A Multicenter Open-Label Study of Etanercept Withdrawal and Retreatment in Subjects with Non-Radiographic Axial Spondyloarthritis who Achieved Adequate 24 Week Response

• Register: EUCTR
• Last refreshed on: 25 May 2020
• Main ID: EUCTR2015-000541-24-PL
• Date of registration: 16/09/2015
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A Multicenter Open-Label Study of Etanercept Withdrawal and Retreatment in Subjects with Non-Radiographic Axial Spondyloarthritis who Achieved Adequate 24 Week Response
• Scientific title: A Multicenter Open-Label Study of Etanercept Withdrawal and Retreatment in Subjects with Non-Radiographic Axial Spondyloarthritis who Achieved Adequate 24 Week Response
• Date of first enrolment: 30/09/2015
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000541-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; 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; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Australia, Belgium, Bulgaria, Colombia, Czech Republic, Finland, France, Germany, Hungary, Korea, Democratic People's Republic of, Netherlands, Poland, Romania, Spain, Sweden, Taiwan, United States

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:
Period 1
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the entire study and for 28 days after the last study visit.
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure; or
Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state
4. Duration of symptoms of =3 months and <5 years at the time of consent.
5. Diagnosis of ax SpA as defined by the ASAS criteria
The ASAS criteria state that subjects have to have =3 months of back pain and
age of onset <45 years, and:
• Sacroiliitis on imaging plus 1 SpA feature
OR
• Positive Human Leucocyte Antigen B27 (HLA-B27) plus 2 SpA features.
Sacroiliitis on imaging is defined as either:
• Active inflammation on MRI highly suggestive of sacroiliitis associated with SpA
OR
• Defined radiographic sacroiliitis according to the Modified NY criteria**
**Subjects in this study cannot meet the criteria based on the second bullet (since defined radiographic sacroiliitis is an exclusion criterion). In order to meet the imaging criteria for ASAS, subjects must have positive sacroiliitis on MRI based on readings performed by the central imaging vendor. This criterion cannot be based on local MRI evaluation or historical MRIs.
If a subject has negative sacroiliitis on MRI, then they must have positive HLA-B27 plus 2 SpA features. Conversely, if a subject is HLA-B27 negative, then they must have positive sacroiliitis on MRI and at least 1 SpA feature.
The SpA features are listed below;
• Inflammatory back pain;
• Arthritis;
• Enthesitis (heel);
• Uveitis;
• Dactylitis;
• Psoriasis;
• Crohn’s/ Colitis;
• Good response to NSAIDs;
• Family history of SpA;
• HLA-B27;
• Elevated hsCRP.
6. Subjects must have positive MRI findings (active inflammation on MRI highly suggestive of sacroiliitis associated with SpA) and/or positive hsCRP (defined as hsCRP >3 mg/l).
7. Active symptoms defined by an ASDAS CRP greater than or equal to 2.1 at the
screening visit.
8. Back pain with a less than favorable response to current intake of an NSAID at the optimal tolerated dose as determined by the investigator. Subjects must have experienced less than favorable response to at least 2 NSAIDs (including the current one) taken separately at the optimal tolerated dose with a total combined duration of >4 weeks.
9. Subject must be taking a stable dose of an NSAID for at least 14 days before the first dose.
10. Female or male 18 years or older (20 or older if required by local regulations) but less than 50 at the time of consent.
11. In the opinion of the investigator, subject is reasonable candidate for treatment with ETN.
12. No contraindication to MRI examination (metal implants or inability to lie flat for 30-60 minutes for example).
13. Negative serum pregnancy test performed at screening, negative urine pregnancy test performed prior to the first d
Exclusion criteria:
1. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
2. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks before the current study begins and/or during study participation. Participation in studies involving investigational drug greater than 4 weeks to one year before the current study begins will be permitted on a case-by-case basis.
3. Radiological sacroiliitis Grades 3-4 unilaterally or Grade =2 bilaterally as defined by the NY criteria. Only results from the central imaging reader will determine eligibility. In all countries except Germany: Historical x-rays (obtained
within 4 months of screening) may be utilized, however these subjects must exhibit radiological sacroiliitis Grade 0-1 unilaterally or Grade 0 bilaterally.
4. Any previous treatment with a tumor necrosis factor-alpha (TNF-?) inhibitor, B/T cell inhibitor or other biologic or immunosuppressive agent for a condition other than IBD.
5. Subject is currently being treated or had previous treatment within 6 months for IBD with any tumor necrosis factor-alpha (TNF-?) inhibitor or any other immunosuppressant.
6. Evidence of IBD flare within 6 months of first dose.
7. Evidence of active uveitis within 6 months of first dose.
8. Any current or past orthopedic or medical condition that in the opinion of the investigator could cause chronic back pain.
9. Subject has known or suspected allergy, hypersensitivity, or contraindication to ETN, its excipients, or other compounds, related to this class of medication.
10. Subject has concurrent treatment with more than 1 NSAID within 14 days at first dose. Aspirin use, at daily doses up to 325 mg if indicated for cardiovascular protection is permissible and will not be counted as an additional NSAID.
11. Disease modifying anti-rheumatic drugs (DMARDs) other than methotrexate (MTX), sulfasalazine and hydroxychloroquine taken within 4 weeks of first dose. Subjects may be taking only one allowable DMARD at a time.
12. Subject has had an oral dose of prednisone >10 mg/day (or equivalent) or has had a dose change within 4 weeks of first dose.
13. Subject has received an intra-articular, intravenous, intramuscular, or subcutaneous (SC) corticosteroid within 4 weeks of first dose.
14. Subject has current or recent (within 2 years of screening) active TB infection.
• Subjects with remote history (more than 2 years before screening) of active TB are allowed if clear documentation of completion of adequate treatment (as
defined by local guidelines) exists.
• Local country guidelines should be observed for appropriate TB screening in the setting of anti-TNF therapy, including a minimum of a chest radiograph and
objective TB testing such as a purified protein derivative (PPD) or Quantiferon
depending on what is acceptable per local guidelines.
15. Subject has untreated latent TB. (Subjects with known latent TB may be allowed only if local guidelines are followed for therapy and if treatment for latent TB has been adequately completed or initiated at least 4 weeks prior to screening.)
16. Subject has received treatment for latent TB during screening and has had alanine aminotranferase (ALT) and/or aspartate aminotranferase (AST) =2 times the upper limit of normal (ULN) during this period.
• Fo

