Guangzhou	Guangdong
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Rheumatology Department, The first Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The First Affiliated Hospital of Anhui Medical University/Rheumatology Department	Hefei	Anhui
China	Jiu Jiang No.1 People's Hospital	Jiujiang	Jiangxi
China	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Linyi People's Hospital	Linyi	Shandong
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	Pingxiang People's Hospital	Pingxiang	Jiangxi
China	Huashan Hospital, Fudan University	Shanghai
China	Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	The Third Hospital of Hebei Medical University, Rheumatology and Immunology Department	Shijiazhuang	Hebei
China	Department of Rheumatology ,The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin Medical University General Hospital, Rheumatology and Immunology Department	Tianjin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Department of Rheumatology, Northern Jiangsu People's Hospital	Yangzhou	Jiangsu
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Zhuzhou Central Hospital	Zhuzhou	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 3	ACR50 response: greater than or equal to (=) 50% improvement in tender (TJC) and swollen joint counts (SJC) and =50% improvement in 3 of the 5 remaining ACR-core set measures: patient (PtGA) and physician global assessments (PhyGA), pain, disability (Health Assessment Questionnaire - Disability Index [HAQ-DI], scored from 0 to 3), and an acute-phase reactant (C-reactive protein [CRP]). TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 millimeter (mm).	Month 3
Secondary	Percentage of Participants Achieving ACR20 Response at Week 2, Month 1, 2, 3, 4, and 6	ACR20 response:=20% improvement in TJC and SJC and =20% improvement in 3 of the 5 remaining ACR-core set measures: PtGA and PhyGA, pain, disability (HAQ-DI, scored from 0 to 3), and a CRP. TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 mm.	Week 2, Month 1, 2, 3, 4, and 6
Secondary	Percentage of Participants Achieving ACR70 Response at Week 2, Month 1, 2, 3, 4, and 6	ACR70 response:=70% improvement in TJC and SJC and =70% improvement in 3 of the 5 remaining ACR-core set measures: PtGA and PhyGA, pain, disability (HAQ-DI, scored from 0 to 3), and a CRP. TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 mm.	Week 2, Month 1, 2, 3, 4, and 6
Secondary	Percentage of Participants Achieving ACR50 Response at Week 2, Month 1, 2, 4, and 6	ACR50 response:=50% improvement in TJC and SJC and =50% improvement in 3 of the 5 remaining ACR-core set measures: PtGA and PhyGA, pain, disability (HAQ-DI, scored from 0 to 3), and a CRP. TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 mm.	Week 2, Month 1, 2, 4, and 6
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 2, Month 1, 2, 3, 4, and 6	The HAQ-DI assessed the degree of difficulty a participant had experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty," 1 as "some difficulty," 2 as "much difficulty," and 3 as "unable to do". The HAQ-DI score was the average of the non-missing domain scores. If >2 domain scores were missing, HAQ-DI score was considered missing. A higher score represented a more limited physical functional status/ability.	Baseline, Week 2, Month 1, 2, 3, 4, and 6
Secondary	HAQ-DI Response (Decrease From Baseline =0.30) Rate for Participants With Baseline HAQ-DI =0.30 at Week 2, Month 1, 2, 3, 4, and 6	Rate was measured in terms of percentage of participants with HAQ-DI response. The HAQ-DI assessed the degree of difficulty a participant had experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty," 1 as "some difficulty," 2 as "much difficulty," and 3 as "unable to do". The HAQ-DI score was the average of the non-missing domain scores. If >2 domain scores were missing, HAQ-DI score was considered missing. A higher score represented a more limited physical functional status/ability.	Week 2, Month 1, 2, 3, 4, and 6
Secondary	HAQ-DI Response (Decrease From Baseline =0.35) Rate for Participants With Baseline HAQ-DI =0.35 at Week 2, Month 1, 2, 3, 4, and 6	Rate was measured in terms of percentage of participants with HAQ-DI response. The HAQ-DI assessed the degree of difficulty a participant had experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty," 1 as "some difficulty," 2 as "much difficulty," and 3 as "unable to do". The HAQ-DI score was the average of the non-missing domain scores. If >2 domain scores were missing, HAQ-DI score was considered missing. A higher score represented a more limited physical functional status/ability.	Week 2, Month 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Swollen Joint Count at Week 2, Month 1, 2, 3, 4, and 6	Swollen joint count was an assessment on 66 joints (temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeals, thumb interphalangeal, proximal interphalangeals, distal interphalangeals, knee, ankle, tarsus, metatarsophalangeals, great toe interphalangeal, proximal and distal interphalangeals combined). Artificial joints were not assessed. Each joint was assessed for swelling as: Present/Absent/Not Done/Not Applicable (used for artificial or missing joints).	Baseline, Week 2, Month 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Tender/Painful Joint Count at Week 2, Month 1, 2, 3, 4, and 6	Tender/painful joint count was an assessment on 68 joints (temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeals, thumb interphalangeal, proximal interphalangeals, distal interphalangeals, hip, knee, ankle, tarsus, metatarsophalangeals, great toe interphalangeal, proximal and distal interphalangeals combined). Artificial joints were not assessed. Each joint was assessed for tenderness/pain as: Present/Absent/Not Done/Not Applicable (used for artificial or missing joints).	Baseline, Week 2, Month 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Patient's Assessment of Arthritis Pain Visual Analog Scale (VAS) at Week 2, Month 1, 2, 3, 4, and 6	Participants were assessed the severity of their arthritis pain using a 100 mm VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain).	Baseline, Week 2, Month 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Patient's Global Assessment of Arthritis (VAS) at Week 2, Month 1, 2, 3, 4, and 6	Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (Very well) and 100 (Very poorly).	Baseline, Week 2, Month 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Physician's Global Assessment of Arthritis (VAS) at Week 2, Month 1, 2, 3, 4, and 6	The blinded investigator or qualified assessor assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination, and should be independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (Very good) and 100 (Very poor).	Baseline, Week 2, Month 1, 2, 3, 4, and 6
Secondary	Change From Baseline in CRP at Week 2, Month 1, 2, 3, 4, and 6	Blood samples were collected at each visit (except follow-up) for analysis of CRP using an assay by the central laboratory. The test for CRP was a laboratory measurement for evaluation of an acute phase reactant of inflammation. A decrease in the level of CRP indicated reduction in inflammation and therefore improvement.	Baseline, Week 2, Month 1, 2, 3, 4, and 6
Secondary	Physician's Global Assessment of Psoriasis (PGA-PsO) Response Rates for Participants With Baseline PGA-PsO =2 at Month 1, 3 and 6	PGA-PsO response : PGA-PsO = 0 or 1 and decrease from baseline in PGA-PsO =2. Rate was measured in terms of percentage of participants with PGA-PsO response. The PGA-PsO was scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. Average erythema, induration and scaling were scored separately over the whole body according to a 5-point severity scale, scored as 0 (none), 1, 2, 3, or 4 (most severe). The severity scores were summed and averaged after which the total average was rounded to the nearest whole number score to determine the PGA-PsO score.	Month 1, 3 and 6
Secondary	Change From Baseline in PGA-PsO for Participants With Baseline PGA-PsO>0 at Month 1, 3 and 6	The PGA-PsO was scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. Average erythema, induration and scaling were scored separately over the whole body according to a 5-point severity scale, scored as 0 (none), 1, 2, 3, or 4 (most severe). The severity scores were summed and averaged after which the total average was rounded to the nearest whole number score to determine the PGA-PsO score.	Baseline, Month 1, 3 and 6
Secondary	Psoriasis Area and Severity Index (PASI) 75 Response Rates at Month 1, 3 and 6 in Participants With Baseline Psoriatic Body Surface Area (BSA) =3% and Baseline PASI >0	PASI75 response: =75% improvement from baseline in PASI. Rate was measured in terms of percentage of participants with PASI75 response. PASI quantified the severity of a participant's psoriasis based on both lesion severity and the percent of BSA affected. PASI score ranged from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI was only performed if =3% of participant's BSA was affected at baseline.	Month 1, 3 and 6
