| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early stage peripheral Spondyloarthritis (SpA) |
| Vroegtijdige Perifere sponyloarthropathie |
|
| E.1.1.1 | Medical condition in easily understood language |
| Early stage Peripheral Spondyloarthritis |
| Perifere spondyloarthropathie met vroegtijdige aantasting |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10056449 |
| E.1.2 | Term | Spondyloarthrosis |
| E.1.2 | System Organ Class | 100000004859 |
|
| 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 |
To explore the potential of an induction therapy with the TNF-blocking agent golimumab (Simponi® in a very early disease stage (less than 3 months of symptom duration) of patients with predominant peripheral Spondyloarthritis (SpA), classified according to the new ASAS-criteria.
In the open-label ‘CRESPA-extension’ part of the study, we want to investigate the long-term safety and efficacy of golimumab administered every 4 weeks at a dose of 50 mg subcutaneously (SC) for a total period of 116 weeks (104 weeks golimumab monotherapy + 12 weeks combination therapy with methotrexate 10-15 mg weekly). |
|
| E.2.2 | Secondary objectives of the trial |
Exploration for:
- The improvement in the tender and swollen joint count.
- The improvement in dactylitis with obtaining a circumference measurement and clinical picture.
- The improvement in enthesitis, using the different scoring systems with inclusion of all relevant entheses.
- The improvement in global measurements of disease activity: patient global assessment of disease activity, patient pain assessment (peripheral and axial pain), physician global assessment of disease activity, ...)
- Of the utility of conventional ankylosing spondylitis measurements such as BASDAI, BASFI, BASMI
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Subject is ≥ 18 years of age
- Subjects must meet the new ASAS classification criteria for peripheral spondyloarthritis
- Subjects must have had onset of peripheral SpA symptoms ≤ 3 months prior to the screening visit
- Subjects must have active disease at screening and baseline, defined by Patient Global Assessment of Disease Activity VAS ≥ 40mm and Patient Global Assessment of Pain VAS ≥ 40mm at screening and baseline visits.
- 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.
- Subject has a negative PPD test (or equivalent) and Chest radiography (PA and lateral view) at screening. If the subject has a positive PPD test (or equivalent), has had a past ulcerative reaction following PPD placement and/or a Chest radiography consistent with prior TB exposure, the subject must initiate, or have documented completions of a course of anti-TB therapy.
- Patients must undergo screening for HBV (this includes testing for HBsAg (surface antigen), anti-HBs (surface antibody) and anti-HBc total (core antibody total).
- Women of childbearing potential or men capable of fathering children must be using adequate birth control measures during the study and for 6 months after receiving the last administration of study agent. Female patients of childbearing potential must test negative for pregnancy.
- 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 6 months after last dose of study drug.
- Female subjects must agree to not donate eggs (ova, oocytes) during the study and for 6 months after last dose of study agent. Male subjects must agree to not donate sperm while in the study and for 6 months after last dose of study agent
- 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.
- Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
- Subjects must be able and willing to self-administer sc injections or have a qualified person available to administer sc injections.
CRESPA-Extension’
Subjects will be allowed to participate in the ‘CRESPA-Extension’ part of the study if they are considered good candidates for chronic anti-TNF treatment and fulfill one of the following 2 scenarios:
- Patients participating in ‘CRESPA’ that experienced “sustained clinical remission of arthritis/enthesitis/dactylitis on 2 consecutive major study visits, and in whom withdrawal of golimumab treatment provoked a flare of peripheral SpA during the follow-up.
- Patients participating in ‘CRESPA’ that experienced a major improvement at the week 48 ‘end-of-study’ visit, without however reaching clinical remission. Major improvement is defined as “Peripheral SpA Response Criteria at 40%” (PSpARC 40):
- ≥40% improvement (minimum 20 mm absolute improvement) from baseline in Patient Global Assessment of Disease Activity on a 100 mm Visual Analogue Scale (VAS) and
- ≥40% improvement (minimum 20 mm absolute improvement) from baseline in Patient Global Assessment of Pain on a 100 mm Visual Analogue Scale (VAS) and
- ≥40% improvement from baseline in at least 1 of the following 3 criteria:
- Swollen 76-Joint Count (SJC) and Tender 78-Joint Count (TJC)
- Enthesitis Count
- Dactylitis Count
|
|
| E.4 | Principal exclusion criteria |
- 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).
- Prior exposure to any biologic therapy with a potential therapeutic impact on SpA, including anti-TNF therapy.
- Treatment with any investigational drug of chemical or biological nature within a minimum of 30 days or 5 half lives (whichever is longer) of the drug prior to the Baseline Visit.
- 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.
- Have a known hypersensitivity to human immunoglobulin proteins or other components of golimumab.
- History of CNS demyelinating disease or neurologic symptoms suggestive of CNS demyelinating disease.
- History of listeriosis, histoplasmosis, chronic of active Hepatitis B infection, Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active TB.
- Have a history of, or concurrent, CHF, including medically controlled, asymptomatic CHF.
- 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.
- Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months prior to the first administration of study agent, during the trial, or within 6 months after the last administration of study agent.
- Positive pregnancy test at screening or baseline.
- Female subjects who are breast-feeding or considering becoming pregnant during the study.
- History of clinically significant drug or alcohol abuse in the last 12 months.
- Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
- Positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibody at screening if the titers are crossing 3 times the upper limit of the normal
- Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
- Subject with diagnosis and current symptoms of fibromyalgia. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
the induction of clinical remission (complete resolution of synovitis/dactylitis/enthesitis which was present at baseline) and prevention of newly developing peripheral and/or axial spondylarthritis signs).
The primary analysis will be a comparison at 24 weeks of the percentage of patients with a PSpARC 40 response in the group treated with the TNF-blocking agent versus placebo (for patients who were treated via the open-label Golimumab escape arm, an approach based upon last observation carried forward (LOCF) and non-responder imputation (NRI) will be used). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
I. In this study we will also evaluate the safety of TNF-α blockade in patients with early peripheral spondyloarthritis.
II. Comparison between the group treated with the anti-TNF blocking agent versus placebo at week 12 (and if applicable at week 24) for:
The percentage of patients achieving Peripheral Spondyloarthritis Response Criteria at different levels of response (e.g. PSpARC 40).
The percentage of patients for whom early escape was necessary.
The improvement in the tender and swollen joint count.
The improvement in dactylitis count and semiquantitative score of severity (mild, moderate, severe).with obtaining a circumference measurement and clinical picture.
The improvement in enthesitis count, using the different scoring systems with inclusion of all relevant entheses.
The improvement in global measurements of disease activity: patient global assessment of disease activity, patient pain assessment (peripheral and axial pain), physician global assessment of disease activity, ...).
The exploration of the utility of conventional ankylosing spondylitis measurements such as BASDAI, BASFI, BASMI.
III. Longitudinal comparison versus baseline of efficacy parameters described below over the first 24 weeks. Potentially 3 groups will be compared: the group treated with placebo until week 24, the group treated with placebo until week 12 followed by the anti-TNF blocking agent, and the group treated with the anti-TNF blocking agent from baseline.
The percentage of patient in clinical remission (absence of arthritis, enthesitis and dactylitis).
The improvement in the tender and swollen joint count.
The improvement in dactylitis count and semiquantitative score of severity (mild, moderate, severe).
The improvement in enthesitis count, using the different scoring systems with inclusion of all relevant entheses.
The improvement in global measurements of disease activity: patient global assessment of disease activity, patient pain assessment (peripheral and axial pain), physician global assessment of disease activity, ...).
The exploration of the utility of conventional ankylosing spondylitis measurements such as BASDAI, BASFI, BASMI.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- at 3 months (week 12) in comparison with baseline
- at 6 months (week 24) in comparison with baseline |
|
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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 | 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 | 0 |
| 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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