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198 IFN-kinoid in systemic lupus erythematosus (SLE): results from a phase 2b, randomized, placebo-controlled study
  1. Frédéric Houssiau1,
  2. Aikaterini Thanou2,
  3. Minodora Mazur3,
  4. Edgar Ramiterre4,
  5. Danny Alexis Gomez Mora5,
  6. Maria Misterska-skora6,
  7. Risto Perich Campos7,
  8. Svetlana Anatolyevna Smakotina8,
  9. Sergio Cerpa Cruz9,
  10. Bassem Louzir10,
  11. Therese Camille11 and
  12. Michael Tee12
  1. 1Service de Rhumatologie, Cliniques universitaires Saint-Luc, Brussels and Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Université catholique de Louvain
  2. 2Research Affiliate Arthritis and Clinical Immunology Research Program Oklahoma Medical Research Foundation
  3. 3University Professor at State Medical and Pharmaceutical University
  4. 4Section of Rheumatology, Department of Internal Medicine, Southern Philippines Medical Center JP Laurel Ave, Davao City Philippines
  5. 5Rheumatologist from UNIVERSIDAD NACIONAL DE COLOMBIA Healthy Medical Center Kra 4 # 7–39 Zipaquira
  6. 6Medical Center Oporów Solskiego 4a/1 52–416 Wrocaw
  7. 7Rheumatology Department, Hospital Nacional Guillermo Almenara Irigoyen. EsSalud. Lima- Perú. Universidad Nacional Mayor de San Marcos
  8. 8Doctor of medical sciences, professor of Kemerovo State Medical University
  9. 9Attending Physician and Associated Clinical Professor Medicine/Rheumatology Department Hospital Civil de Guadalajara
  10. 10Head of Department of Internal Medicine Military hospital of Tunis 1008 Tunis
  11. 11Neovacs
  12. 12Vice Chancellor Medical Center Manila, Rheumatology Department UP Manila College of Medicine and ManilaMed

Abstract

Background The immunotherapeutic vaccine Interferon--kinoid (IFN-K) consists of a heterocomplex of inactivated recombinant human IFN-2b coupled to a T-helper carrier protein, Keyhole Limpet Haemocyanin. A phase I/IIa was published. Here, we report the results of a 36 week (w) phase 2b, randomized, double-blind, placebo-controlled (PBO), multi-center study assessing the efficacy and safety of IFN-K in patients with active SLE on standard of care therapy.

Methods SLE patients (4 ACR criteria) with moderate to severe disease activity (SLEDAI 2K 6 and 1 BILAG A and/or 2 BILAG B scores); positive IFN gene signature; and ANA and/or anti-dsDNA, were randomized (1:1) to 5 IM injections of IFN-K or PBO at days 0, 7, 28, and months 3 and 6. Co-primary objectives at w36 were neutralization of IFN gene signature and BICLA response modified by mandatory corticosteroid (CS) tapering (5 mg/d prednisolone equivalent) by w24 with no increase to w36. Secondary objectives at w36 were SRI(4) and SRI(4) with CS tapering (5 mg or 7.5 mg/d prednisolone equivalent) by w36, Lupus Low Disease Activity State (LLDAS), safety and immunogenicity.

Results Among 185 patients randomized, 91 and 93 were respectively treated with IFN-K and PBO, and 85 (92.4%) and 84 (90.3%) completed the study. Seventy-two of 79 (91.1%) IFN-K treated patients (Per Protocol Set) developed anti-IFN neutralizing antibodies (Abs). Primary and secondary outcome measures at w36 are detailed in the Table:

IFN-K was well tolerated, with similar rates of treatment-emergent adverse events (TEAEs 82.4% vs 76.3%) and TEAEs leading to study drug discontinuation (4.4% vs. 4.3%) in the IFN-K and PBO groups, respectively. Serious adverse events (SAEs) were more common on PBO vs IFN-K (12.9% vs 6.6%). Cancer (n=4) and lupus nephritis (n=2) were reported in the PBO group and there was one severe infection in the IFN-K group. One death occurred in each group.

Abstract 198 Table 1

Conclusions IFN-K induced neutralizing anti-IFN Abs in 91.1% of treated patients and significantly reduced IFN gene signature. Modified BICLA at w36 did not differ between IFN-K and PBO. Trends on SRI (4) with steroid tapering at w36 favored IFN-K, and became significant when patients exhibiting neutralizing Abs were included in the exploratory analysis. Furthermore achieving a Lupus Low Disease Activity State discriminated the two groups at w36, in favor of IFN-K. A significant CS sparing effect of IFN-K was observed from w28 onwards. The safety profile of IFN-K was acceptable. Results merit further evaluation in phase 3 studies.

Funding Source(s): The study was funded by Neovacs.

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