Study to Assess the Immunogenicity, Safety, and Efficacy of High Capacity Process Etanercept in Rheumatoid Arthritis Subjects
- Conditions
- Arthritis, Rheumatoid
- Interventions
- Biological: etanercept
- Registration Number
- NCT02378506
- Lead Sponsor
- Pfizer
- Brief Summary
Open-label immunogenicity, safety and efficacy study of etanercept manufactured using the high capacity process. Descriptive results will be provided however a formal hypothesis will not be tested in this trial.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 188
- Moderate to severe active disease with presence of at least 4 tender joints and 4 swollen joints.
- Either the patient or a designee must be capable of administering the subcutaneous injection of study drug.
- Prior treatment with etanercept.
- Presence of active infection or active or untreated tuberculosis.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ETN 50mg QW etanercept -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Positive Etanercept Anti-Drug Antibody (ADA) Status at Week 12 Week 12 Participants who developed anti-drug antibodies after treatment with Etanercept were evaluated. Percentage of participants with positive Etanercept anti-drug antibodies were summarized.
Percentage of Participants With Positive Etanercept Anti-Drug Antibody Status at Week 24 Week 24 Participants who developed anti-drug antibodies after treatment with Etanercept were evaluated. Percentage of participants with positive Etanercept anti-drug antibodies were summarized.
Percentage of Participants With Positive Etanercept Anti-Drug Antibody Status: Throughout Study Treatment Baseline up to Week 24 Participants who developed anti-drug antibodies after treatment with Etanercept were evaluated. Percentage of participants with positive Etanercept anti-drug antibodies were summarized.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Positive Etanercept Neutralizing Anti-Drug Antibody Status: Throughout Study Treatment Baseline (Day 1) up to Week 24 Percentage of participants with positive Etanercept neutralizing anti-drug antibodies were summarized.
Number of Participants With Investigator-Identified Serious Infections Baseline (Day 1) up to Week 28 (Follow-up) Infection was considered as serious by investigator for any of the following outcomes: death; life-threatening; required initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity or congenital anomaly/birth defect.
Number of Participants With Grade 3 and 4 Clinical Laboratory Abnormalities Baseline (Day 1) up to Week 28 (Follow-up) Laboratory abnormalities(national cancer institute toxicity criteria version 4.0),Grade 3:neutrophil (greater than or equal to\[\>=\]0.5,less than\[\<\]1.0 10\^9/L),lymphocyte (\<0.5 10\^9/L),hemoglobin (Hb) (\<80,\>=65 gram per liter \[g/L\]),platelet(\<50.0,\>=25.0 10\^9/L),white blood count(WBC) (\<2.0, \>=1.0 10\^9/L);alkaline phosphatase (AP),aspartate aminotransferase(AST),alanine aminotransferase(ALT) (greater than\[\>\]5.0\*upper range \[UR\], \<=20.0\*UR unit per liter\[U/L\]);bilirubin(\>1.5\*UR, less than or equal to\[\<=\]3.0\*UR micromole per liter\[mcmol/L\]);creatinine(\>3.0\*UR, \<=6.0\*UR mcmol/L);albumin (\<20.0 g/L),urea(\>3.0\*UR, \<=4.0\*UR g/L);potassium (K)-high,low (\>6.0,\<=7.0or\<3.0,\>=2.5 mcmol/L); sodium(Na)-high,low(\>155, \<=160 or \<130, \>=120 mcmol/L)and Grade 4: neutrophil(\<0.5 10\^9/L),Hb (\<65 g/L);platelet (\<25.0 10\^9/L); WBC(\<1.0 10\^9/L);AP,AST,ALT(\>20.0\*UR U/L);bilirubin(\>3.0\*UR mcmol/L);creatinine (\>6.0\*UR mcmol/L);urea (\>4.0\*UR g/L);K-high,low (\>7.0or\<2.5 mcmol/L);Na-high, low (\>160or\<120 mcmol/L).
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline (Day 1) up to Week 28 (Follow-up) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
Number of Participants With Injection Site Reactions Baseline (Day 1) up to Week 28 (Follow-up) Injection site reactions included injection site erythema, swelling, pain and warmth.
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response Week 4, 12, 24 ACR20 responder: participants with 20 percent (%) improvement in tender and swollen 28-joint counts and 20% improvement in at least 3 of the 5 measures: participant global assessment of arthritis (PtGA), physician global assessment of arthritis (PGA), participant pain visual analogue scale (Pain-VAS), health assessment questionnaire-disability index (HAQ-DI) and C-reactive protein. PtGA: participant assessed overall disease activity, score: 0 (no arthritis) to 10 (extreme arthritis), higher score=more arthritis. PGA: physician judged participant's overall disease activity, score: 0 (no arthritis) to 10 (extreme arthritis), higher score=more arthritis. Pain-VAS: participant assessed arthritis pain by 100 millimeter (mm) VAS, score: 0 mm (no pain) to 100 mm (extreme pain), higher score=more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score=more disability. Percentage of participants with ACR20 response were reported.
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response Week 4, 12, 24 ACR50 responder: participants with 50% improvement in tender and swollen 28-joint counts and 50% improvement in at least 3 of the 5 measures: participant global assessment of arthritis (PtGA), physician global assessment of arthritis (PGA), participant pain visual analogue scale (Pain-VAS), health assessment questionnaire-disability index (HAQ-DI) and C-reactive protein. PtGA: participant assessed overall disease activity, score: 0 (no arthritis) to 10 (extreme arthritis), higher score=more arthritis. PGA: physician judged participant's overall disease activity, score: 0 (no arthritis) to 10 (extreme arthritis), higher score=more arthritis. Pain-VAS: participant assessed arthritis pain by 100 millimeter (mm) VAS, score: 0 mm (no pain) to 100 mm (extreme pain), higher score=more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score=more disability. Percentage of participants with ACR50 response were reported.
