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Submitted by: Pearly Anne Cheng 2018-02-07 00:00:00 Last Updated by: Pearly Anne Cheng 2019-08-02 09:52:04


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

PHRR180208-001791

IFN-K-002:Phase IIb study of IFN-K In Systemic Lupus Erythermatosus

2015-CT0309

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

This will be a Phase IIb, randomized, double-blind, placebo-controlled multicenter study.

Study patients will be enrolled into one of the two treatment groups and
allocated in a 1:1 randomization ratio to receive IFN-K or placebo as outlined
below:
 Group 1: IFN-K emulsified in ISA 51 VG
 Group 2: placebo emulsified in ISA 51 VG
A total of 178 patients (89 patients in each group) will be enrolled.
The main study is comprised of 12 visits occurring over a period of 40 weeks.
The main study will be divided into four periods: a 4-week Screening Period
that will be performed to determine eligibility of the patients for randomization
into the study, a 12-week Induction Period, a 12-week Maintenance Period
and a 12-week Follow-up Period.
Study patients will then enter in an Extended Follow-up study period for a
duration of additional 240 weeks (60 months).

The total duration of the study will be 69 months (276 weeks).

Start Date Duration in Months Target Completion Date Actual Completion Date
2016-02-29 69 2021-11-29 0000-00-00

Ongoing

Institution Classification Region LTO #
Neovacs SA Private Business France 3000002140826
Institution Classification Region LTO #
Novotech (Australia) Pty. Ltd. - Philippine Branch Private Business NCR 3000002140826
Institution Region
Medical Center Manila NCR
Chong Hua Hospital Region VII
St. Luke's Medical Center - Quezon City NCR
Southern Philippines Medical Center Region XI
Name E-Mail Institution and Institution Address
Jennifer Arellano Jenny.Arellano@novotech-cro.com Unit A & D, 5th Floor, Rockwell Business Tower 1, Rockwell Business Center, Ortigas Avenue, Barangay Ugong, Pasig Metro Manila 1604 Philippines
Name E-Mail Institution and Institution Address
Jennifer Arellano Jenny.Arellano@novotech-cro.com Unit A & D, 5th Floor, Rockwell Business Tower 1, Rockwell Business Center, Ortigas Avenue, Barangay Ugong, Pasig Metro Manila 1604 Philippines
Name Expertise Affiliation
Edgar Ramiterre, MD Rheumatologist Southern Philippines Medical Center
James Bermas, MD Rheumatologist Chong Hua Hospital
Juan Javier T. Lichauco, MD Rheumatologist St. Luke's Medical Center - Quezon City
Michael L. Tee, MD Rheumatologist Medical Center Manila
Project Location Institutional Ethics Review Board
Southern Philippines Medical Center DOH XI Cluster Ethics Review Committee
Chong Hua Hospital Chong Hua Hospital Institutional Review Board
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board
Medical Center Manila Manila Medical Ethics Review Committee

Systemic Lupus Erythematosus

The primary objective of this study is to evaluate the neutralization of the IFN
gene signature following treatment with IFN-K, as measured by the change
from baseline of the expression of IFN-induced genes and to evaluate the
efficacy of treatment with IFN-K using the British Isles Lupus Assessment
Group (BILAG)-based Composite Lupus Assessment (BICLA) response
criteria.
The study will be considered as positive if a statistically significant better
effect of IFN-K compared to placebo is observed on the neutralization of the
IFN gene signature and if at least a trend favoring IFN-K is observed on the
BICLA response.

Unspecified

Completed

  • Argentina
  • Belgium
  • Chile
  • Croatia
  • France
  • Georgia
  • Germany
  • Italy
  • Mexico
  • Peru
  • Philippines
  • Poland
  • Russia
  • South Korea
  • Switzerland
  • Taiwan
  • Thailand

Clinical Trial

IFN-K-002:Phase IIb study of IFN-K In Systemic Lupus Erythermatosus

Unspecified

2015-10-28

0000-00-00

14

20

Competitive recruitment ( Recruitment Closed - Global)

29 Feb 2016

A patient meeting all of the following inclusion criteria at screening will be
eligible for participation in the study:
1. Has had a diagnosis of SLE according to current ACR criteria (4 of 11
ACR criteria)
2. Has SLEDAI-2K ≥ 6
3. Has at least 1 BILAG A and/or at least 2 BILAG B
4. Has a positive IFN gene signature by RT-qPCR as assessed on a limited
number of genes
5. Has anti-nuclear antibodies (ANA) ≥ 1:160 and/or anti-dsDNA
antibodies ≥ 7.0 IU/mL
6. Be a male or female, aged between 18 and 65 years, inclusive, at the
time of the screening visit
7. Agrees to receive influenza vaccination during each influenza season
of the study period
8. Currently receiving at least one of the following treatment:
 Corticosteroids (CS) at a dose of ≤ 20 mg of prednisone
equivalent/day
 Antimalarial drugs (hydroxychloroquine [HCQ] or chloroquine
[CQ]); the patient must have been treated since at least 8 weeks and
on stable dose for at least 4 weeks prior to first planned
administration of the study product
 Methotrexate (MTX); the patient must have been treated and be on
stable dose (≤ 20 mg/week) for at least 12 weeks prior to the first
planned administration of the study product
 Azathioprine (AZA); the patient must have been treated and be on
stable dose (≤ 2.5 mg/kg/day) for at least 12 weeks prior to the first
planned administration of the study product
 Mycophenolate mofetil (MMF), the patient must have been treated
and be on stable dose (≤ 2 g/day) for at least 12 weeks prior to the
first planned administration of the study product
9. Study patient and his/her partner has to use effective method of
contraception for the duration of the study including the Extended
Follow-up Period.
Note: If of child-bearing potential, effective contraception methods
include:
 Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least 6 weeks prior to the first planned
administration of the study product. In case of oophorectomy alone, the
reproductive status of the woman must be confirmed by follow up hormone level
assessment.
 Male sterilization (at least 6 months prior to Screening).
 Combination of the following:
          Oral, injected or implanted hormonal methods of contraception or other
              forms of hormonal contraception that have comparable efficacy (failure
              rate <1%), for example hormone vaginal ring or transdermal hormone
              contraception or
         Placement of an intrauterine device (IUD) or intrauterine system (IUS)
         And Barrier methods of contraception: condom or occlusive cap
            (diaphragm or cervical/vault caps) with spermicidal
             foam/gel/film/cream/vaginal suppository
        Women are considered post-menopausal and not of child bearing potential if they have
        had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
       (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
       oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In
       the case of oophorectomy alone, she is considered not of child bearing potential only
       when the reproductive status of the woman has been confirmed by follow up hormone
        level assessment.
10. Is able and willing to comply with the requirements of the study
protocol (e.g., completion of the diary cards, return for follow-up
visits), in the opinion of the Investigator
11. Has provided written informed consent


Interventional

INF-K-002/Placebo

Neovacs has prepared an adjuvanted interferon (IFN)α-kinoid (IFN-K)
formulation to induce polyclonal anti-IFNα antibodies.
In a Phase I-II, randomized, double-blind, placebo-controlled dose escalation
study, IFN-K has been evaluated in patients with mild to moderate Systemic
Lupus Erythematosus (SLE). The kinoid was generally well tolerated; few
local (including tenderness, swelling, erythema and itching) or systemic
reactions were reported, and were mild to moderate in severity and transient
in nature. The safety profile was considered acceptable by independent boards
of experts.
At baseline, patients were subdivided in two subgroups based on the
expression of SLE and IFN related genes. Patients with a high gene
expression, i.e. with a high IFN gene signature, accounted for two thirds of the
patients and their biological markers of disease (anti-double-stranded DNA
[dsDNA] antibodies, C3 and C4 levels) indicated a more active disease than
patients with a low IFN gene signature.
All patients developed an antibody response against IFNα, and antibody levels
were significantly higher in patients with a positive IFN gene signature than
in patients with a negative signature. In addition, 3out of 6 patients and 4 out
of 5 patients immunized with 120 mcg and 240 mcg, respectively, developed
neutralizing antibodies. Furthermore, IFNα-mediated and SLE-associated
gene expression was more reduced in patients immunized with IFN-K than in
patients treated with the placebo. This decrease in the expression of SLEassociated
genes significantly correlated with anti-IFNα antibody levels and
was more pronounced in patients with the highest IFN gene signature before
immunization. Furthermore, the increase in C3 complement from baseline
significantly correlated with the anti-IFNα antibody level

None

Randomized

Double Blind

Unspecified

Parallel

Primary Objective
The primary objective of this study is to evaluate the neutralization of the IFN
gene signature following treatment with IFN-K, as measured by the change
from baseline of the expression of IFN-induced genes and to evaluate the
efficacy of treatment with IFN-K using the British Isles Lupus Assessment
Group (BILAG)-based Composite Lupus Assessment (BICLA) response
criteria.
The study will be considered as positive if a statistically significant better
effect of IFN-K compared to placebo is observed on the neutralization of the
IFN gene signature and if at least a trend favoring IFN-K is observed on the
BICLA response.
Secondary Objectives
The secondary objectives of this study are:
 To evaluate the efficacy of treatment with IFN-K using:
 The SLE Responder Index [(SRI)-4 and above]
 The SLE Disease Activity Index-2000 (SLEDAI-2K)
 The BILAG-2004 index
 The Safety of Estrogen in Lupus Erythematosus National
Assessment-SLEDAI (SELENA-SLEDAI) Flare index
 The Systemic Lupus International Collaborating
Clinics/American College of Rheumatology-Damage Index for
Systemic Lupus Erythematosus (SLICC/ACR DI)
 The Cutaneous Lupus Erythematosus Disease Area and Severity
Index (CLASI) in patients with cutaneous lesions at baseline
 To evaluate the immune response induced by IFN-K
 Anti-IFNα antibody response
 Anti-Keyhole Limpet Hemocyanin (KLH) antibody response
 Anti-IFNα antibody neutralizing capacities
 To assess the safety of IFN-K emulsified with ISA 51 VG
Exploratory Objectives
The exploratory objectives of this study are:
 To assess disease activity using:
 The Physician’s Global Assessment (PGA) score
 The 28-Tender and Swollen joint counts
 A Joint Pain Visual Analog Scale (VAS)
 The flare description
 The changes in Lupus therapy
 To assess quality of life using:
 The Short Form (SF)-36 questionnaire
 The Functional Assessment of Chronic Illness Therapy (FACIT)
fatigue score
 To assess biological parameters:
 Levels of lupus related serum auto-antibodies and biomarkers
 Neutralizing capacity against IFN subtypes
 Anti-IFNα and Anti-KLH antibody isotyping
 IFN cross-neutralization
 Antibody response to influenza vaccination
 To assess correlations between immune responses, IFN gene signature and
clinical responses

Phase II

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