Safety of IFNa Kinoid in Systemic Lupus Erythematosus

• ClinicalTrials.gov Identifier: NCT01058343
• Recruitment Status: Completed
• First Posted: January 28, 2010
• Last Update Posted: March 21, 2019
• Sponsor: Neovacs
• Information provided by (Responsible Party): Neovacs

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Biological: IFN-K	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: March 2010
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: IFN-K 1; IFN kinoid dose 1	Biological: IFN-K; 3 to 4 IM injections over 3 months
Experimental: IFN-K-2; IFN kinoid dose 2	Biological: IFN-K; 3 to 4 IM injections over 3 months
Experimental: IFN-K 3; IFN kinoid dose 3	Biological: IFN-K; 3 to 4 IM injections over 3 months
Experimental: IFN-K 4; IFN kinoid dose 4	Biological: IFN-K; 3 to 4 IM injections over 3 months
Placebo Comparator: Saline; saline at same dose as IFN K	Biological: IFN-K; 3 to 4 IM injections over 3 months

Outcome Measures

Primary Outcome Measures :

1. Frequency and severity of adverse events [ Time Frame: study duration ]

Secondary Outcome Measures :

1. Proportion of patients with anti IFNa antibodies [ Time Frame: Month 4 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Belgium

Cliniques Universitaires St Luc

Brussels, Belgium

Bulgaria

MHAT "Sveti Ivan Rilski"

Sofia, Bulgaria

Croatia

University Hospital Split

Split, Croatia

KBC Zagreb

Zagreb, Croatia

France

Hopital Claude Huriez

Lille, France, 59037

Hopital Lapeyronie

Montpellier, France, 34295

Hopital de la Pitie Salpetriere

Paris, France

Hopital du Kremlin Bicetre

Paris, France

Hopital Haut-Leveque

Pessac, France

Germany

Kerckhoff-Klinik Gmbh

Bad-Nauheim, Germany

Charite

Berlin, Germany

Switzerland

Inselspital

Bern, Switzerland

Geneva University Hospital

Geneva, Switzerland, 1211

Geneva University Hospital

Geneva, Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Sponsors and Collaborators

Neovacs

Investigators

• Principal Investigator: Christian Jorgensen, MD, PhD; Unité Clinique d'Immuno-Rhumatologie Thérapeutique, Hôpital Lapeyronie, Montpellier, France

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Neovacs
• ClinicalTrials.gov Identifier: NCT01058343
• Other Study ID Numbers: IFN-K-001
• First Posted: January 28, 2010
• Last Update Posted: March 21, 2019
• Last Verified: March 2019

Keywords provided by Neovacs:

SLE

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases