| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Peripheral Spondyloarthritis |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10052775 |
| E.1.2 | Term | Spondyloarthropathies |
|
| 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 objective of this study is to evaluate the efficacy and safety of adalimumab
40 mg given every other week (eow) subcutaneously (SC) compared to placebo for 12 weeks followed by open-label safety and efficacy assessments in subjects with non-AS, non-PsA active peripheral spondyloarthritis who have had an inadequate response to ≥ 2 NSAIDs, or are intolerant to or have a contraindication for NSAIDs. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is ≥ 18 years of age.
2. Subject must have had, as defined by the Investigator, an inadequate response to
≥ 2 NSAIDs, or are intolerant to or have a contraindication for NSAIDs.
3. Subjects must have current arthritis (asymmetric or predominantly in the lower
limbs) or enthesitis (except for enthesitis only along the spine, sacroiliac joints
and/or chest wall) or dactylitis PLUS:
● At least one of the following SpA features
o Anterior uveitis confirmed by an ophthalmologist (past or present)
o Crohn's disease or ulcerative colitis diagnosed by a physician (past or
present)
o Evidence of preceding infection (acute diarrhea or non-gonococcal
urethritis or cervicitis 1 month before arthritis)
o HLA-B27 positivity
o Sacroiliitis on imaging; based on prior MRI (refer to Section 1.3 for
definition)
OR
● At least two of the following SpA features:
o Arthritis (past or present diagnosis), adequately documented and
identified, or diagnosed by a qualified medical professional
o Enthesitis (any location, past or present diagnosis), adequately
documented and identified, or diagnosed by a qualified medical
professional
o Dactylitis (past or present diagnosis) adequately documented and
identified, or diagnosed by a qualified medical professional
o Inflammatory Back Pain (past or present) (refer to Section 1.3 for
definition)
o Family history for SpA (refer to Section 1.3 for definition)
4. Subjects must have at Screening and Baseline Visit any one of the following:
● ≥ 2 tender joints and ≥ 2 swollen joints, (asymmetric or predominantly in the
lower limbs)
OR
● at least 1 joint with active inflammatory arthritis, not associated with
dactylitis, plus
○ ≥ 2 enthesitis sites (except for enthesitis only along the spine, sacroiliac
joints and/or chest wall)
OR
○ ≥ 2 digits with dactylitis;
5. Subject must have had onset of peripheral SpA symptoms ≥ 3 months prior to the
Baseline Visit.
6. Subjects must have baseline disease activity as defined by Patient Global
Assessment of Disease Activity VAS ≥ 40 mm and Patient Global Assessment of
Pain VAS ≥ 40 mm at Screening and Baseline Visits.
7. In subjects with concurrent axial SpA symptoms, the peripheral SpA symptoms
must be the predominant symptoms at study entry based on the Investigator's
clinical judgment.
8. If female, subject is either not of childbearing potential, defined as postmenopausal
for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral
oophorectomy or hysterectomy) or is of childbearing potential and is practicing an
approved method of birth control throughout the study and for 150 days after last
dose of study drug.
Examples of approved methods of birth control include the following:
● Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD);
● Oral, parenteral or intravaginal contraceptives for 90 days prior to study drug
administration;
● A vasectomized partner.
9. Subject is judged to be in good health as determined by the Principal Investigator
based upon the results of medical history, laboratory profile, physical examination,
chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during
Screening.
10. Subject has a negative PPD test (or equivalent) and CXR (PA and lateral view) at
Screening. If the subject has a positive PPD test (or equivalent), has had a past
ulcerative reaction to PPD placement and/or a CXR consistent with prior
TB exposure, the subject must initiate, or have documented completion of a course
of anti-TB therapy; (Section 5.3.1).
11. Subjects must be able and willing to provide written informed consent and comply
with the requirements of this study protocol.
12. Subjects must be able and willing to self-administer SC injections or have a
qualified person available to administer SC injections. |
|
| E.4 | Principal exclusion criteria |
1. History of a diagnosis of psoriasis or psoriatic arthritis.
2. Subject fulfilling a diagnosis of ankylosing spondylitis (as defined by the modified
New York criteria; Appendix C) at or prior to the Screening Visit.
