Study evaluating long-term safety in adults with rheumatoid arthritis and in children and adolescents with childhood arthritis

• Register: EUCTR
• Last refreshed on: 20 March 2012
• Main ID: EUCTR2012-001145-40-Outside-EU/EEA
• Date of registration: 07/03/2012
• Prospective Registration: Yes
• Primary sponsor: Amgen, Inc. One Amgen Center Drive Thousand Oaks, California 91320
• Public title: Study evaluating long-term safety in adults with rheumatoid arthritis and in children and adolescents with childhood arthritis
• Scientific title: Open-label Extension Treatment with TNFR:Fc for Participating Patients in TNFR:Fc Clinical Trials
• Target sample size: 783
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001145-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Canada, United States

Contacts

• Name: Amgen Medical Information
• Affiliation: Amgen

• Name: Amgen Medical Information
• Affiliation: Amgen

Key inclusion & exclusion criteria

Inclusion criteria:
• Previous enrollment in etanercept protocols
• No clinically significant adverse events thought to be due to etanercept during previous treatment.
• Negative serum pregnancy test not more than 14 days before first dose of etanercept in women of childbearing protential (except for those who were surgically sterile, postmenopausal for at least 5 years, or prepubescent and not expected to reach sexual maturity for at least 1 year). Subjects who enrolled from a previous study coul have had the pregnancy test performed during the screening visit/Day 1.
• No more than 1 NSAID at a dose greater than the maximum recommended dose from the package insert (this dose had to be stable for at least 2 weeks before administration of etanercept).
• Maximum dose of 10 mg/day prednisolone or its equivalent (pediatric subjects from study 16.0016 could have received corticosteroids at a dose = 0.2 mg/kg, with a maximum dose of 10 mg/day. Corticosteroid doses had to be stable for at least 2 weeks before administration of etanercept).
• Heterosexually active men and women of childbearing potential had to agree to use medically accepted contraception (oral or subcutaneous contraceptives, intrauterine device, or condoms with spermicide) throughout the study, including during the screening/DMARD washout period, if applicable, and during the follow-up period.
• SGOT and SGPT = 2X ULN; serum bilirubin = 2X ULN (pediatric subjects [Study 16.0016]); hemoglobin stable at = 8.5 g/dl; platelet count = 100,000/cmm; white blood cell count = 3,500 cells/cmm; and serum creatinine = 2 mg/dL.
• Abel to self-inject or had a designee who could provide assistance.
• Capable of understanding and giving written, voluntary informed consent or had a parent/guasdian who could do so on the subject’s behalf.


Are the trial subjects under 18? yes
Number of subjects for this age range: 58
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 583
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 131

Exclusion criteria:
• Previous receipt of TNFR:Fc (p55), antibody ot TNF, anti-CD4 antibody, or diphtheria IL-2 fusion protein (DAB-IL-2)
• Receipt of investigational drugs or biologics (other than etanercept) within 1 month before the first dose of etanercept in this study.
• Receipt of DMARDS (eg: hydroxychloroquine, oral or injectable gold, azathioprine, cyclosporine, D-penicillamine, or sulfasalazine) within 2 weeks before the first dose of etanercept in this study.
• Receipt of methotrexate (MTX) within 2 weeks before the first dose of etanercept in this study, except for subjects from study 16.0014 on combination MTX and etanercept.
• Receipt of cyclosporine within 6 months before the first dose of etanercept in this study.
• Pregnant or breast feeding
• Significant concurrent diseases or change in medical condition since enrollment in previous etanercept studies including uncompensated congestive heart failure, myocardial infarction within 12 months of the first dose of etanercept in this study, unstable or stable angina pectoris, uncontrolled hypertension, devere pulmonary disease (requiring medical or oxygen therapy), history of cancer (other than resected cutaneous basal and squamous cell carcinoma, and in-situ cervical cancer) within 5 years of the first dose of etanercept in this study, diabetes mellitus requiring insulin therapy, known HIV seropositivity, known hepatitis B or C seropositivity, psoriasis (subjects on combination MTX and etanercept from study 16.0014), any conditionthe would cause this study to be detrimental to the subject as judged by the subject’s physician. Individual cases in which the subject’s physician was uncertain about enrolling the subject into the study were to be discussed with the medical monitor.
• Current or past psychiatric disease that could have interfered with ability to comply with the study or informed consent,
• History of alcohol or drug abuse that would have interfered with compliance to the study protocol.
• Subjects on combination MTX and etanercept treatment from study 16.0014 who were unwilling to limit alcohol consumption to less than 2 drinks per week (1 drink equals 12 ounces of beer, 1 ounce of hard liquor, or 4 ounces of wine).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis (RA) in adults and juvenile idiopathic arthritis (JIA) for subjects who did not respond to conventional DMARDS

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Enbrel
Product Name: Enbrel (Etanercept)
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Enbrel
Product Name: Enbrel (Etanercept)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): Efficacy:
For adults, ACR 20 and for pediatric subjects, the Juvenile Arthritis Definition of Improvement (JA-DOI).
Safety:
For adults and pediatric subjects the primary safety endpoint was adverse events through year 1 and serious adverse event rates throughout the study.

Secondary Objective: The secondary objective of the cumulative dataset was to describe the demography, subject exposure to investigational product, study discontinuations over time, and long-term effectiveness of etanercept in subjects with DMARD-refractory RA or JIA.

The secondary objective of the study-specific data set was to evaluate long term biological activity of etanercept in various subject populations with RA or JIA.

Timepoint(s) of evaluation of this end point: Monthly for first 2 months, then every 3 months for the rest of year 1, then every 6 months for rest of the study

Main Objective: The primary objective of the cumulative dataset (the cumulative dataset includes subject data from study 20021618 as well as data from the the initial Enbrel study) was to evaluate the long-term safety of etanercept in subjects with DMARD-refractory RA or JIA. The primary objectives of the study-specific dataset (the study-specific dataset includes subject data from study 20021618 only) were the following:
• Evaluate the long term safety of etanercept in various subject populations with RA or JIA
• Evaluate improvement in physical function/disability and quality of life.

Secondary Outcome(s)

Secondary end point(s): Efficacy: For Adults
• ACR 50 and 70 responses
• Duration of morning stiffness
• Disease activity score (DAS-28)
• C-reactive protein (CRP)
• Simple disease activity index (SDAI)
• Clinical disease activity index (CDAI)
• Complete response defined as 0 swollen joints and 0 tender joints
• Remission based on DAS-28 and CRP
• Change from baseline in ACR components
• Change from baseline in DAS-28, CRP, CDAI and SDAI.
• Change from baseline in morning stiffness
Efficacy: For Pediatric Subjects
• Juvenile arthritis definition of improvement (JA-DOI) 30%, 50%, 70%, 90% and 100%
• JA-DOI components, including physician global assessment (PGA), subject’s/parent’s global assessment (SGA), number of active joints, Childhood Health Assessment Questionnaire (CHAQ), CRP, loss of motion (LOM) joint count.
• LOM plus tender/painful joint count, subject’s pain VAS, articular severity score, duration of morning stiffness and complete response (0 swollen joints and 0 tender joints)
Safety endpoints for the cumulative dataset were:
• Exposure to etanercept
• Safety-related discontinuations
• Serious adverse events, including serious infectious events and deaths
• Other predefined events of interest (eg: malignancies, infections, cardiovascular events and demyelination events)
Safety endpoints for the study-specific dataset
• Exposure to etanercept
• Vital signs and physical exams
• All serious and non-serious adverse events
• Hematology profile
• Chemistry profile, including urinalysis
• Premature discontinuations
• Other predefined events of interest (eg: hospitalizations, deaths, serious infections, malignancies, and other connective tissue disease).

Timepoint(s) of evaluation of this end point: Monthly for first 2 months, then every 3 months for the rest of year 1, then every 6 months for rest of the study

Secondary ID(s)

NCT00357903

20021618

Source(s) of Monetary Support

Amgen, Inc.

Pfizer, Inc.