Safety of IFNa Kinoid in Systemic Lupus Erythematosus

NCT ID: NCT01058343

Last Updated: 2019-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2016-06-30

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

IFN-K 1

IFN kinoid dose 1

Group Type: EXPERIMENTAL

IFN-K

Intervention Type: BIOLOGICAL

3 to 4 IM injections over 3 months

IFN-K-2

IFN kinoid dose 2

Group Type: EXPERIMENTAL

IFN-K

Intervention Type: BIOLOGICAL

3 to 4 IM injections over 3 months

IFN-K 3

IFN kinoid dose 3

Group Type: EXPERIMENTAL

IFN-K

Intervention Type: BIOLOGICAL

3 to 4 IM injections over 3 months

IFN-K 4

IFN kinoid dose 4

Group Type: EXPERIMENTAL

IFN-K

Intervention Type: BIOLOGICAL

3 to 4 IM injections over 3 months

Saline

saline at same dose as IFN K

Group Type: PLACEBO_COMPARATOR

IFN-K

Intervention Type: BIOLOGICAL

3 to 4 IM injections over 3 months

Interventions

IFN-K

3 to 4 IM injections over 3 months

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neovacs

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Jorgensen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Unité Clinique d'Immuno-Rhumatologie Thérapeutique, Hôpital Lapeyronie, Montpellier, France

Locations

Cliniques Universitaires St Luc

Brussels, , Belgium

MHAT "Sveti Ivan Rilski"

Sofia, , Bulgaria

University Hospital Split

Split, , Croatia

KBC Zagreb

Zagreb, , Croatia

Hopital Claude Huriez

Lille, , France

Hopital Lapeyronie

Montpellier, , France

Hopital de la Pitie Salpetriere

Paris, , France

Hopital du Kremlin Bicetre

Paris, , France

Hopital Haut-Leveque

Pessac, , France

Kerckhoff-Klinik Gmbh

Bad Nauheim, , Germany

Charite

Berlin, , Germany

Inselspital

Bern, , Switzerland

Geneva University Hospital

Geneva, , Switzerland

Geneva University Hospital

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Countries

Belgium; Bulgaria; Croatia; France; Germany; Switzerland

References

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.

Reference Type: DERIVED

PMID: 27354683 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23203821 (View on PubMed)

Other Identifiers

IFN-K-001

Identifier Type: -

Identifier Source: org_study_id