Systemic Lupus Erythematosus MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: IFN-Kinoid
Product Code: IFN-K
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Not yet assigned
Current Sponsor code: IFN-K DS
Other descriptive name: IFN-Kinoid Drug Su
Sponsors
Neovacs S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient meeting all of the following inclusion criteria at screening will be eligible for participation in the study: 1. Has had a diagnosis of SLE according to current ACR criteria (4 of 11 ACR criteria) 2. Has SLEDAI-2K = 6 3. Has at least 1 BILAG A and/or at least 2 BILAG B 4. Has a positive IFN gene signature by RT-qPCR as assessed on a limited number of genes 5. Has anti-nuclear antibodies (ANA) = 1:160 and/or anti-dsDNA antibodies = 7.0 IU/mL 6. Be a male or female, aged between 18 and 65 years, inclusive, at the time of the screening visit 7. Agrees to receive influenza vaccination during each influenza season of the study period 8. Currently receiving at least one of the following treatment: • Corticosteroids (CS) at a dose of = 20 mg of prednisone equivalent/day • Antimalarial drugs (hydroxychloroquine [HCQ] or chloroquine [CQ]); the patient must have been treated since at least 8 weeks and on stable dose for at least 4 weeks prior to first planned administration of the study product • Methotrexate (MTX); the patient must have been treated and be on stable dose (= 20 mg/week) for at least 12 weeks prior to the first planned administration of the study product • Azathioprine (AZA); the patient must have been treated and be on stable dose (= 2.5 mg/kg/day) for at least 12 weeks prior to the first planned administration of the study product • Mycophenolate mofetil (MMF), the patient must have been treated and be on stable dose (= 2 g/day) for at least 12 weeks prior to the first planned administration of the study product 9. Study patient and his/her partner has to use effective method of contraception for the duration of the study including the Extended Follow-up Period. Note: If of child-bearing potential, effective contraception methods include: - Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks prior to the first planned administration of the study product. In case of oophorectomy alone, the reproductive status of the woman must be confirmed by follow up hormone level assessment. - Male sterilization (at least 6 months prior to Screening). - Combination of the following: • Oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or • Placement of an intrauterine device (IUD) or intrauterine system (IUS) • And barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, she is considered not of child bearing potential only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. 10. Is able and willing to comply with the requirements of the study protocol (e.g., completion of the diary cards, return for follow-up visits), in the opinion of the Investigator 11. Has provided written informed consent Are the trial subjects under 18? no Number of subjects for
Exclusion criteria
Exclusion criteria: A patient meeting any of the following exclusion criteria at study entry will not be eligible for the study: 1. Has active, severe lupus nephritis as defined either by the immediate need for cyclophosphamide treatment or by renal BILAG A 2. Has active, severe, neuropsychiatric SLE, defined as neuropsychiatric BILAG A 3. During the 4 months prior to the first planned administration of the study product, has been treated with corticosteroids (CS) at a dose of >20 mg of prednisone equivalent/day for > 7 consecutive days 4. Is currently receiving or has received pulse dose CS (= 250 mg prednisone equivalent/day) within 3 months prior to the first planned administration of the study product 5. Has received potent immunosuppressive drugs such as cyclophosphamide, cyclosporine A, oral tacrolimus within 3 months prior to the first planned administration of the study product 6. Has received abatacept, sifalimumab, rontalizumab, anifrolumab, belimumab, TNF antagonists or another registered or investigational biological therapy within 6 months prior to the first planned administration of the study product 7. Has received anti-B-cell therapy (e.g., rituximab, epratuzumab) within 12 months prior to the first planned administration of the study product 8. Has significant electrocardiogram (ECG) abnormalities that are clinically relevant and preclude study eligibility in the Investigator’s opinion 9. Has inflammatory joint or skin disease other than SLE that may interfere with study assessments 10. Has any laboratory abnormality that is clinically relevant and precludes study entry in the Investigator’s opinion 11. Has a history of malignant cancer, except the following treated cancers: cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma. For US patients only: Has a history of malignant cancer, except the following treated cancer: basal cell carcinoma. Note: only patients with negative screening tests for malignancy according to The American Cancer Society guidelines (see Appendix 12), documented within the 12 months prior screening visit will be enrolled. 