Clinical Trial to Compare Treatment With GP2017 and Humira® in Patients With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— ADMYRA  

Official title:

A Randomized, Double-blind, Parallel-group, Multicenter Study to Demonstrate Similar Efficacy and to Compare Safety and Immunogenicity of GP2017 and Humira® in Patients With Moderate to Severe Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02744755
• Other study ID #: GP17-302
• Secondary ID: 2015-003433-10
• Status: Completed
• Phase: Phase 3
• Start date: March 31, 2016
• Est. completion date: September 26, 2017

Study information

• Verified date: November 2018
• Source: Sandoz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Clinical trial to compare treatment with GP2017 and Humira® in patients with Rheumatoid Arthritis

Description:

The purpose of this study is to demonstrate similar efficacy and safety of GP2017 and US-licensed Humira® in patients with moderate to severe rheumatoid arthritis (RA) with inadequate response to Disease modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: September 26, 2017
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must have been diagnosed with RA = 6 months prior to screening

2. Patients must have active disease, defined as DAS28-CRP = 3.2 at the time of screening

3. Patients must have CRP levels above 5mg/l or ESR levels above the upper limits of normal

4. Patients must have had inadequate clinical response to MTX 10 - 25 mg/week

Exclusion Criteria:

1. Previous treatment with adalimumab, other anti-TNFa therapies or cell depleting agents, e.g. anti-CD20 therapy

2. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during treatment

3. Nursing (lactating) or pregnant women

4. History of or ongoing inflammatory or autoimmune diseases other than RA, e.g. mixed connective tissue disease, systemic lupus erythematosus etc.

5. Systemic corticosteroids > 7.5mg/day within 4 weeks prior to baseline

6. History or presence of cancer or lymphoproliferative disease other than a successfully and completely treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix and/or removed non-invasive colon polyps, with no evidence of recurrence

7. History of uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (New York Heart Association III-IV), active peptic ulcer disease, recent stroke (within 3 months)

8. Subject known to have immune deficiency, history of positive human immunodeficiency virus (HIV) status or immunocompromised for other reasons

9. History of clinically significant hematologic (e.g. severe anemia, leucopenia, thrombocytopenia), renal or liver disease (e.g. glomerulonephritis, fibrosis, cirrhosis, hepatitis)

10. History of persistent chronic infection; recurrent infection or active infections

11. History of tuberculosis, presence of active tuberculosis, latent tuberculosis as detected by imaging (e.g. chest X-ray, chest Computerized Tomography(CT) scan, Magnetic Resonance Imaging (MRI)) and/ or positive QuantiFERON-TB Gold test (QFT)

12. History or evidence of opportunistic infections, e.g. histoplasmosis, listeriosis, legionellosis

13. Positive serology Hepatitis B (either HBsAg or anti-HBc) or Hepatitis C (positive HCV-Ab or HCV-RNA) indicative of previous or current infections

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• Adalimumab - GP2017
Adalimumab - GP2017
• Adalimumab - US licensed Humira
Adalimumab - US licensed Humira