3. Presence of back pain ≥ 20 mm on a Total Back Pain VAS at Screening or
Baseline.
4. Subject with extra-articular manifestation (e.g., inflammatory bowel disease,
uveitis, etc.) that is not clinically stable for at least 28 days prior to baseline.
5. Medical history of inflammatory arthritis of a different etiology other than
peripheral spondyloarthritis (e.g., rheumatoid arthritis, systemic lupus
erythematosus, gout, or any arthritis with onset prior to age 16 years such as JIA).
6. Prior exposure to any biologic therapy with a potential therapeutic impact on SpA,
including anti-TNF therapy.
7. Subject has received cyclosporine or other second line anti-rheumatic therapy
(except MTX, SSZ, azathioprine or hydroxychloroquine) within 28 days prior to
the Baseline Visit.
8. If entering the study on concomitant DMARDs at Screening/Baseline, subject not
on stable dose of MTX (≤ 25 mg per week) and/or SSZ (≤ 3 g per day) and/or
hydroxychloroquine (≤ 400 mg per day) for 28 days prior to the Baseline Visit.
9. If entering the study on concomitant azathioprine, subject not on stable dose
(≤ 150 mg/day) for 28 days prior to the Baseline Visit or on azathioprine and
another concomitant immunosuppressive drug at study entry.
10. If entering the study on concomitant NSAIDs and/or analgesics, subject on opioid
analgesics (other than tramadol) or subject not on stable doses for 14 days prior to
baseline.
11. Treatment with intra-articular joint injection(s) of corticosteroids in the preceding
28 days prior to the Baseline Visit.
12. Treatment with any investigational drug of chemical or biologic nature within a
minimum of 30 days or 5 half lives (whichever is longer) of the drug prior to the
Baseline Visit.
13. Infection(s) requiring treatment with intravenous (IV) anti-infectives within
30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to
the Baseline Visit.
14. Known hypersensitivity to the excipients of adalimumab as stated in the label
(Table 3).
15. History of CNS demyelinating disease or neurologic symptoms suggestive of CNS
demyelinating disease;
16. History of listeriosis, histoplasmosis, chronic or active Hepatitis B infection,
human immunodeficiency virus (HIV) infection, immunodeficiency syndrome,
chronic recurring infections or active TB.
17. History of moderate to severe congestive heart failure (NYHA class III or IV),
recent cerebrovascular accident and any other condition which, in the opinion of
the Investigator, would put the subject at risk by participation in the protocol.
18. Evidence of dysplasia or history of malignancy (including lymphoma and
leukemia) other than a successfully treated non-metastatic cutaneous squamous
cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
19. Positive pregnancy test at Screening or Baseline.
20. Female subjects who are breast-feeding or considering becoming pregnant during
the study.
21. History of clinically significant drug or alcohol abuse in the last 12 months.
22. Clinically significant abnormal screening laboratory results as evaluated by the
Investigator.
23. Positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP)
antibody at Screening.
24. Subject is considered by the Investigator, for any reason, to be an unsuitable
candidate for the study.
25. If entering the study on concomitant oral corticosteroids, subject not on stable dose
of prednisone (≤ 10 mg per/day), or oral corticosteroid equivalents, for at least
14 days prior to the Baseline Visit.
26. Subject with diagnosis and current symptoms of fibromyalgia. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of patients achieving the following
composite response at Week 12:
● ≥ 40% improvement (minimum 20 mm absolute improvement) from Baseline
in Patient Global Assessment of Disease Activity; and
● ≥ 40% improvement (minimum 20 mm absolute improvement) from Baseline
in Patient Global Assessment of Pain; and
● ≥ 40% improvement from Baseline in at least 1 of the following 3 criteria:
o Swollen Joint Count (76 joints) and Tender Joint Count (78 joints)
o Enthesitis Count
o Dactylitis Count |
|
| 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 | Yes |
| 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 | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | No |
| 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.8.3 |
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 | 25 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| The end-of-study is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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