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

Health Condition(s) or Problem(s) studied

Spondyloarthritis (SpA)
MedDRA version: 21.1 Level: PT Classification code 10071400 Term: Axial spondyloarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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

Intervention(s)

Trade Name: Enbrel (Etanercept)
Product Name: Enbrel (Etanercept)
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Etanercept
CAS Number: 185243-69-0
Current Sponsor code: PF-05208752
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: • To estimate the proportion of subjects who flare within 40 weeks following withdrawal of ETN in subjects who have achieved ASDAS CRP less than 1.3 (inactive disease).

Primary end point(s): • The primary endpoint is the occurrence of flare (defined as an ASDAS ESR greater than or equal to 2.1) within 40 weeks following withdrawal of ETN.

Secondary Objective: • To estimate time to flare after withdrawal of ETN, and to compare it to that in patients from B1801031 who continued ETN therapy.
• To estimate the efficacy of 12 weeks of retreatment in subjects who experience a flare after withdrawal of ETN.
• To estimate the efficacy of ETN over 24 weeks of initial treatment.
• To estimate the safety and tolerability of ETN in this population.

Timepoint(s) of evaluation of this end point: 40 weeks

Secondary Outcome(s)

Secondary end point(s): The following key secondary endpoint will be estimated:
• The time to flare following withdrawal of ETN (as measured from treatment withdrawal until ASDAS ESR greater than or equal to 2.1).
The following secondary endpoints and outcome measures will be estimated within 40 weeks following withdrawal of ETN and during the 12 week re-treatment period (if applicable):
• Occurrence of ASDAS CRP less than 1.3 (inactive disease);
• Occurrence of ASAS 20 and ASAS 40;
• Occurrence of ASAS partial remission;
• ASDAS;
• Occurrence of ASDAS major improvement and clinically important improvement;
• Nocturnal and total back pain;
• Bath Ankylosing Spondylitis Functional Index (BASFI) and its components;
• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and its components;
• Occurrence of BASDAI 50;
• High sensitivity C Reactive Protein (hsCRP);
• Health Outcomes Assessments using the following instruments: EuroQoL-5D Health Questionnaire (EQ-5D), SF-36 and Work Productivity and Activity Impairment (WPAI);
• MRI SIJ/spine as measured by Spondyloarthritis Research Consortium of Canada (SPARCC).
The following secondary endpoint will be estimated over 12 weeks following re-treatment of patients who flare:
• Time to ASDAS inactive disease after re-treatment.
Other endpoints:
• Subject Assessment of Disease Activity (SADA);
• Physician Global Assessment (PGA);
• Bath Ankylosing Spondylitis Patient Global Assessment Score (BAS-G);
• Tender and swollen joint counts (44 count);
• Dactylitis and enthesitis score (Maastricht Anklyosing Spondylitis Enthesitis Score [MASES]).

Timepoint(s) of evaluation of this end point: Various timepoints

Secondary ID(s)

2015-000541-24-DE

B1801381

Source(s) of Monetary Support

Pfizer Inc., 235 East 42nd Street, New York, NY 10017

Ethics review

Status: Approved
Approval date: 08/09/2015
Contact:

Results

• Results available: Yes
• Date Posted: 23/05/2020
• Date Completed: 06/09/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000541-24/results