Locations

Country	Name	City	State
Czechia	IMEDICA s.r.o.	Brno
Czechia	Revmatologicka a interni ambulance	Kladno
Czechia	Revmatologicky Ustav	Praha 2
Czechia	MEDICAL PLUS s.r.o.	Uherske Hradiste
Czechia	Revmacentrum MUDr. Mostera s.r.o.	Zidenice
Germany	Rheumatologische Schwerpunktpraxis Steglitz	Berlin
Germany	HRF Hamburger Rheuma Forschungszentrum	Hamburg
Germany	Praxis Dr. Walter	Rendsburg	Schleswig Holstein
Hungary	Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz	Bekescsaba
Hungary	Sopron Medical Egeszsegugyi Szolgaltato Kft.	Budapest
Hungary	Hevizgyogyfurdo es Szent Andras Reumakorhaz Reumatologia III	Heviz
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz Reumatologiai Osztaly	Nyiregyhaza
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged
Hungary	Vital Medical Center	Veszprem
Italy	Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)	Milano
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte UOC Reumatologia	Siena
Malaysia	Hospital Selayang	Batu Caves	Selangor
Malaysia	Hospital Pulau Pinang	George Town	Pulau Pinang
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh	Perak
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bahru	Kelantan
Malaysia	Hospital Sibu	Sibu	Sarawak
Mexico	Investigacion y Biomedicina de Chihuahua, S.C.	Chihuahua
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango
Mexico	Centro Investigacion en Artritis y Osteoporosis S.C.	Mexicali	Baja California Norte
Mexico	RM Pharma Specialists SA de CV	Mexico
Mexico	Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.	San Luis Potosi	San Luis Potos
Mexico	Clinical Research Institute S.C.	Tlalnepantla	Estado De Mexico
Poland	Szpital Uniwersytecki nr 2 im.dr J. Biziela Dept of Clinical Reumatology	Bydgoszcz
Poland	Centrum Kliniczno - Badawcze J. Brzezicki, B. Górnikiewicz-Brzezicka Lekarze Spólka Partnerska	Elblag
Poland	Centrum Medyczne Pratia Gdynia ProFamilia Spolka Akcyjna, Oddzial w Gdyni	Gdynia
Poland	Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna	Lodz
Poland	Ai Centrum Medyczne Sp. Z O.O. Sp.K.	Poznan
Poland	RCMed	Sochaczew
Poland	Slaskie Centrum Reumatologii,Rehabilitacji i Zapobiegania Niepelnosprawnosci im. Gen. Jerzego Zietka	Ustron
Poland	Niepubliczny Zaklad Opieki Zdrowotnej "Biogenes" Sp. z o.o.	Wroclaw
Romania	Spitalul Clinic Judetean de Urgenta Brasov Sectia Reumatologie	Brasov
Romania	Spitalul Clinic Judetean de Urgenta Cluj Napoca Sectia Reumatologie	Cluj-napoca
Romania	Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Galati Sectia Reumatologie	Galati
Romania	RK Medcenter SRL	Iasi
Romania	Spitalul Municipal Ploiesti Sectia Reumatologie	Ploiesti
Russian Federation	SBIH of Nizhniy Novgorod region " City Clinical Hospital # 5"	Nizhny Novgorod
Russian Federation	Research Institute of Emergency Medical Care	Saint Petersburg
Russian Federation	SPb SBIH "Clinical Rheumatological Hospital # 25"	Saint Petersburg
Russian Federation	SHI Ulyanovsk Reg Clinical Hospital	Ul'yanovsk
Russian Federation	SBHI of Yaroslavl Region "Clinical Hospital #3"	Yaroslavl
Serbia	Institute of Rheumatology	Belgrade
Serbia	Special Hospital for Rheumatic Diseases	Novi Sad
Spain	Hospital de Cruces	Baracaldo
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada
Spain	Corporacio Sanitaria Parc Tauli	Sabadell
Spain	Hospital Infanta Luisa	Sevilla
United Kingdom	Princess Alexandra Hospital; Dept of Rheumatology; Williams Day Unit	Harlow	Essex
United Kingdom	Royal Free Hospital	London
United States	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Austin Regional Clinic, P.A.	Austin	Texas
United States	Tekton Research, Inc.	Austin	Texas
United States	Arthritis & Rheumatic Disease Specialties	Aventura	Florida
United States	RASF - Clinical Research Center	Boca Raton	Florida
United States	Joao Nascimento (Private Practice)	Bridgeport	Connecticut
United States	Medvin Clinical Research	Covina	California
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Arthritis and Rheumatology Consultants	Edina	Minnesota
United States	Center for Arthritis & Osteoporosis	Elizabethtown	Kentucky
United States	Medication Management, LLC	Greensboro	North Carolina
United States	MD Med Corp	Hemet	California
United States	Talbert Medical Group	Huntington Beach	California
United States	Montefiore Medical Center PRIME	Lake Success	New York
United States	Physician Research Collaboration	Lincoln	Nebraska
United States	Marietta Rheumatology Associates, PC	Marietta	Georgia
United States	Ramesh C Gupta, MD	Memphis	Tennessee
United States	Arizona Arthritis & Rheumatology	Mesa	Arizona
United States	QPS MRA (Miami Research Associates)	Miami	Florida
United States	Sentara Medical Group Clinical Research	Norfolk	Virginia
United States	Low Country Rheumatology, PA	North Charleston	South Carolina
United States	Omega Research Consultants Orlando	Orlando	Florida
United States	Family Clinical Trials, LLC.	Pembroke Pines	Florida
United States	Sun Valley Arthritis Center Ltd.	Peoria	Arizona
United States	West Broward Rheumatology Associates, Inc.	Tamarac	Florida
United States	BayCare Medical Group, Inc	Tampa	Florida
United States	McIlwain Medical Group, PA	Tampa	Florida
United States	Lovelace Scientific Resources, Inc.	Venice	Florida
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sandoz	Hexal AG

