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

Arthritis, Rheumatoid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02378506
• Other study ID #: B1801359
• Secondary ID: 2013-004569-16
• Status: Completed
• Phase: Phase 3
• First received: February 13, 2015
• Last updated: May 10, 2017
• Start date: April 2015
• Est. completion date: June 2016

Study information

• Verified date: March 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: June 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Biological:
• etanercept
50mg subcutaneous, once weekly, 24 weeks

Locations

Country	Name	City	State
Bulgaria	MHAT Plovdiv	Plovdiv
Bulgaria	DCC "Aleksandrovska" EOOD	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski" EAD, Sofia	Sofia
Bulgaria	Medical Center - "New rehabilitation center" EOOD	Stara Zagora
Croatia	Chc Rijeka	Rijeka
Croatia	Medicinski Centar Kuna Peric	Zagreb
Germany	Schlosspark-Klinik, Innere Medizin II, Rheumatologie	Berlin
Germany	Centrum für innovative Diagnostik und Therapie	Frankfurt/Main	Hessen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Rheumaforschung - Studienambulanz Dr. Wassenberg	Ratingen	Nordrhein-westfalen
Germany	Immunologisches Zentrum Vogelsang-Gommern GmbH	Vogelsang-Gommern
Greece	University Hospital of Heraklion	Heraklion	Crete
Greece	Rheumatology Department	Rion Patras	Achaia
Greece	Rheumatology Unit	Thessaloniki
Hungary	Qualiclinic Kft.	Budapest
Hungary	Pest Megyei Flor Ferenc Korhaz	Kistarcsa
Hungary	Szabolcs-Szatmar-Bereg megyei	Nyiregyhaza
Poland	Krakowskie Centrum Medyczne sp. Z.O.O	Krakow
Poland	NZOZ Lecznica MAK-MED s.c.	Nadarzyn
Poland	Prywatna Praktyka Lekarska Prof. UM dr hab.med. Pawel Hrycaj	Poznan
Poland	Reumatika-Centrum Reumatologii	Warszawa
Serbia	Institute of Rheumatology	Belgrade	Beograd
Slovakia	Reumatologicka ambulancia	Bratislava
Slovakia	AAGS, s.r.o.	Dunajska Streda
Slovakia	Reumatologicka ambulancia, MUDr. Zuzana Cizmarikova, s.r.o.	Poprad
Slovakia	REUMEX s.r.o.	Rimavska Sobota
Slovakia	REUMA-GLOBAL s.r.o.	Trnava
Slovakia	Reumatologicka ambulancia	Zilina
South Africa	St. Augustines Hospital	Durban/Berea	Kwazulu-natal
South Africa	Panorama Medical Centre	Panorama	Cape Town
South Africa	Wits Clinical Research CMJAH Clinical Trial Site	Parktown	Johannesburg

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Bulgaria,  Croatia,  Germany,  Greece,  Hungary,  Poland,  Serbia,  Slovakia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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