Clinical trial NCT01058343: Safety of IFNa Kinoid in Systemic Lupus Erythematosus
Official title: A Phase I-II, Randomized, Double-blind, Placebo-controlled, Dose Escalation Study of Neovacs' IFNα-Kinoid in Adult Subjects With Systemic Lupus Erythematosus.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: SLE
Lead sponsor: Neovacs
Sponsor class: INDUSTRY
First posted: 2010-01-28
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Interferon alpha (IFNa) is involved in the pathogenesis of systemic lupus erythematosus (SLE)and IFNa levels are associated with the severity of the disease. Blocking IFNa could be an attractive therapeutic strategy. Active immunization with IFNa kinoid (IFN-K) induces a polyclonal antibody response.

This study will evaluate the safety of IFN-K in patients with mild to moderate SLE. It will also measure the induction of anti-IFNa antibodies and evaluate the clinical impact on SLE disease.


Eligibility criteria: Inclusion Criteria:

* 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
* 4. Male or female between 18 and 50 years of age
* 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.
* 8. For subjects with reproductive potential (males and females), use of a reliable means of contraception
* 9. Written informed consent obtained from the subject.

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 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 IFNa,
* 8. Received B-cell depleting therapy (e.g. Rituximab) within 12 months
* 9. Received IV antibiotics during the 30 days prior to screening,
* 10. Significant electrocardiogram (ECG) abnormalities ,
* 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
* 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
* 21. Planned use of any investigational or non-registered product

Primary outcomes:
measure: Frequency and severity of adverse events
timeFrame: study duration
Secondary outcomes:
measure: Proportion of patients with anti IFNa antibodies
timeFrame: Month 4
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires St Luc
city: Sofia
country: Bulgaria
facility: MHAT "Sveti Ivan Rilski"
city: Split
country: Croatia
facility: University Hospital Split
city: Zagreb
country: Croatia
facility: KBC Zagreb
city: Lille
country: France
facility: Hopital Claude Huriez
city: Montpellier
country: France
facility: Hopital Lapeyronie
city: Paris
country: France
facility: Hopital de la Pitie Salpetriere
city: Paris
country: France
facility: Hopital du Kremlin Bicetre
city: Pessac
country: France
facility: Hopital Haut-Leveque
city: Bad-Nauheim
country: Germany
facility: Kerckhoff-Klinik Gmbh
city: Berlin
country: Germany
facility: Charite
city: Bern
country: Switzerland
facility: Inselspital
city: Geneva
country: Switzerland
facility: Geneva University Hospital
city: Geneva
country: Switzerland
facility: Geneva University Hospital
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: Unité Clinique d'Immuno-Rhumatologie Thérapeutique, Hôpital Lapeyronie, Montpellier, France
name: Christian Jorgensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ducreux J, Houssiau FA, Vandepapeliere P, Jorgensen C, Lazaro E, Spertini F, Colaone F, Roucairol C, Laborie M, Croughs T, Grouard-Vogel G, Lauwerys BR. Interferon alpha kinoid induces neutralizing anti-interferon alpha antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon alpha kinoid phase I/II study. Rheumatology (Oxford). 2016 Oct;55(10):1901-5. doi: 10.1093/rheumatology/kew262. Epub 2016 Jun 28.
citation: Lauwerys BR, Hachulla E, Spertini F, Lazaro E, Jorgensen C, Mariette X, Haelterman E, Grouard-Vogel G, Fanget B, Dhellin O, Vandepapeliere P, Houssiau FA. Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon alpha-kinoid. Arthritis Rheum. 2013 Feb;65(2):447-56. doi: 10.1002/art.37785.