12. Has frequent recurrences of oral or genital herpes simplex lesions (= 6 occurrences during the 12 months prior to first study product administration) 13. Has had an episode of shingles during the 12 months prior to the first planned administration of the study product 14. Has no IgG against herpes simplex virus (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV) or Epstein-Barr virus (EBV) 15. Is positive for HTLV 1-2 antibodies, HIV antibodies, Hepatitis C (HCV) antibodies, or Hepatitis B surface antigen (HBsAg) 16. Is at high risk of significant infection and/or has any current signs or symptoms of infection at entry or has received intravenous antibiotics within 2 months prior to the first planned administration of the study product 17. Has received any live vaccine within 3 months prior to the first planned administration of the study product (e.g. nasal flu vaccine, oral poliomyelitis vaccine, measles-mumps-rubella vaccine, yellow fever vaccine, Japanese encephalitis vaccine, dengue vaccine, rotavirus vaccine, varicella vaccine, zoster vaccine, Bacillus Calmette-Guérin [BCG] vaccine, oral typhoid vaccine) 18. Has used any investigational or non-registered product within 30 days or 5 half-lives, whichever is longer, or any investigational or non-registered vaccine within 30 days prior to the first planned admini
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: The primary objective of the main study (at week 36) is to evaluate the neutralization of the IFN gene signature following treatment with IFN-K, as measured by the change from baseline of the expression of IFN-induced genes and to evaluate the efficacy of treatment with IFN-K using the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response criteria. The study will be considered as positive if a statistically significant better effect of IFN-K compared to placebo is observed on the neutralization of the IFN gene signature and if at least a trend favoring IFN-K is observed on the BICLA response.;Secondary Objective: Secondary Objectives The secondary objectives of this study are: •To evaluate the efficacy of treatment with IFN-K using: - The SLE Responder Index [(SRI)-4 and above] - The SLE Disease Activity Index-2000 (SLEDAI-2K) - The BILAG-2004 index - The Safety of Estrogen in Lupus Erythematosus National Assessment-SLEDAI (SELENA-SLEDAI) Flare index - The Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index for Systemic Lupus Erythematosus (SLICC/ACR DI) - The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in patients with cutaneous lesions at baseline -The Lupus Low Disease Activity State (LLDAS) •To evaluate the immune response induced by IFN-K - Anti-IFNa antibody response - Anti-Keyhole Limpet Hemocyanin (KLH) antibody response - Anti-IFNa antibody neutralizing capacities •To assess the safety of IFN-K emulsified with ISA 51 VG ;Primary end point(s): Two co-primary endpoints will be evaluated in the trial: • Change from baseline in the expression of IFN-induced genes at Week 36. • Response to treatment with IFN-K as measured by the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response criteria at Week 36: - All BILAG A scores at baseline improve to B/C/D and all BILAG B scor | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical secondary endpoints: • Response to treatment with IFN-K, as measured by the SLE Responder Index (SRI)-4 response criteria at Week 36: - Reduction = 4 points in SELENA-SLEDAI and - No new BILAG A and - No more than 1 new BILAG B and - No deterioration in PGA (< 10% worsening) on VAS 100 mm compared with baseline • Response to treatment with IFN-K, as measured by SLEDAI response, defined as a reduction of the SLEDAI-2K score of at least 4 points at Week 36 compared to baseline • Response to treatment with IFN-K, as measured by BILAG grade changes by body system • Response to treatment with IFN-K, as measured by incidence of SLE flare (SELENA SLEDAI flare index, BILAG flares) • Response to treatment with IFN-K, as measured by SLICC/ACR-DI • Response to treatment with IFN-K, as measured by Cutaneous LE Disease Area and Severity Index (CLASI) • Attainment of Lupus Low Disease Activity State (LLDAS) as assessed at each extended follow up visit Immunogenicity secondary endpoints: At timepoints specified on the flow chart, Geometric Mean Titers (GMT) and seroconversion rates for: • Anti-IFNa binding antibody titers • Anti-IFNa neutralizing antibody titers • Anti-KLH binding antibody titers Safety endpoints: • Occurrence, intensity and relationship of any solicited local and systemic AEs during a 7-day follow-up period (i.e. day of study product administration and 6 subsequent days) after each IFN-K or placebo dose • Occurrence, intensity and relationship of unsolicited local and systemic AEs occurring throughout the study period • Occurrence and relationship of all SAEs occurring throughout the study period • Occurrence and intensity of solicited injection site reactions 1 hour post study product administration • Occurrence and intensity of solicited systemic reactions 1 hour post study product administration • Hematological and biochemical levels within or outside the normal ranges and percent change from baseline | — |
Countries
Argentina, Belgium, Bulgaria, Chile, Colombia, Croatia, France, Georgia, Germany, Italy, Korea, Republic of, Mexico, Moldova, Republic of, Peru, Philippines, Poland, Russian Federation, Serbia, Spain, Switzerland, Taiwan, Thailand, Tunisia, Ukraine, United States
Contacts
Public ContactThérèse CROUGHS
Neovacs S.A.
Outcome results
None listed