E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus (SLE) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
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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 |
The primary objective of this trial is to assess the safety and tolerability of three administrations of IFN-K adjuvanted with ISA-51 at four doses (30, 60, 120 or 240 mcg), given on SD0, SD7 and SD28 (+/- a fourth dose on SD84 [Month 3]) in adult subjects with SLE. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives will be: - To evaluate the anti-IFNα antibody response induced by IFN-K. - To evaluate the neutralizing antibody response induced by IFN-K. - To evaluate the cellular immune response in vitro. - To assess the levels of serum auto-antibodies. - To evaluate changes in the expression of IFNa inducible genes in peripheral blood mononuclear cells (PBMCs) in all subjects and in subjects with a positive IFN signature at baseline. - To evaluate the levels of IFNα inducible serum chemokines. - To evaluate the clinical response by assessing: • Disease activity using: o The SLE Disease Activity Index (SLEDAI). o The British Isles Lupus Assessment Group (BILAG) index. o The Physician Global Assessment (PGA) o The SELENA-SLEDAI Flare Index • Quality of life using the SF-36 health care questionnaire.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects must satisfy the following inclusion criteria at study entry: 1. Diagnosis of SLE according to current American College of Rheumatology (ACR) criteria (4 of 11 ACR criteria), 2. SLEDAI #4 and $10, 3. Positive Anti-nuclear Antibodies (ANA) and/or Positive anti-dsDNA antibodies at the time of screening, 4. Male or female between 18 and 50 years of age included at the time of the first planned administration of the study drug, 5. Current immunity to measles, mumps, rubella and varicella, as evidenced by positive IgG titers at the time of screening, 6. For subjects recruited during local influenza season, current vaccination against seasonal influenza at least 7 days prior to randomization, 7. Vaccination against H1N1 influenza at least 7 days prior to randomization. The nasal spray form of the vaccine is not acceptable as it is a live attenuated vaccine, 8. For subjects with reproductive potential (males and females), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, or other barrier method of contraception) throughout their participation in the study, 9. According to the Investigator, able and willing to comply with the requirements of the study protocol (e.g., completion of the diary cards, return for follow-up visits), 10. Written informed consent obtained from the subject. |
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E.4 | Principal exclusion criteria |
The following exclusion criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study: 1. Any serious manifestation of lupus at entry, that, in the opinion of the investigator is likely to require initiation of off-protocol medication changes during the course of the study and in particular no BILAG A score, 2. Any non-SLE manifestation likely to require, in the investigator's judgment, treatment with high-dose corticosteroids or the addition of an immunosuppressive regimen during the course of the trial, 3. Received > 20 mg/day of prednisone equivalent for > 7 days during the 30 days prior to screening, 4. Currently receiving or having received pulse dose corticosteroids or intravenous immunoglobulin (IVIg) within 3 months prior to screening, 5. Received cyclophosphamide within 3 months prior to screening, 6. Received a monoclonal antibody during the 6 months prior to screening, 7. Previously received an investigational treatment directed against IFN!, 8. Received B-cell depleting therapy (e.g. Rituximab) within 12 months prior to screening, 9. Received IV antibiotics during the 30 days prior to screening, 10. Significant electrocardiogram (ECG) abnormalities that are clinically relevant and preclude study entry according to the Investigator’s opinion, 11. Evidence of any clinically significant abnormality on a chest X-ray which, in the opinion of the investigator could represent active infection, latent tuberculosis or treatable manifestation of lupus, 12. Any laboratory abnormality that is clinically relevant and precludes study entry according to the Investigator’s opinion, 13. History of malignancy except completely excised basal cell carcinoma, 14. Congenital immune deficiency, 15. Positive IgM antibody titers in the presence of negative IgG titers to Epstein- Barr virus (EBV) or cytomegalovirus (CMV), 16. Frequent recurrences of oral or genital herpes simplex lesions (# 6 / year), 17. Episode of shingles within one year of screening, 18. Human Immunodeficiency Virus (HIV), hepatitis C virus (HCV) or HBV (HBsAg, anti-HBc ab) positive, 19. Any current signs or symptoms of infection at entry, 20. Administration of any live vaccine within the 3 months prior to study entry (e.g. oral poliomyelitis vaccine, measles-mumps-rubella vaccine, yellow fever vaccine, rotavirus vaccine, varicella vaccine, zoster vaccine, Bacillus Calmette-Guérin vaccine), 21. Planned use of any investigational or non-registered product (drug or vaccine) other than the study product within 30 days preceding the first dose of study product, or during the study period, 22. History of severe allergic or anaphylactic reactions to any component of the kinoid and/or seafood, 23. Pregnancy or lactation, 24. History of chronic alcohol consumption and/or drug abuse within 6 months of screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints:
• Occurrence, intensity and relationship to IFN-K immunization of any solicited local and general signs and symptoms during a 7-day follow up period (i.e. Day of study drug administration and 6 subsequent days) after each IFN-K dose. • Occurrence, intensity and relationship to IFN-K immunization of unsolicited local and general signs and symptoms occurring throughout the study period. • Occurrence and relationship to IFN-K immunization of all serious adverse events (SAE) occurring throughout the study period. • Occurrence, intensity and relationship to IFN-K immunization of any abnormality in physical examination, vital signs, 12-lead ECG, clinical laboratory evaluations, and adverse events (AEs). |
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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 | 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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 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
| 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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |