Study to Assess the Immunogenicity, Safety, and Efficacy of High Capacity Process Etanercept in Rheumatoid Arthritis Subjects

A Single-arm, Open-label Study To Assess The Immunogenicity, Safety, And Efficacy Of Etanercept Manufactured Using The High Capacity Process Administered To Subjects With Rheumatoid Arthritis

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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Biological: etanercept

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • MHAT Plovdiv
  • Sofia, Bulgaria, 1431
    • DCC "Aleksandrovska" EOOD
  • Sofia, Bulgaria, 1612
    • UMHAT "Sv. Ivan Rilski" EAD, Sofia
  • Stara Zagora, Bulgaria, 6000
    • Medical Center - "New rehabilitation center" EOOD
• Croatia
  • Rijeka, Croatia, 51000
    • CHC Rijeka
  • Zagreb, Croatia, 10000
    • Medicinski Centar Kuna Peric
• Germany
  • Berlin, Germany, 14059
    • Schlosspark-Klinik, Innere Medizin II, Rheumatologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Vogelsang-Gommern, Germany, 39245
    • Immunologisches Zentrum Vogelsang-Gommern GmbH
  • Hessen
    • Frankfurt/Main, Hessen, Germany, 60528
      • Centrum für innovative Diagnostik und Therapie
  • Nordrhein-westfalen
    • Ratingen, Nordrhein-westfalen, Germany, 40882
      • Rheumaforschung - Studienambulanz Dr. Wassenberg
• Greece
  • Thessaloniki, Greece, 56429
    • Rheumatology Unit
  • Achaia
    • Rion Patras, Achaia, Greece, 26500
      • Rheumatology department
  • Crete
    • Heraklion, Crete, Greece, 71110
      • University Hospital of Heraklion
• Hungary
  • Budapest, Hungary, 1036
    • Qualiclinic Kft.
  • Kistarcsa, Hungary, 2143
    • Pest Megyei Flor Ferenc Korhaz
  • Nyiregyhaza, Hungary, 4400
    • Szabolcs-Szatmar-Bereg megyei
• Poland
  • Krakow, Poland, 31-501
    • Krakowskie Centrum Medyczne sp. Z.O.O
  • Nadarzyn, Poland, 05-830
    • NZOZ Lecznica MAK-MED s.c.
  • Poznan, Poland, 61-397
    • Prywatna Praktyka Lekarska Prof. UM dr hab.med. Pawel Hrycaj
  • Warszawa, Poland, 02-691
    • Reumatika-Centrum Reumatologii
• Serbia
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • Institute of Rheumatology
• Slovakia
  • Bratislava, Slovakia, 841 04
    • Reumatologicka ambulancia
  • Dunajska Streda, Slovakia, 929 01
    • AAGS, s.r.o.
  • Poprad, Slovakia, 058 01
    • Reumatologicka ambulancia, MUDr. Zuzana Cizmarikova, s.r.o.
  • Rimavska Sobota, Slovakia, 979 01
    • Reumex S.R.O.
  • Trnava, Slovakia, 917 01
    • REUMA-GLOBAL s.r.o.
  • Zilina, Slovakia, 010 01
    • Reumatologicka ambulancia
• South Africa
  • Cape Town
    • Panorama, Cape Town, South Africa, 7500
      • Panorama Medical Centre
  • Johannesburg
    • Parktown, Johannesburg, South Africa, 2193
      • Wits Clinical Research CMJAH Clinical Trial Site
  • Kwazulu-natal
    • Durban/Berea, Kwazulu-natal, South Africa, 4001
      • St. Augustines Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Prior treatment with etanercept.
• Presence of active infection or active or untreated tuberculosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ETN 50mg QW	Biological: etanercept; 50mg subcutaneous, once weekly, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Positive Etanercept Anti-Drug Antibody (ADA) Status at 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.	Week 12
Percentage of Participants With Positive Etanercept Anti-Drug Antibody Status at 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.	Week 24
Percentage of Participants With Positive Etanercept Anti-Drug Antibody Status: Throughout Study Treatment	Participants who developed anti-drug antibodies after treatment with Etanercept were evaluated. Percentage of participants with positive Etanercept anti-drug antibodies were summarized.	Baseline up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Positive Etanercept Neutralizing Anti-Drug Antibody Status: Throughout Study Treatment	Percentage of participants with positive Etanercept neutralizing anti-drug antibodies were summarized.	Baseline (Day 1) up to Week 24
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Baseline (Day 1) up to Week 28 (Follow-up)
Number of Participants With Investigator-Identified Serious Infections	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.	Baseline (Day 1) up to Week 28 (Follow-up)
Number of Participants With Injection Site Reactions	Injection site reactions included injection site erythema, swelling, pain and warmth.	Baseline (Day 1) up to Week 28 (Follow-up)
Number of Participants With Grade 3 and 4 Clinical Laboratory Abnormalities	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).	Baseline (Day 1) up to Week 28 (Follow-up)
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response	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.	Week 4, 12, 24
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response	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.	Week 4, 12, 24
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response	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.	Week 4, 12, 24
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	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.	Baseline, Week 4, 12, 24
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	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.	Baseline, Week 4, 12, 24
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 4, 12 and 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.	Baseline, Week 4, 12, 24

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Polak P, Peric P, Louw I, Gaylord SM, Williams T, Becker JC, Pedersen R, Korth-Bradley J, Vlahos B. A single-arm, open-label study to assess the immunogenicity, safety, and efficacy of etanercept manufactured using the serum-free, high-capacity manufacturing process administered to patients with rheumatoid arthritis. Eur J Rheumatol. 2019 Jan;6(1):23-28. doi: 10.5152/eurjrheum.2018.18078.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: February 13, 2015
• First Submitted That Met QC Criteria: February 26, 2015
• First Posted (Estimate): March 4, 2015

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: May 10, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: B1801359; 2013-004569-16 (EudraCT Number)