E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with have a diagnosis of primary SS according to the updated American European Consensus Group Criteria (8). In addition, patients must be always positive for anti-SSA or anti-SSB antibodies (of note, the quasi totality of patients positive for anti-SSB are also positive for anti-SSA) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021428 |
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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 proof of concept of efficacy of belimumab in subjects with SS To evaluate the safety and tolerability of belimumab in subjects with SS |
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E.2.2 | Secondary objectives of the trial |
1. ≥ 30% reduction of patient’s dryness VAS 2. ≥ 30% reduction of patient’s fatigue VAS 3. ≥ 30% reduction of patient’s musculoskeletal pain VAS 4. ≥ 30% reduction of physician’s systemic activity VAS 5. ≥ 25% reduction of serum levels of any of the following B cell activation biomarkers (IgG, free light chain of immunogobulins, beta2-microglobulin, monoclonal component, cryoglobulinemia) or ≥ 25% C4 increase 6. ≥ 30% reduction of Physician’s Global Assessment (PGA)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Are at least 18 years of age - Have a diagnosis of primary SS. In addition, patients must be always positive for anti-SSA or anti-SSB antibodies. Have the presence, at screening, of a)Systemic involvement or persistent (≥ 2 months) parotid, submandibular or lacrymal gland swelling of more than 2 cm OR b) Objective sicca (positive oral and/or ocular tests reported in the American European Consensus Group Criteria) with at least one among the following biological features of serum B lymphocyte activation : - increased IgG levels (>15g/L) - increased free light chain levels of immunoglobulins (according to central laboratory ranges) - increased serum beta2-microglobulin levels - decreased C4 levels (C4 levels inferior to central laboratory ranges) - monoclonal gammapathy - cryoglobulinemia
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E.4 | Principal exclusion criteria |
Have received treatment with any BLyS-targeted - Have received any of the following within 364 days of Day 0: B-cell targeted therapy Abatacept A biologic investigational agent other than B cell targeted therapy - Have required 3 or more courses of systemic corticosteroids for concomitant conditions within 364 days of Day 0. Have received intravenous (IV) or oral cyclophosphamide within 180 days of Day 0 - Have received any of the following within 90 days of Day 0: Anti-TNF therapy, Anakira, Intravenous immunoglobulin (IVIG), prednisone > 100 mg/day, Plasmapheresis. Have received any sperimental new drug. Have received any of the following within 30 days of Day 0: A change in dose of a corticosteroid, other immunosuppressive/immunomodulatory agent, anti-malarial, NSAID) Have a history of a major organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. 10. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SS. Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix. 13. Have required management of acute or chronic infections Hospitalization for treatment of infection within 60 days of Day 0. Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 0. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0. Positive Pregnancy Test Not informed consens |
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E.5 End points |
E.5.1 | Primary end point(s) |
• A response is defined as: • Fulfillment of any 2 of the 5 following response criteria: o ≥ 30% reduction of patient’s dryness VAS o ≥ 30% reduction of patient’s fatigue VAS o ≥ 30% reduction of patient’s musculoskeletal pain VAS o ≥ 30% reduction of physician’s systemic activity VAS o ≥ 25% reduction of serum levels of any of the following B cell activation biomarkers (free light chains of immunogobulins, beta2-microglobulin, monoclonal component, cryoglobulinemia, IgG) or ≥ 25% C4 increase The choice of improvement of 2 of the 5 criteria is justified by the fact that some patients could be improved only on systemic signs, and thus could be improved on the 2 last items (physician VAS and B-cell biomarkers). Conversely, a patient with no systemic sign could be included in case of increase of B-cell biomarkers. If his B-cell markers do not change, he could benefit from the drug if 2 out of his 3 VAS (dryness, fatigue, pain) improve. |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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Decesso del paziente - Assunzione di farmaci non permessi dal protocollo - Ritiro precoce per peggioramento clinico - Peggioramento della malattia alla settimana 28. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 13 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |