Phase IIb Study of IFN-K in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02665364
• Other study ID #: IFN-K-002
• Status: Terminated
• Phase: Phase 2
• Start date: September 23, 2015
• Est. completion date: February 4, 2020

Study information

• Verified date: March 2020
• Source: Neovacs
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 185
• Est. completion date: February 4, 2020
• Est. primary completion date: March 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Biological:
• IFNa-Kinoid

Other:
• Placebo

• ISA 51 VG

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Belgium	Research Site	Bruxelles
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Bogota
Colombia	Research Site	Bucaramanga
Colombia	Research Site	Medellín	Antioquia
Colombia	Research Site	Zipaquira
Croatia	Research Site	Zagreb
France	Research Site	Lille
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Paris
France	Research Site	Pessac	Bordeaux
France	Research site	Strasbourg
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Germany	Research site	Bad-Nauheim
Germany	Research Site	Berlin
Germany	Research Site	Hannover
Germany	Research Site	Mainz
Germany	Research Site	Munich
Italy	Research Site	Bologna
Italy	Research Site	Milan
Italy	Research Site	Pavia
Italy	Research Site	Pisa
Italy	Research Site	Rome	Roma
Italy	Research Site	Verona
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Cuernavaca
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Leon
Mexico	Research Site	Mexico
Mexico	Research Site	Mexico
Moldova, Republic of	Research Site	Chisinau
Moldova, Republic of	Research Site	Chisinau
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Cebu
Philippines	Research Site	Davao
Philippines	Research Site	Manila
Philippines	Research Site	Quezon
Poland	Research Site	Bytom
Poland	Research Site	Krakow
Poland	Research Site	Poznan
Poland	Research Site	Sosnowiec
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Orenburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Yekaterinburg
Switzerland	Research Site	Lausanne
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Tunisia	Research Site	Sfax
Tunisia	Research Site	Sousse
Tunisia	Research Site	Sousse
Tunisia	Research Site	Tunis
Tunisia	Research Site	Tunis
United States	Research Site	Austin	Texas
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fort Myers	Florida
United States	Research Site	La Jolla	California
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Neovacs

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CS Mean Daily Dose at W36	mean daily dose of corticosteroid (CS) (prednisone equivalent)	At W36
Primary	Percent Change From Baseline in IFN Gene Signature at W36	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.	Baseline and Last Available Value (LVA) between week 24 and week 36
Primary	Number of Participants Who Achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) With Superimposed CS Tapering 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).	At Week 36
Secondary	Number of Participants Who Achieved a Systematic Lupus Erythematosus (SLE) Responder Index (SRI)-4 at Week 36	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	W36 (9 months)
Secondary	Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) 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	At Week 36
Secondary	BILAG Global Score Change From Baseline to 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.	Last Available Value (LVA) between week 24 and week 36
Secondary	SELENA-SLEDAI - Change From Baseline to 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.	Baseline and Week 36
Secondary	SLICC/ACR-DI Change From Baseline at 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.	Baseline and Week 36
Secondary	CLASI Total Activity Change From Baseline at 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.	Baseline and Week 36
Secondary	Number of Participants Who Achieved a Composite SRI-4 Including CS =7,5mg/Day 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	At Week 36
Secondary	Number of Participants Who Achieved a Composite SRI-4 Including CS =5mg/Day 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	At Week 36
Secondary	Number of Participants With Neutralizing Anti-IFN-alpha Antibodies at W36	Individual serum antibody neutralizing capacity against recombinant IFN-alpha2b was measured by reporter gene assay using Interferon Sensitive Response Element (ISRE) reporter.	At week 36
Secondary	Number of Participants With Treatment-related Adverse Events	Number of participants who reported any treatment-related adverse events until month 9	9 months