E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Axial Spondyloarthritis (AxSpA) |
|
E.1.1.1 | Medical condition in easily understood language |
Early ankylosing spondyloarthritis |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051265 |
E.1.2 | Term | Spondyloarthropathy |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the efficacy of ETN against placebo in improving symptoms of early non-radiographic axial SpA at 12 weeks when added to a background NSAID at the optimal anti-inflammatory dose. |
|
E.2.2 | Secondary objectives of the trial |
1. To assess the efficacy and safety of ETN + background NSAID over 104 weeks;
2. To compare the effect of ETN 50 mg once weekly versus placebo on inflammation seen in MRI of the spine at 12 weeks when added to a background NSAID at the optimal anti-inflammatory dose;
3. To compare the quality of life between those subjects treated with ETN 50 mg once weekly versus placebo over 12 weeks when added to a background NSAID at the optimal anti-inflammatory dose. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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.
Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study;
Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Diagnosis of axial spondyloarthritis, as defined by the ASAS criteria. Duration of symptoms.of >3 months and <5 years at the time of consent.
2. Active symptoms defined by a BASDAI ≥4 at the screening visit.
3. Axial symptoms of 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 failed at least 2 NSAIDs (including the current one) taken separately at the optimal tolerated dose with a total combined duration of >4 weeks.
4. Subject must be taking a stable dose of an NSAID for at least 14 days before baseline.
5. Female or male 18 years or older but less than 50 years at the time of consent.
6. In the opinion of the investigator, subject is a reasonable candidate for treatment with etanercept.
7. No contraindication to MRI examination (metal implants or inability to lay flat for 30-60 minutes for example).
8. Negative serum pregnancy test taken at screening, negative urine pregnancy test taken at baseline and negative serum pregnancy test collected at baseline.
9. Agreement by male subjects who are not surgically sterile and female subjects who are not surgically sterile or post menopausal to use a highly effective method of birth control for the duration of the study.
10. Ability to self-inject drug or have a designee who can do so.
11. Ability to store injectable test article under refrigerated conditions.
12. Demonstrates an adequate screening for tuberculosis (TB) in accordance with local country guideline.
13. Subject is able to complete health outcomes assessments and test article diary.
Main Inclusion Criteria Period 2
1. Successfully completed Period 1. |
|
E.4 | Principal exclusion criteria |
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.
2. Any previous treatment with a tumor necrosis factor-alpha (TNF-α) inhibitor, B/T cell inhibitor or other biologic or immunosuppressive agent for a condition other than IBD.
3. Subject is currently being treated or had previous treatment within 6 months for IBD with any tumor necrosis factor-alpha (TNF-α) inhibitor or any other immunosupressant.
4. Any orthopedic or medical condition that can cause chronic back pain (different than SpA) such as spondylodiscitis, tumor or advance discopathy.
5. Evidence of IBD flare within 6 months of baseline.
6. Evidence of current or recent episodes of uveitis within 6 months of baseline.
7. Radiological sacroiliitis grade is 3-4 unilaterally or grade 2 bilaterally as defined by the NY criteria. Only results from the central imaging reader will determine eligibility. Historical x-rays (obtained within 4 months of screening) may be utilized, however these subjects must exhibit radiological sacroilitis grade 0-1 unilaterally or grade 0 bilaterally.
8. Subject has a known or suspected allergy, hypersensitivity, or contraindication to ETN, its excipients, or other compounds related to this class of medication.
9. Subject has concurrent treatment with more than 1 NSAID within 14 days at baseline. 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.
10. Subject has had the dose of NSAID that changed within 14 days before baseline.
11. DMARDS other than methotrexate, sulfasalazine and hydroxychloroquine within 4 weeks of baseline.
12. Subject has had a dose of prednisone >10 mg/day (or equivalent) or has had a dose changed within 4 weeks before baseline.
13. Subject has received an intra-articular, intravenous, intramuscular, or subcutaneous (SC) corticosteroid within 4 weeks before baseline.