Secondary	Percent Change From Baseline in PASI Score at Month 1, 3 and 6 for Participants With Baseline BSA =3% and Baseline PASI >0	PASI quantified the severity of a participant's psoriasis based on both lesion severity and the percentage of BSA affected. PASI was a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of four body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. PASI score ranged from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI was only performed if =3% of participant's BSA was affected at baseline.	Baseline, Month 1, 3 and 6
Secondary	Percent Change From Baseline in PASI Clinical Component Scores at Month 1, 3 and 6 for Participants With Baseline BSA =3% and Baseline PASI >0	PASI quantified the severity of a participant's psoriasis based on both lesion severity and the percentage of BSA affected. PASI was a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of four body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. PASI was only performed if =3% of participant's BSA was affected at baseline. The PASI clinical component scores (erythema, induration and scaling) range from 0.0 to 24.0, with higher scores representing increasing severity of psoriasis.	Baseline, Month 1, 3 and 6
Secondary	Percent Change From Baseline in BSA at Month 1, 3 and 6 for Participants With Baseline BSA >0%	Assessment of BSA with psoriasis was performed separately for four body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The BSA with psoriasis (%) was the sum of the numbers of the handpoints across the 4 body regions.	Baseline, Month 1, 3 and 6
Secondary	Change From Baseline in Physician's Global Assessment of Psoriatic Arthritis (PGA-PsA) (VAS) at Month 1, 3 and 6	The blinded investigator or qualified assessor assessed how the participant's overall PsA appeared at the time of the visit. The investigator's response was recorded using a 100 mm VAS (Not active at all to Extremely active).	Baseline, Month 1, 3 and 6
Secondary	Resolution Rate of Dactylitis at Month 1, 3 and 6 for Participants With Baseline Dactylitis Severity Score (DSS) >0	Dactylitis was characterized by swelling of the entire finger or toe. The DSS was a function of finger circumference and tenderness, assessed and summed across all dactylitis digits.; Resolution rate of dactylitis was defined as achieving DSS =0. Rate was measured in terms of percentage of participants with resolution of dactylitis.; Dactylitis severity was scored based upon digit tenderness using a scale of 0-3, where 0 = no tenderness and 3 = extreme tenderness, in each digit of the hands and feet. DSS was the sum of the severity of the 20 evaluated digits. The range of total dactylitis scores for a participant would be 0-60 (with a higher score indicating more severe dactylitis).	Month 1, 3 and 6
Secondary	Change From Baseline in DSS for Participant With Baseline DSS >0 at Month 1, 3 and 6	Dactylitis was characterized by swelling of the entire finger or toe. The DSS was a function of finger circumference and tenderness, assessed and summed across all dactylitis digits.; Dactylitis severity was scored based upon digit tenderness using a scale of 0-3, where 0 = no tenderness and 3 = extreme tenderness, in each digit of the hands and feet. DSS was the sum of the severity of the 20 evaluated digits. The range of total dactylitis scores for a participant would be 0-60 (with a higher score indicating more severe dactylitis).	Baseline, Month 1, 3 and 6
Secondary	Resolution Rate of Enthesitis at Month 1, 3 and 6 for Participants With Baseline Leeds Enthesitis Index (LEI) >0	Resolution rate of enthesitis was defined as percentage of participants achieving enthesitis score (using LEI) =0.; Rate was measured in terms of percentage of participants with resolution of enthesitis.; Enthesitis score based upon presence/absence of enthesitis at 6 sites using LEI. Six sites, including (right and left): lateral epicondyle humerus, medial femoral condyle and Achilles tendon insertion, were assessed for enthesitis. LEI was the number of sites with presence of enthesitis.	Month 1, 3 and 6
Secondary	Change From Baseline in LEI for Participant With Baseline LEI >0 at Month 1, 3 and 6	Enthesitis score based upon presence/absence of enthesitis at 6 sites using LEI. Six sites, including (right and left): lateral epicondyle humerus, medial femoral condyle and Achilles tendon insertion, were assessed for enthesitis. LEI was the number of sites with presence of enthesitis.	Baseline, Month 1, 3 and 6
Secondary	Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score at Month 1, 3 and 6 for Participants With Baseline NAPSI >0	A target finger nail was evaluated using NAPSI scale. Each quadrant of the target nail was graded for nail matrix psoriasis and nail bed psoriasis, giving that 1 target nail a score of 0-8. At the baseline visit, the worst case fingernail was chosen and the same nail evaluated consistently through the entire study.	Baseline, Month 1, 3 and 6
Secondary	Percentage of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC) at Week 2, Month 1, 2, 3, 4, and 6	The PsARC consisted of 4 measurements: Tender Joint Count (68), Swollen Joint Count (66), Physician's Global Assessment of Arthritis (VAS) (0-100 mm), Patient's Global Assessment of Arthritis (VAS) (0-100 mm). In order to be a 'PsARC responder', participant must achieve improvement in 2 of 4 measures, one of which must be joint pain or swelling, without worsening in any measure.	Week 2, Month 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Disease Activity Score (DAS)28-3 (CRP) at Week 2, Month 1, 2, 3, 4, and 6	The DAS was a derived measurement with differential weighting given to each component. The components of the DAS 28-3 arthritis assessment were: Tender/Painful Joint Count (28), Swollen Joint Count (28), CRP (refer to above OMs for more details of these components). DAS28 scores range from 0 to 9.4. A DAS28-3 (CRP) score higher than 5.1 indicates high disease activity, a DAS28-3 (CRP) score less than 3.2 indicates low disease activity, and a DAS28-3 (CRP) score less than 2.6 indicates clinical remission. A higher score represented a more severe disease activity, and a negative change from baseline indicates improvement.; DAS28-3(CRP)=[0.56*sqrt(TJC28)+0.28*sqrt(SJC28)+0.36*ln(CRP+1)]*1.10+1.15, where sqrt() refers to the square root, and ln() refers to the natural logarithm.	Baseline, Week 2, Month 1, 2, 3, 4, and 6
Secondary	Change From Baseline in Short-Form-36 Health Survey (SF-36) Version 2, Acute at Month 1, 3 and 6	The SF 36 v.2 (Acute) was a 36 item generic health status measure. It measured 8 general health domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. These domains were summarized as physical and mental component summary scores. The score range for the physical and mental health scores was 0-100 (100=highest level of functioning).	Baseline, Month 1, 3 and 6
Secondary	Change From Baseline in EuroQol 5 Dimensions 3 Levels (EQ-5D-3L) Domain Scores at Month 1, 3 and 6	On the EQ-5D (participant version, 3 categories of response per question), 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) were assessed. The status of each dimension had three possible responses with the corresponding scores of 1 (no problem), 2 (some problems) and 3 (severe problems).	Baseline, Month 1, 3 and 6
Secondary	Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score at Month 1, 3 and 6	The EQ-VAS recorded the patient's self-rated health on a vertical visual analogue scale where the endpoint was labelled 'Best imaginable health state' and 'Worst imaginable health state'. Based on the patient's mark on the VAS form a score ranging from 0 to 100 mm was recorded.	Baseline, Month 1, 3 and 6
Secondary	Change From Baseline in Work Productivity and Activity Impairment-Psoriatic Arthritis (WPAI-PsA) at Month 3 and 6: Work Time Missed, Impairment While Working, Overall Work Impairment	The WPAI-PsA was a 6-item questionnaire that measured absenteeism (work time missed), presenteesism (impairment at work/reduced on -the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism) and activity impairment. WPAI-PsA outcomes were expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.	Baseline, Month 3 and 6
Secondary	Change From Baseline in WPAI-PsA at Month 3 and 6: Activity Impairment	The WPAI-PsA was a 6-item questionnaire that measured absenteeism (work time missed), presenteesism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism) and activity impairment. WPAI-PsA outcomes were expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.	Baseline, Month 3 and 6

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