Systemic Lupus Erythematosus (SLE) MedDRA version: 14.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: IFN-a2b Kinoid
Product Code: IFN-K
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Not assigned yet
Current Sponsor code: IFN-K DS
Other descriptive name: IFN-a 2b Kino
Sponsors
Neovacs SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 randomiza7. Vaccination against H1N1 influenza at least 7 days prior to randomization, if judged indicated by the Investigator. 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, (i.e. until study Day 168 (Month 6 study visit), unless additional extended follow up visits are needed in the presence of persisting anti-IFNa antibodies. In this case, contraception must be continued until anti-IFNa antibody levels are back to baseline and further follow visits are no longer required, 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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 highdose corticosteroids or the addition of an immunosuppressive regimen during the course of the trial, 3. Received > 20 mg/day of prednisone, or 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 alpha , 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, in particular subjects with already impaired functions of central organs at screening (e.g. AST > 2.5 x upper limit of the norm (ULN), ALT > 2,5 x ULN, creatinine > 1,5 x ULN, serum potassium above or below the normal range, hemoglobin < 8g/dL, WBC < 1,800/mm3, neutrophils < 1,500/mm3, platelet count < 50,000/mm3, lupus with central manifestation) should be excluded from the study. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: The secondary objectives will be: - To evaluate the anti-IFNa 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 IFNa 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. ;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). | — |
Countries
Belgium, Bulgaria, France, Germany
Outcome results
None listed