Study Evaluation of the Long-Term Safety and Clinical Benefit of Etanercept In 3 Sub-types of Childhood Arthritis

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2010-023802-10-DE
• Date of registration: 09/08/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.235 East 42nd Street, New York, NY 10017
• Public title: Study Evaluation of the Long-Term Safety and Clinical Benefit of Etanercept In 3 Sub-types of Childhood Arthritis
• Scientific title: AN OPEN-LABEL EXTENSION STUDY TO ASSESS THE LONG-TERM SAFETY AND CLINICAL BENEFIT OF ETANERCEPT IN CHILDREN AND ADOLESCENTS WITH EXTENDED OLIGOARTICULAR JUVENILE IDIOPATHIC ARTHRITIS, ENTHESITIS-RELATED ARTHRITIS, OR PSORIATIC ARTHRITIS WHO WERE PREVIOUSLY ENROLLED IN PROTOCOL 0881A1-3338-WW(B1801014) - Clipper 2
• Date of first enrolment: 29/09/2011
• Target sample size: 123
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023802-10
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Colombia, Czech Republic, France, Germany, Hungary, Italy, Latvia, Lithuania, Mexico, Netherlands, Norway, Poland, Russian Federation, Serbia, Slovakia, Slovenia, Spain

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria for All Subjects at Baseline Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document (and assent document, as applicable) indicating that the subject (and/or a legal representative/guardian(s) as applicable according to subject age and local guidelines) has been informed of all pertinent aspects of the period of the study in which participation is being considered.
2. Subjects who are willing and able to comply with all applicable aspects of the period of the study in which participation is being considered, including scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Receipt of at least 1 dose of investigational product and participation for approximately 96 weeks in study 0881A1-3338.
4. The subject and/or the parent or legal representative/guardian of the subject must be able to provide contact information, including primary care physician or other treating physician.

Additional Inclusion Criteria for Subjects Planning to Continue Investigational Product in the Active Treatment Period Subjects must meet the following additional inclusion criteria at the baseline visit to be eligible to continue investigational product in study B1801023:
1. Have completed approximately 96 weeks of investigational product in study 0881A1-3338 and, in the investigator’s judgment, is appropriate to continue treatment with etanercept.
2. Either the subject or an available adult must be capable (according to the investigator’s judgment) of reconstituting and administering injections of subcutaneous (SC) etanercept.
3. The subject, parent, or legal representative/guardian of the subject must be able to read and complete the protocol-specified efficacy assessments.
4. The first dose of investigational product in study B1801023 must be administered within 6 weeks of receiving the last dose of investigational product in the study 0881A1-3338.

Additional Inclusion Criteria for Subjects Planning to Enter in the Withdrawal/Re-treatment Period
1. Evidence of a personally signed and dated informed consent document (and assent document, as applicable) indicating that the subject (and/or a legal representative/guardian(s) as applicable according to subject age and local guidelines) has been informed of all aspects of the withdrawal/re-treatment period of the study. Only one informed consent document/assent will be signed and dated for the withdrawal/re-treatment period.
2. The subject is willing and able to comply with all applicable aspects of the withdrawal/re-treatment period of the study, including scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. The subject and/or the parent or legal representative/guardian of the subject must be able to provide contact information, including primary care physician or other treating physician.
4. For subjects entering directly into the withdrawal/re-treatment period, have completed approximately 96 weeks of investigational product in study 0881A1-3338.
5. For subjects entering directly into the withdrawal/re-treatment period, the baseline visit in study B1801023 must be completed within 14 days of the last dose of investigational
Exclusion criteria:
Exclusion Criteria for All Subjects at Baseline

Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.

Additional Exclusion Criteria for Subjects Planning to Continue Investigational Product in the Active Treatment Period Subjects who completed approximately 96 weeks of investigational product in study 0881A1-3338 and present with any of the following will not be allowed to continue investigational product in study B1801023:
1. Withdrawal from investigational product in study 0881A1-3338 for any reason.
2. History of malignancy other than squamous cell, basal cell carcinoma or cervical carcinoma in situ.
3. Participation in other clinical studies of investigational drugs or investigational combinations of approved drugs between the week 96 visit in study 0881A1-3338 and the baseline visit in study B1801023 or during participation in the active treatment period of study B1801023.
4. Pregnant or breastfeeding female subjects.
5. Receipt of any of the following between the week 96 visit in study 0881A1-3338 and the baseline visit in study B1801023:
• Any immunosuppressive biologic drugs, including but not limited to TNF inhibitors (other than etanercept), abatacept, rituximab, anakinra and tocilizumab;
• Immunosuppressive drugs (excluding corticosteroids) (eg, cyclophosphamide, cyclosporine, azathioprine);
• Leflunomide;
• Use of more than 1 of the non-biologic DMARDs permitted in study 0881A1-3338 (ie, methotrexate, hydroxychloroquine, chloroquine, sulfasalazine) in subjects <18 years of age;
• Use of more than 2 of the non-biologic DMARDs permitted in study 0881A1-3338 (ie, methotrexate, hydroxychloroquine, chloroquine, sulfasalazine) or hydroxychloroquine and chloroquine taken at the same time in subjects =18 years of age;
• Non-biologic DMARDs other than those permitted in study 0881A1-3338 (ie, methotrexate, hydroxychloroquine, chloroquine, sulfasalazine), or those not listed under other exclusion criteria;
• Any live (attenuated) vaccines. 6. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
7. Signs and symptoms or suspicion of active tuberculosis.

