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Trial record 1 of 1 for:    IFN-K 002
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Phase IIb Study of IFN-K in Systemic Lupus Erythematosus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02665364
Recruitment Status : Terminated (Reorganization proceedings of the sponsor)
First Posted : January 27, 2016
Results First Posted : March 26, 2020
Last Update Posted : April 9, 2020
Sponsor:
Information provided by (Responsible Party):
Neovacs

Tracking Information
First Submitted Date  ICMJE November 17, 2015
First Posted Date  ICMJE January 27, 2016
Results First Submitted Date  ICMJE February 6, 2020
Results First Posted Date  ICMJE March 26, 2020
Last Update Posted Date April 9, 2020
Actual Study Start Date  ICMJE September 23, 2015
Actual Primary Completion Date March 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2020)
  • Percent Change From Baseline in IFN Gene Signature at W36 [ Time Frame: Baseline and Last Available Value (LVA) between week 24 and week 36 ]
    The biological endpoint aimed at evaluating the neutralization of the IFN gene signature following treatment with IFN-K compared to placebo, as measured by the % change from baseline of the expression of IFN-induced genes.
  • Number of Participants Who Achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) With Superimposed CS Tapering at Week 36 [ Time Frame: At Week 36 ]
    British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responder was defined as a subject who had the following criteria at week 36:
    • All BILAG A scores at baseline improve to B/C/D and all BILAG B scores improve to C/D at W36, and
    • No BILAG worsening in other body systems: no new BILAG A or ≥ 2 new BILAG B scores at W36, and
    • No worsening in SLEDAI-2K total score at W36 compared with baseline, and
    • No deterioration in Physician Global Assessment (PGA) (< 10% worsening) on Visual Analog Scale (VAS) 100 mm at W36 compared with baseline, and
    • No addition or increased dose level of anti-malarial drugs or immunosuppressive drugs or CS* between W24 and W36 (*≤5 mg prednisolone or equivalent /day at W24 and no increase until W36).
Original Primary Outcome Measures  ICMJE
 (submitted: January 22, 2016)
  • Change from baseline in the expression of IFN-induced genes at Week 36 [ Time Frame: 9 months ]
  • 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 [ Time Frame: 9 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2020)
  • Number of Participants Who Achieved a Systematic Lupus Erythematosus (SLE) Responder Index (SRI)-4 at Week 36 [ Time Frame: W36 (9 months) ]
    SLE Responder Index (SRI); SRI-4 responder was defined as a subject who had the following criteria at week 36:
    • reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and
    • no new BILAG A at week 36, and
    • no more than 1 new BILAG B at week 36, and
    • no deterioration in PGA (<10% worsening) on 100-mm VAS compared with baseline
  • Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) at Week 36 [ Time Frame: At Week 36 ]
    Lupus low disease activity state (LLDAS) was conceptually defined as 'a state which, if sustained, is associated with a low likelihood of adverse outcome, considering disease activity and medication safety'. Subsequently defined using consensus methodology, LLDAS is attained if all the following items are met:
    • SLEDAI-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity
    • No new features of lupus disease activity compared with the previous assessment
    • SELENA-SLEDAI physician global assessment (PGA, scale 0-3) ≤1
    • Current prednisolone (or equivalent) dose ≤7.5 mg daily
    • Well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs
  • BILAG Global Score Change From Baseline to Last Available Value (LVA) Between Week 24 and Week 36 [ Time Frame: Last Available Value (LVA) between week 24 and week 36 ]
    British Isles Lupus Assessment Group (BILAG)-2004 index, it categorizes disease activity into 5 different levels from A to E, with Grade A representing very active disease and Grade E indicating no current or previous disease activity. Scoring was based on a total of 101 items, grouped into 9 organ/systems and the summation of the numerical values for the nine-system scores was given by the following formula: Numerical global score = A*12 + B*8 + C*1, where A, B and C represent the number of Grades A, B and C respectively at each assessment. Grades D and E are considered as 0 (Chee-Seng Yee et al, 2010). The minimum score is 0 with no predefined maximum. The higher scores mean a worse outcome. The BILAG global score change from baseline to Last Available Value (LVA) week 24 and week 36 were presented analyzed.
  • SELENA-SLEDAI - Change From Baseline to Week 36 [ Time Frame: Baseline and Week 36 ]
    Safety of Estrogens in Systemic Lupus Erythematosus National Assessment (SELENA)-SLEDAI, is a slightly modified version of the SLEDAI. This is a weighted index in which signs and symptoms, laboratory tests, and Physician's Global Assessment (PGA) for each of nine organ systems are given a weighted score and summed up if present at the time of the visit or in the preceding 10 days. The maximum theoretical score for the SELENA SLEDAI is 105 (all 24 descriptors present simultaneously) with 0 indicating inactive disease.
  • SLICC/ACR-DI Change From Baseline at Week 36 [ Time Frame: Baseline and Week 36 ]
    Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus (SLICC/ACR-DI) captures permanent changes which have occurred in patients with SLE, regardless of causality. The questionnaire contains 41 items covering 12 different organ systems. The score of items ranges from 1 to 3 and the total score from 0 to 47. By definition score 0 corresponds to diagnostics and damage over time can only be stable or increase, theoretically to a maximum of 47 points.
  • CLASI Total Activity Change From Baseline at Week 36 [ Time Frame: Baseline and Week 36 ]
    Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was specifically developed to assess the cutaneous manifestations of SLE. It measures both disease activity and permanent damage (e.g. dyspigmentation and scarring) over the entire body surface. CLASI total activity score ranges from 0 to 70, with higher scores indicating more severe skin disease.
  • Number of Participants Who Achieved a Composite SRI-4 Including CS ≤7,5mg/Day at Week 36 [ Time Frame: At Week 36 ]
    SRI (4) plus CS ≤ 7.5 mg/day responder was defined as a participant who had the following criteria at week 36:
    • reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and
    • no new BILAG A at week 36, and
    • no more than 1 new BILAG B at week 36, and
    • no deterioration in PGA (<10% worsening) on 100-mm VAS compared with baseline plus CS ≤7.5mg equivalent prednisolone per day at week 36
  • Number of Participants Who Achieved a Composite SRI-4 Including CS ≤5mg/Day at Week 36 [ Time Frame: At Week 36 ]
    SRI-4 plus CS ≤ 5mg/day responder was defined as a participant who had the following criteria at Week 36:
    • reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and
    • no new BILAG A at week 36, and
    • no more than 1 new BILAG B at week 36, and
    • no deterioration in PGA (<10% worsening) on 100-mm VAS compared with baseline plus corticosteroids (CS) ≤5mg equivalent prednisolone per day at week 36
  • Number of Participants With Neutralizing Anti-IFN-alpha Antibodies at W36 [ Time Frame: At week 36 ]
    Individual serum antibody neutralizing capacity against recombinant IFN-alpha2b was measured by reporter gene assay using Interferon Sensitive Response Element (ISRE) reporter.
  • Number of Participants With Treatment-related Adverse Events [ Time Frame: 9 months ]
    Number of participants who reported any treatment-related adverse events until month 9
Original Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2016)
  • Response to treatment with IFN-K, as measured by the SLE Responder Index (SRI)-4 response criteria at Week 36 [ Time Frame: 9 months ]
  • Number of Participants With Treatment-related Adverse Events [ Time Frame: 9 months ]
Current Other Pre-specified Outcome Measures
 (submitted: March 25, 2020)
CS Mean Daily Dose at W36 [ Time Frame: At W36 ]
mean daily dose of corticosteroid (CS) (prednisone equivalent)
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase IIb Study of IFN-K in Systemic Lupus Erythematosus
Official Title  ICMJE A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Neutralization of the Interferon Gene Signature and the Clinical Efficacy of IFNα-Kinoid in Adult Subjects With Systemic Lupus Erythematosus
Brief Summary

The safety and immunogenicity of the IFNα-Kinoid (IFN-K) have been evaluated in a phase I clinical study conducted in subjects with Systemic Lupus Erythematosus (SLE). Preliminary results showed acceptable safety profile and patients developped antibodies response.