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response Week 4, 12, 24 ACR70 responder: participants with 70% improvement in tender and swollen 28-joint counts and 70% improvement in at least 3 of the 5 measures: participant global assessment of arthritis (PtGA), physician global assessment of arthritis (PGA), participant pain visual analogue scale (Pain-VAS), health assessment questionnaire-disability index (HAQ-DI) and C-reactive protein. PtGA: participant assessed overall disease activity, score: 0 (no arthritis) to 10 (extreme arthritis), higher score=more arthritis. PGA: physician judged participant's overall disease activity, score: 0 (no arthritis) to 10 (extreme arthritis), higher score=more arthritis. Pain-VAS: participant assessed arthritis pain by 100 millimeter (mm) VAS, score: 0 mm (no pain) to 100 mm (extreme pain), higher score=more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score=more disability. Percentage of participants with ACR70 response were reported.
Change From Baseline in Disease Activity Scale Based on 28 Joint Count Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Week 4, 12 and 24 Baseline, Week 4, 12, 24 DAS28: measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from number of swollen joints (SJC) and tender joints (TJC ) using the 28 joints count, erythrocyte sedimentation rate (millimeter per hour \[mm/hour\]) and participant's general health visual analog scale assessment (scores: 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score: 0 (none) to 10 (extreme disease activity), higher scores indicate more disease activity. DAS28-4 (ESR) less than (\<) 2.6= remission, \<3.2= low disease activity, greater than or equal to (\>=) 3.2 to 5.1= moderate disease activity and \>5.1= high disease activity.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 4, 12 and 24 Baseline, Week 4, 12, 24 HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each item scored on 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.
Change From Baseline in Disease Activity Scale Based on 28 Joint Count C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Week 4, 12 and 24 Baseline, Week 4, 12, 24 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from the number of swollen joints and tender joints using the 28 joints count, C-Reactive protein (milligram per liter \[mg/L\]) and participant's general health visual analog scale assessment (scores ranging 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 10 (extreme disease activity), higher scores indicate more disease activity. DAS28-4 (CRP) less than (\<) 2.6= remission, \<3.2= low disease activity, greater than or equal to (\>=) 3.2 to 5.1= moderate disease activity and \>5.1= high disease activity.
Trial Locations
- Locations (30)
UMHAT "Sv. Ivan Rilski" EAD, Sofia
🇧🇬Sofia, Bulgaria
Medical Center - "New rehabilitation center" EOOD
🇧🇬Stara Zagora, Bulgaria
Medicinski Centar Kuna Peric
🇭🇷Zagreb, Croatia
Rheumaforschung - Studienambulanz Dr. Wassenberg
🇩🇪Ratingen, Nordrhein-westfalen, Germany
Rheumatology Department
🇬🇷Rion Patras, Achaia, Greece
University Hospital of Heraklion
🇬🇷Heraklion, Crete, Greece
Pest Megyei Flor Ferenc Korhaz
🇭🇺Kistarcsa, Hungary
Krakowskie Centrum Medyczne sp. Z.O.O
🇵🇱Krakow, Poland
Reumatologicka ambulancia
🇸🇰Zilina, Slovakia
REUMA-GLOBAL s.r.o.
🇸🇰Trnava, Slovakia
Reumatologicka ambulancia, MUDr. Zuzana Cizmarikova, s.r.o.
🇸🇰Poprad, Slovakia
Wits Clinical Research CMJAH Clinical Trial Site
🇿🇦Parktown, Johannesburg, South Africa
Panorama Medical Centre
🇿🇦Panorama, Cape Town, South Africa
St. Augustines Hospital
🇿🇦Durban/Berea, Kwazulu-natal, South Africa
Szabolcs-Szatmar-Bereg megyei
🇭🇺Nyiregyhaza, Hungary
Immunologisches Zentrum Vogelsang-Gommern GmbH
🇩🇪Vogelsang-Gommern, Germany
MHAT Plovdiv
🇧🇬Plovdiv, Bulgaria
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Reumatika-Centrum Reumatologii
🇵🇱Warszawa, Poland
REUMEX s.r.o.
🇸🇰Rimavska Sobota, Slovakia
Centrum für innovative Diagnostik und Therapie
🇩🇪Frankfurt/Main, Hessen, Germany
Rheumatology Unit
🇬🇷Thessaloniki, Greece
NZOZ Lecznica MAK-MED s.c.
🇵🇱Nadarzyn, Poland
Schlosspark-Klinik, Innere Medizin II, Rheumatologie
🇩🇪Berlin, Germany
DCC "Aleksandrovska" EOOD
🇧🇬Sofia, Bulgaria
Chc Rijeka
🇭🇷Rijeka, Croatia
Prywatna Praktyka Lekarska Prof. UM dr hab.med. Pawel Hrycaj
🇵🇱Poznan, Poland
Institute of Rheumatology
🇷🇸Belgrade, Beograd, Serbia
AAGS, s.r.o.
🇸🇰Dunajska Streda, Slovakia
Qualiclinic Kft.
🇭🇺Budapest, Hungary