14. Subject is a pregnant or breastfeeding woman.
15. Has current or recent (within 2 years of screening) active TB infection.
Local country guidelines should be followed for appropriate TB screening in the setting of anti-TNF therapy, including a minimum of a chest radiograph and objective TB testing such as purified protein derivative [PPD] or Quantiferon depending on what is acceptable per local guidelines.
16. Untreated latent TB.
Subjects with known latent TB infection may be allowed only if local guidelines are followed for prophylactic therapy and if TB chemoprophylaxis has been adequately completed or initiated at least 4 weeks prior to screening.
17. Received TB chemoprophylaxis during screening and has had ALT and/or AST >2x upper limit of normal [ULN] during this period.
For subjects that have been diagnosed with TB and started chemoprophylaxis during the screening period, additional blood samples for ALT and AST must be drawn between 3- 4 weeks after initiating chemoprophylaxis. The results need to be reviewed prior to randomization.
18. Serious infection (infection associated with hospitalization and/or intravenous antibiotics) within 1 month before test article administration.
19. Active infection at the time of the screening visit and/or the baseline visit. Certain minor active infections (ie, vaginitis, tinea, etc) could be allowed on a case-by-case basis only after approval from the study physician clinician.
20. Participation in other studies with a therapeutic active component within 3 months before the current study begins and/or during study participation. (Participation in non-interventional or retrospective studies might be permitted following consultation with the Pfizer Clinical team.)
21. Planned elective surgery during Period 1.
22. Subject received any live vaccines (attenuated vaccines) within 4 weeks before baseline.
23. Subject is illiterate.
24. Subject has an abnormal hematology or blood chemistry profile during the screening period. Refer to Protocol for management of exclusionary lab values at baseline.
White blood cell (WBC) count ≤3.5 x 109/L;
Hemoglobin level ≤85 g/L or ≤5.3 mmol/L;
Hematocrit ≤27%;
Platelet count ≤125 x 109/L;
Serum creatinine level ≥175 μmol/L (≥1.98 mg/dL);
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥2 times the laboratory’s upper limit of normal.
25. Subject has any clinically relevant concurrent medical conditions (refer to Protocol for full list). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the proportion of subjects who achieve ASAS 40 at week 12. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 12 (End of Double Blind Treatment Period)
|
|
E.5.2 | Secondary end point(s) |
1. Proportion of subjects who achieve ASAS 40 at time points other than 12 weeks;
2. Proportion of subjects who achieve ASAS 20;
3. Proportion of subjects who achieve ASAS 5/6;
4. Changes from baseline in ASDAS;
5. Proportion of subjects with ASAS partial remission;
6. Time to ASAS partial remission;
7. Changes from baseline in Subject Assessment of Disease Activitiy (VAS);
8. Changes from baseline in the VAS Physician Global Assessment;
9. Changes from baseline in VAS nocturnal and total back pain over time;
10. Changes from baseline in the BASFI and its components;
11. Changes from baseline in the BASDAI and its components;
12. Proportion of subjects who achieved BASDAI 20 and BASDAI 50;
13. Changes in BAS-G;
14. Changes from baseline in spinal mobility as measured by BASMI (and its individual components), and occiput-to-wall distance, and chest expansion;
15. Changes in inflammation at week 12 as measured by MRI of the spine at week 12;
16. Changes from baseline in tender and swollen joint counts (44 count);
17. Changes from baseline on dactylitis and enthesitis score (MASES);
18. Changes from baseline in the acute phase reactants C Reactive Protein (CRP) and Erythrocyte sedimentation rate (ESR);
19. Health Outcomes Assessments using the following instruments: WPAI, HADS, EQ-5D MFI, SF 36, ASQoL, ASWIS, MOS Sleep, MFI, PASS, and MCII. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints are evaluated at all in clinic study visits (visit 1-16 or early discontinuation)
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Period 1 is controlled, Period 2 is Open-label |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Belgium |
Colombia |
Denmark |
Finland |
France |
Germany |
Hungary |
Italy |
Korea, Republic of |
Netherlands |
Spain |
Taiwan |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 25 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 25 |