E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Axial Spondyloarthritis (SpA) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10041672 |
E.1.2 | Term | Spondylitis ankylosing |
E.1.2 | System Organ Class | 100000004859 |
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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 evaluate the effect of golimumab50 mg compared to placebo in the treatment of active axial SpA, as measured by proportion of subjects achieving Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 16 and to demonstrate the safety and tolerability of golimumab 50 mg through Week 16 in the active axial SpA population. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the treatment effect of golimumab 50 mg compared to placebo as measured by the proportion of subjects achieving ASAS 40 response at Week 16.
To evaluate the treatment effect of golimumab 50 mg compared to placebo, as measured by the proportion of subjects who achieve Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response at Week 16.
To evaluate the treatment effect of golimumab 50 mg compared to placebo, as measured by the proportion of subjects who achieve ASAS partial remission at Week 16.
To evaluate the treatment effect of golimumab 50 mg compared to placebo by the change in the Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Sacroiliac (SI) joints scoring from Baseline to Week 16.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Each subject must be ≥18 to ≤45 years of age.
2. Each subject must have a physician’s diagnosis of active axial SpA with disease duration ≤5 years, and chronic back pain of ≥3 month duration.
3. Each subject must meet either criterion “a” or “b” as adopted from ASAS classification criteria:
a. Active inflammation on MRI highly suggestive of sacroiliitis associated with spondyloarthropathy (as evidenced by the central reader) and 1 or more of the following spondyloarthritis characteristics OR
b. HLA-B27+ gene and 2 or more of the following spondylarthritis characteristics (not including HLA-B27):
◦ Inflammatory back pain, defined as having at least 4 out of the 5 following parameters:
age at onset < 40 years;
insidious onset;
improvement with exercise;
no improvement with rest;
pain at night (with improvement upon getting up);
◦ Arthritis diagnosed by a physician;
◦ Enthesitis diagnosed by a physician;
◦ Dactylitis diagnosed by a physician;
◦ Psoriasis diagnosed by a physician;
◦ History of inflammatory bowel disease (IBD) diagnosed by a physician;
◦ History of uveitis confirmed by an ophthalmologist;
◦ Good response to NSAIDs
◦ Family history for SpA;
◦ Elevated CRP (> upper limit of normal based on central lab values);
◦ HLA-B27+ gene;
4. Each subject must show high disease activity at Screening and Baseline of both a total back pain evaluation of ≥40 mm on a VAS of 0-100 mm and a BASDAI score of ≥ 40 mm.
5. Each subject must have either an inadequate response (as assessed by the investigator) to 30 days of continuous therapy with maximal recommended daily doses of at least one non-steroidal anti-inflammatory drug (NSAID) or must be unable to receive a maximal dose of NSAID therapy for a full 30 days because of intolerance, toxicity, or contraindications to NSAIDs.
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E.4 | Principal exclusion criteria |
1. The subject has bilateral sacroiliitis Grade 2 or unilateral sacroiliitis Grade 3 or Grade 4 on conventional X-rays (ie, excluding modified New York criteria) based on central reading at Screening.
2. The subject has ever received TNF-α targeted therapy or any biological agents, including but not limited to infliximab, etanercept, adalimumab, alefacept or efalizumab, rituximab, or natalizumab.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for the trial is the proportion of subjects meeting the ASAS 20 response at Week 16. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The Key Secondary Efficacy Endpoints are:
• Proportion of subjects meeting the ASAS 40 response at Week 16;
• Proportion of subjects achieving BASDAI 50 at Week 16;
• Proportion of subjects in ASAS partial remission at Week 16;
• Change in SPARCC MRI SI joints scoring from Baseline to Week 16.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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
| 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Canada |
Czech Republic |
Denmark |
Germany |
Greece |
Ireland |
Italy |
Norway |
Russian Federation |
Spain |
Turkey |
United Kingdom |
United States |
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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
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The overall trial ends when the last remaining subject has ended participation in the trial, by completing the trial, being discontinued from the trial, or being lost to follow-up. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 15 |