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Hungary,  Italy,  Malaysia,  Mexico,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira	Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value >5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value < 2.6 corresponds to remission DAS28-CRP = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * GDA or GH + 0.96 where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm	Study period 1: week 12
Secondary	Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira	Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value >5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value < 2.6 corresponds to remission DAS28-CRP = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * GDA or GH + 0.96 where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm	Study period 1: week 24
Secondary	Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission	Proportion of patients achieving European League against Rheumatism (EULAR) remission (defined as DAS28 CRP < 2.6 )	week 4, week 12 and week 24
Secondary	Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response	Proportion of patients achieving European League against Rheumatism (EULAR) good response (defined as DAS28<=3.2 at post-baseline assessment timepoint(s) with an improvement of >1.2 in DAS28 from baseline.)	week 4, week 12 and week 24
Secondary	Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response	Proportion of patients achieving European League against Rheumatism (EULAR) moderate response (defined as DAS28<=3.2 at post-baseline assessment timepoint(s) with an improvement of >0.6 to <=1.2 from baseline or DAS28 >3.2 to <=5.1 with an improvement of >0.6 to <=1.2 or of >1.2 from baseline or DAS28 >5.1 with an improvement of >1.2 from baseline) ;	week 4, week 12 and week 24
Secondary	Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria	Proportion of patients achieving EULAR/American College of Rheumatology (EULAR/ACR) Boolean remission criteria (defined as number of tender joint count 28 <=1 and swollen joint count 28 <=1, CRP level (mg/dL) <=1 and patient's global assessment <=1 on a scale of 1-10 (corresponding to <=10 on a scale of 1-100).	week 4, week 12, week 24
Secondary	Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira	DAS28-CRP is a disease activity score and defined in primary outcome measure. DAS28-ESR is the DAS28 erythrocyte sedimentation rate score.; DAS28-CRP and DAS28-ESR: best is 0,; < 2.6 - remission,; = 2.6 to = 3.2 - low disease activity; > 3.2 to = 5.1 - moderate disease activity; > 5.1 - high disease activity; DAS28-ESR = 0.56 * sqrt(tender28) + 0.28*sqrt(swollen28) + 0.7 * ln(ESR) + 0.014 * GDA where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • ESR is erythrocyte sedimentation rate (mm/h) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm.Values range from 0 to 10. Higher values mean a higher disease activity.	study period 1: week 2, 4, 24
Secondary	Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24	ACR20 response was defined if a patient fulfilled all 3 criteria below: -at least 20% improvement in tender 68 joint count; -at least 20% improvement in swollen 66 joint-count; And at least 20% improvement in at least 3 of the following 5 measures: - Patient's assessment of RA pain (visual analogue scale (VAS) 100 mm), -Patient's global assessment of disease activity (VAS 100 mm), -Physician's global assessment of disease activity (VAS 100 mm), -Patient self-assessed disability index(HAQ-DI© score), -Acute phase reactant (CRP or ESR). ACR50 and ACR70 responses were defined as ACR20 response replacing "20% improvement" by "50% improvement" and "70% improvement", respectively.	Week 4, week 12 and week 24
Secondary	Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24;	Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst).The HAQ© was scored in accordance with the recommendation from the developers outlined in the "HAQ PACK" from Stanford University, California.; Ramey Dr, Fries JF, Singh G. in B. Spilker Quality of Life and Pharmacoleconomics in Clinical Trials, 2nd ed, The Health Assessment Questionnaire 1995 -- Status and Review. Philadelphia: Lippincott-Raven Pub., 1996, p 227 - 237.; Fries JF, Spitz P, Kraines G, Holman H. Measurement of Patient Outcome in Arthritis, Arthritis and Rheumatism, 1980, 23:137-145.	Weeks 4, 12 and 24;
Secondary	Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (= 0.5) at Weeks 4, 12 and 24;	Health assessment questionnaire disability index (HAQ-DI©) ranges from 0 (best) to 3 (worst)	Weeks 4, 12 and 24;
Secondary	Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24	Health assessment questionnaire (HAQ-DI©) disability index ranges from 0 (best) to 3 (worst)	Weeks 4, 12 and 24;
Secondary	Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline)	FACIT© fatigue scale is a 13- item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function, ranging from 0 (worst) to 52 (best).	Weeks 4, 12 and 24;
Secondary	Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24	Outcome measure 13 presents changes in CRP measures in blood while Outome measure 7 presents changes in DAS28-CRP scores (calculated composite score to measure the disease activity)	Week 4, week 12, week 24
Secondary	Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24	Outcome measure 13 presents changes in ESR measures in blood while outcome measure 7 presents changes in DAS28-ESR scores (calculated composite score to measure the disease activity)	Week 4, week 12, week 24
Secondary	Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira	Incidence of injection site reactions in GP2017 and Humira	Treatment Period 1, 24 weeks
Secondary	Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients)	Frequency of patients having anti-drug antibody (ADA) during 24 weeks	baseline, week 2, week 4, week 12, week 24
Secondary	Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients)	Frequency of patients having anti-drug antibody (ADA) during 24 weeks	week 24, week 36, week 48
Secondary	Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira		week 48
Secondary	Study Period 2 - Health Assessment Questionnaire-Disability Index (HAQ-DI©) Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira	Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst)	Weeks 48
Secondary	Study Period 2 :Proportion of Patients Treated Continuously With GP2017 and Patients Treated With GP2017 After Switch From Humira Achieving HAQ-DI© Score in Normal Range =0.5 at Week 48		week 48
Secondary	Study Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira	FACIT©: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue	week 48
Secondary	Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira	DAS28-CRP is a disease activity score and defined in primary outcome measure. DAS28-ESR is the DAS28 erythrocyte sedimentation rate score.; DAS28-CRP and DAS28-ESR: best is 0,; < 2.6 - remission,; = 2.6 to = 3.2 - low disease activity; > 3.2 to = 5.1 - moderate disease activity; > 5.1 - high disease activity; DAS28-ESR = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.7 * ln(ESR) + 0.014 * GDA where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • ESR is erythrocyte sedimentation rate (mm/h) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm.Values range from 0 to 10. Higher values mean a higher disease activity.	week 48
Secondary	Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira	Incidence of injection site reactions	up to 48 weeks