The principal aim of the present study is to confirm the neutralization of the interferon gene signature and the clinical efficacy of IFN-K in subjects with SLE. In addition, the immune responses and the safety elicited by IFN-K will also be evaluated.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE
  • Biological: IFNα-Kinoid
  • Other: Placebo
  • Other: ISA 51 VG
Study Arms  ICMJE
  • Experimental: IFNα-Kinoid
    IFNα-Kinoid (IFN-K) adjuvanted with ISA 51 VG via intramuscular injection. 1 administration of 240 μg at W0, W1, W4 and 1 administration of 120 μg at month 3 (W12) and month 6 (W24) in addition to standard of care treatment.
    Interventions:
    • Biological: IFNα-Kinoid
    • Other: ISA 51 VG
  • Placebo Comparator: Placebo
    Placebo normal saline (0.9% Sodium Chloride) adjuvanted with ISA 51 VG via intramuscular injection. 1 administration of 240 μg at week (W)0, W1, W4 and 1 administration of 120 μg at month 3 (W12) and month 6 (W24) in addition to standard of care treatment.
    Interventions:
    • Other: Placebo
    • Other: ISA 51 VG
Publications * Houssiau FA, Thanou A, Mazur M, Ramiterre E, Gomez Mora DA, Misterska-Skora M, Perich-Campos RA, Smakotina SA, Cerpa Cruz S, Louzir B, Croughs T, Tee ML. IFN-α kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study. Ann Rheum Dis. 2020 Mar;79(3):347-355. doi: 10.1136/annrheumdis-2019-216379. Epub 2019 Dec 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 25, 2020)
185
Original Estimated Enrollment  ICMJE
 (submitted: January 22, 2016)
166
Actual Study Completion Date  ICMJE February 4, 2020
Actual Primary Completion Date March 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has had a diagnosis of SLE according to current American College of Rheumatology (ACR) criteria (4 of 11 ACR criteria)
  • Has SLEDAI-2K ≥ 6
  • Has at least 1 BILAG A and/or at least 2 BILAG B
  • Has a positive IFN gene signature by reverse transcription quantitative polymerase chain reaction (RT-qPCR)
  • Has anti-nuclear antibodies (ANA) ≥ 1:160 and/or anti-dsDNA antibodies ≥ 7.0 IU/mL
  • Currently receiving at least one treatment for SLE

Exclusion Criteria:

  • Has active, severe lupus nephritis as defined either by the immediate need for cyclophosphamide treatment or by renal BILAG A
  • Has active, severe, neuropsychiatric SLE, defined as neuropsychiatric BILAG A
  • Has been treated with corticosteroids (CS) at a dose of >20 mg of prednisone equivalent/day for > 7 consecutive days
  • Is currently receiving or has received pulse dose CS (≥ 250 mg prednisone equivalent/day)
  • Has received potent immunosuppressive drugs
  • Has received abatacept, sifalimumab, rontalizumab, anifrolumab, belimumab, tumor necrosis factor (TNF) antagonists or another registered or investigational biological therapy
  • Has received anti-B-cell therapy (e.g., rituximab, epratuzumab)
  • Has frequent recurrences of oral or genital herpes simplex lesions
  • Is at high risk of significant infection and/or has any current signs or symptoms of infection at entry or has received intravenous antibiotics
  • Has received any live vaccine
  • Has used any investigational or non-registered product or any investigational or non-registered vaccine
  • Is high-risk human papilloma virus (HPV) positive by rRT-qPCR on a cervical swab
  • Has cytological abnormalities ≥ high grade squamous intraepithelial lesions (HSIL) on a cervical swab
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   Chile,   Colombia,   Croatia,   France,   Georgia,   Germany,   Italy,   Korea, Republic of,   Mexico,   Moldova, Republic of,   Peru,   Philippines,   Poland,   Russian Federation,   Switzerland,   Taiwan,   Thailand,   Tunisia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02665364
Other Study ID Numbers  ICMJE IFN-K-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Neovacs
Study Sponsor  ICMJE Neovacs
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Frédéric Houssiau, MD, PhD Head of Rhumatology, UCL, Brussels, Belgium
PRS Account Neovacs
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP