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

Registry ID

PHRR180208-001791

Secondary Identification Number

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

FDA Clinical Trial Reference (CTR) Number

2015-CT0309

Scientific Title

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

Project Description

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).

Project Duration

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

Project Status

Terminated

Reason for project pending/suspension/termination

Sponsor terminated the study because of lack of Funds

Implementing Agency (Primary Sponsor)

Institution	Classification	Region	LTO #
Neovacs SA	Private Business	France	3000002140826

Cooperating Agency (Secondary Sponsor)

Institution	Classification	Region	LTO #
Novotech (Australia) Pty. Ltd. - Philippine Branch	Private Business	NCR	3000002140826

Funding Agency (Sources of Monetary or Material Support)

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

Contact for Public Queries

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

Contact for Scientific Queries

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

Investigating Team

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 and Institutional Ethics Review Board

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

Health Condition(s) or Problem(s) Studied

Systemic Lupus Erythematosus

Primary Outcomes

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.

Key Secondary Outcomes

Unspecified

Recruitment Status

Completed

Countries of Recruitment

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

Research Classification

Clinical Trial

FDA Document Tracking Number

Unspecified

FDA Approval Date

2015-10-28

ERC Approval Date

0000-00-00

Target Sample Size (Philippines)

Actual Sample Size (Philippines)

Reason for the difference between Target & Actual Sample Sizes

Competitive recruitment ( Recruitment Closed - Global)

Date of First Enrollment

29 Feb 2016

Key Inclusion and Exlusion Criteria (CT)

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

Study Type

Interventional

Intervention Name

INF-K-002/Placebo

Intervention Description

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

Amendment Approval Date/Reasons

None

Method of Allocation

Randomized

Masking / Blinding

Double Blind

Masking Details

Unspecified

Assignment

Parallel

Purpose

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

Phase II

Research Utilization

Utilization	Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others