Additional Exclusion Criteria for Subjects Planning to Enter in the Withdrawal/Re-treatment Period
1. Withdrawal from investigational product in study 0881A1-3338 for any reason.
2. Prior and/or current participation in the observational period of study B1801023.
3. Prior and/or current participation in the withdrawal/re-treatment period of study B1801023.

Additional Exclusion Criteria for Subjects Planning to Restart Investigational Product in the Re-treatment Period Please refer to Protocol for more detail.


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

Health Condition(s) or Problem(s) studied

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

OLIGOARTICULAR JUVENILE IDIOPATHIC ARTHRITIS, ENTHESITIS RELATED ARTHRITIS, OR PSORIATIC ARTHRITIS
MedDRA version: 20.0 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Enbrel®
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: ETANERCEPT
CAS Number: 185243690
Current Sponsor code: B1801023
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Enbrel®
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ETANERCEPT
CAS Number: 185243690
Current Sponsor code: B1801023
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: To monitor the occurrence of malignancy in pediatric subjects with extended oligoarticular JIA, ERA, or PsA.

Primary end point(s): Occurrence of malignancy.

Timepoint(s) of evaluation of this end point: at minimum every 2 years

Secondary Objective: • To assess the long-term safety profile of etanercept;
• To evaluate the long-term effect of etanercept on clinical benefit and physical function.

Exploratory Objectives
• To evaluate clinical benefit and physical function after withdrawal of etanercept;
• To evaluate effect of etanercept on clinical benefit and physical function after disease relapse.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At minimum every 2 years

Secondary end point(s): Secondary Endpoints for Subjects in the Observational Period
• Occurrence of serious adverse events, including serious infections;
• Occurrence of medically important infections (ie, an infection requiring hospitalization and /or parenteral [intravenous (IV), intra-muscular (IM)] anti-infective agents).

Secondary Endpoints for Subjects in the Active Treatment Period, and Withdrawal/Re-treatment Period
• Occurrence of serious adverse events, including serious infections;
• Occurrence of medically important infections (ie, an infection requiring hospitalization and /or parenteral [intravenous (IV), intra-muscular (IM)] anti-infective agents);
• Occurrence of all adverse events, including infections, infections considered preventable by vaccination, and injection site reactions;
• Occurrence of withdrawals from investigational product due to adverse events;
• Laboratory evaluations;
• Growth parameters;
• Tanner Stage Assessment for selected subjects;
• ACR Pediatric 30, 50, 70, 90, and 100, defined as = 30% (and 50%, 70%, 90%, 100%, respectively) improvement from baseline in at least 3 of the 6 following variables, with no more than 1 of the remaining variables worsening by > 30 %:
• Physician’s Global Assessment (PGA) of Disease Activity on a 21-circle visual analogue scale (VAS);
• Patient/Parent Global Assessment on a 21-circle VAS;
• Childhood Health Assessment Questionnaire (CHAQ)/Health Assessment Questionnaire (HAQ);
• Number of joints with active arthritis, defined as joints that are swollen or, in the absence of swelling, joints with limited range of motion accompanied by pain and/or tenderness;
• Number of joints with limited range of motion;
• Laboratory measure of inflammation, c-reactive protein (CRP);
• Individual components of the ACR Pediatric Assessments;
• Pain Assessment on a 21-circle VAS;
• Duration of morning stiffness in minutes;
• Clinically inactive disease defined as follows per Wallace Criteria:
• No joints with active arthritis (defined as joints that are swollen or, in the absence of swelling, joints with limited range of motion accompanied by pain and/or tenderness);
• No fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA;
• No active uveitis;
• CRP level within normal limits in the laboratory where tested or, if elevated, not attributable to JIA;
• PGA of disease activity score of best possible on the scale used;
• Duration of morning stiffness of = 15 minutes;
• The Juvenile Arthritis Disease Activity Score (JADAS), using 4 components (PGA of Disease Activity, Patient/Parent Global Assessment, number of joints with active arthritis and CRP).

Additional Secondary Endpoints for ERA Subjects
• Overall Back Pain and Nocturnal Back Pain on a 100 mm VAS;
• Bath Ankylosing Spondylitis Metrology Index (BASMI) and its components (Intermalleolar Distance, Cervical Rotation, Modified Schober’s Test, Lateral Flexion, and Tragus to Wall Distance).

Additional Secondary Endpoints for PsA Subjects
• Body Surface Area (BSA);
• PGA of Psoriasis.

Secondary ID(s)

B1801023

2010-023802-10-HU

Source(s) of Monetary Support

Pfizer Inc.

Ethics review

Status: Approved
Approval date: 31/08/2011
Contact: