Systemic Lupus Erythematosus
Conditions
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.
Interventions
BIOLOGICALIFNα-Kinoid
OTHERPlacebo
OTHERISA 51 VG
Sponsors
Neovacs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) With Superimposed CS Tapering at Week 36 | 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). |
| Percent Change From Baseline in IFN Gene Signature at W36 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) at Week 36 | 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 | 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 | 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 | 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. |
| Number of Participants Who Achieved a Composite SRI-4 Including CS ≤7,5mg/Day at Week 36 | 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 | 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 | 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 | 9 months | Number of participants who reported any treatment-related adverse events until month 9 |
| CLASI Total Activity Change From Baseline at Week 36 | 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 Systematic Lupus Erythematosus (SLE) Responder Index (SRI)-4 at Week 36 | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| CS Mean Daily Dose at W36 | At W36 | mean daily dose of corticosteroid (CS) (prednisone equivalent) |
Countries
Argentina, Belgium, Chile, Colombia, Croatia, France, Georgia, Germany, Italy, Mexico, Moldova, Peru, Philippines, Poland, Russia, South Korea, Switzerland, Taiwan, Thailand, Tunisia, United States
Participant flow
Pre-assignment details
The number of participants enrolled is the number of participants who signed informed condent form. One subject was randomized in IFN-K group and did not receive IFN-K. A total of 185 subjects were randomized and 184 subjects were treated : 91 subjects received IFN-K and 93 subjects received placebo.
Participants by arm
| Arm | Count |
|---|---|
| IFN-Kinoid IFN-K adjuvanted with ISA 51 VG | 91 |
| Placebo Placebo adjuvanted with ISA 51 VG | 93 |
| Total | 184 |
Baseline characteristics
| Characteristic | Placebo | Total | IFN-Kinoid |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 93 Participants | 184 Participants | 91 Participants |
| Race/Ethnicity, Customized Eyhnic origin Asian | 10 Participants | 26 Participants | 16 Participants |
| Race/Ethnicity, Customized Eyhnic origin Black | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Eyhnic origin Caucasian/Hispanic | 72 Participants | 140 Participants | 68 Participants |
| Race/Ethnicity, Customized Eyhnic origin Other | 10 Participants | 16 Participants | 6 Participants |
| Region of Enrollment Argentina | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Belgium | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Chile | 4 participants | 6 participants | 2 participants |
| Region of Enrollment Colombia | 9 participants | 18 participants | 9 participants |
| Region of Enrollment Croatia | 1 participants | 2 participants | 1 participants |
| Region of Enrollment France | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Georgia | 3 participants | 5 participants | 2 participants |
| Region of Enrollment Germany | 2 participants | 4 participants | 2 participants |
| Region of Enrollment Italy | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Mexico | 9 participants | 19 participants | 10 participants |
| Region of Enrollment Moldova | 14 participants | 20 participants | 6 participants |
| Region of Enrollment Peru | 11 participants | 21 participants | 10 participants |
| Region of Enrollment Philippines | 9 participants | 19 participants | 10 participants |
| Region of Enrollment Poland | 5 participants | 18 participants | 13 participants |
| Region of Enrollment Russia | 13 participants | 22 participants | 9 participants |
| Region of Enrollment South Korea | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Taiwan | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Thailand | 0 participants | 3 participants | 3 participants |
| Region of Enrollment Tunisia | 4 participants | 9 participants | 5 participants |
| Region of Enrollment United States | 4 participants | 6 participants | 2 participants |
| Sex: Female, Male Female | 88 Participants | 172 Participants | 84 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 91 | 1 / 93 |
| other Total, other adverse events | 75 / 91 | 71 / 93 |
| serious Total, serious adverse events | 6 / 91 | 12 / 93 |
Outcome results
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).
Time frame: At Week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 85 completed Week 36 visit. 93 subjects received placebo, among them, 84 completed Week 36 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants Who Achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) With Superimposed CS Tapering at Week 36 | 35 Participants |
| Placebo | Number of Participants Who Achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) With Superimposed CS Tapering at Week 36 | 29 Participants |
Comparison: Descriptive statistics for the response to treatment according to BICLA at week 36 were presented by treatment group. The response to treatment according to BICLA was analyzed using a logistic regression with the response rate as dependent variable and treatment as independent variable, while adjusting for the minimization factors used for randomization.p-value: 0.3495% CI: [0.716, 2.657]Regression, Logistic
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.
Time frame: Baseline and Last Available Value (LVA) between week 24 and week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 87 had a Last available value (LAV) between Week 24 and Week 36 analyzed. 93 subjects received placebo, among them, 84 had LAV between Week 24 and Week 36 analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFN-K | Percent Change From Baseline in IFN Gene Signature at W36 | -31.04 percent change | Standard Deviation 38.96 |
| Placebo | Percent Change From Baseline in IFN Gene Signature at W36 | -0.44 percent change | Standard Deviation 27.34 |
Comparison: The percent of change from baseline to last available value between W24 and W36 of treatment in the expression of IFN-induced genes was analyzed using an analysis of covariance (ANCOVA) model.p-value: <0.000195% CI: [-40.6653, -19.8951]ANCOVA
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.
Time frame: Last Available Value (LVA) between week 24 and week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 87 had a Last available value (LAV) between Week 24 and Week 36 analyzed. 93 subjects received placebo, among them, 84 had LAV between Week 24 and Week 36 analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFN-K | BILAG Global Score Change From Baseline to Last Available Value (LVA) Between Week 24 and Week 36 | -11.43 scores on a scale | Standard Deviation 8.57 |
| Placebo | BILAG Global Score Change From Baseline to Last Available Value (LVA) Between Week 24 and Week 36 | -10.76 scores on a scale | Standard Deviation 7.84 |
Comparison: Baseline to last available value between W24 and W36p-value: 0.7946Wilcoxon (Mann-Whitney)
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.
Time frame: Baseline and Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFN-K | CLASI Total Activity Change From Baseline at Week 36 | -3.22 scores on a scale | Standard Deviation 5.94 |
| Placebo | CLASI Total Activity Change From Baseline at Week 36 | -2.85 scores on a scale | Standard Deviation 3.6 |
p-value: 0.6169Student - Satterthwaite
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
Time frame: At Week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 79 had CS ≤5mg/day at Week 36 visit. 93 subjects received placebo, among them, 77 had CS ≤5mg/day at Week 36 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants Who Achieved a Composite SRI-4 Including CS ≤5mg/Day at Week 36 | 43 Participants |
| Placebo | Number of Participants Who Achieved a Composite SRI-4 Including CS ≤5mg/Day at Week 36 | 30 Participants |
p-value: 0.076295% CI: [0.938, 3.574]Regression, Logistic
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
Time frame: At Week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 79 had CS ≤7,5mg/day at Week 36 visit. 93 subjects received placebo, among them, 77 had CS ≤7,5mg/day at Week 36 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants Who Achieved a Composite SRI-4 Including CS ≤7,5mg/Day at Week 36 | 46 Participants |
| Placebo | Number of Participants Who Achieved a Composite SRI-4 Including CS ≤7,5mg/Day at Week 36 | 33 Participants |
p-value: 0.079695% CI: [0.932, 3.524]Regression, Logistic
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
Time frame: At Week 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) at Week 36 | 45 Participants |
| Placebo | Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) at Week 36 | 25 Participants |
p-value: 0.0022Pearson's Chi-squared
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
Time frame: W36 (9 months)
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 84 completed Week 36 visit. 93 subjects received placebo, among them, 83 completed Week 36 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants Who Achieved a Systematic Lupus Erythematosus (SLE) Responder Index (SRI)-4 at Week 36 | 57 Participants |
| Placebo | Number of Participants Who Achieved a Systematic Lupus Erythematosus (SLE) Responder Index (SRI)-4 at Week 36 | 54 Participants |
Comparison: The SRI-4 response was analyzed using a logistic regression using the response rate as dependent variable and treatment as independent variable, while adjusting for the minimization factors used for randomization.p-value: 0.624395% CI: [0.602, 2.329]Regression, Logistic
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.
Time frame: At week 36
Population: 91 subjects received IFN-K, among them, 79 were positive for Anti-IFN-alpha antibodies at Week 36 visit.~No Neutralizing Anti-IFN-alpha antibodies were performed on placebo subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants With Neutralizing Anti-IFN-alpha Antibodies at W36 | 72 Participants |
| Placebo | Number of Participants With Neutralizing Anti-IFN-alpha Antibodies at W36 | 0 Participants |
Secondary
Number of Participants With Treatment-related Adverse Events
Number of participants who reported any treatment-related adverse events until month 9
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants With Treatment-related Adverse Events | 75 Participants |
| Placebo | Number of Participants With Treatment-related Adverse Events | 71 Participants |
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.
Time frame: Baseline and Week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 84 completed Week 36 visit. 93 subjects received placebo, among them, 83 completed Week 36 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFN-K | SELENA-SLEDAI - Change From Baseline to Week 36 | -5.48 SELENA SLEDAI Score | Standard Deviation 4.3 |
| Placebo | SELENA-SLEDAI - Change From Baseline to Week 36 | -5.54 SELENA SLEDAI Score | Standard Deviation 4.44 |
p-value: 0.9224student - pooled
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.
Time frame: Baseline and Week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 82 completed SLICC/ACR/DI questionnaire at Week 36 visit. 93 subjects received placebo, among them, 83 completed Week 36 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFN-K | SLICC/ACR-DI Change From Baseline at Week 36 | -0.09 scores on a scale | Standard Deviation 0.59 |
| Placebo | SLICC/ACR-DI Change From Baseline at Week 36 | -0.17 scores on a scale | Standard Deviation 0.49 |
p-value: 0.3258student - pooled
Other Pre-specified
CS Mean Daily Dose at W36
mean daily dose of corticosteroid (CS) (prednisone equivalent)
Time frame: At W36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFN-K | CS Mean Daily Dose at W36 | 5.42 mg/day | Standard Error 3.28 |
| Placebo | CS Mean Daily Dose at W36 | 7.06 mg/day | Standard Error 4.69 |
p-value: 0.0097Student - Satterthwaite
Post Hoc
Number of Participants Who Achieved a Composite SRI-4 (CS ≤5mg/Day) Excluding IFN-K Subjects Without Positive Anti-IFNalpha Neutralizing Antibodies at Week 36
Subjects who had the following criteria defined as : SRI-4 plus CS ≤5mg/day -excluding IFN-K subjects without positive anti-IFN-alpha neutralizing antibodies
Time frame: At week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 72 had a Composite SRI-4 (CS ≤5mg/day) at Week 36 visit. 93 subjects received placebo, among them, 77 had a Composite SRI-4 CS ≤5mg/day at Week 36 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants Who Achieved a Composite SRI-4 (CS ≤5mg/Day) Excluding IFN-K Subjects Without Positive Anti-IFNalpha Neutralizing Antibodies at Week 36 | 40 Participants |
| Placebo | Number of Participants Who Achieved a Composite SRI-4 (CS ≤5mg/Day) Excluding IFN-K Subjects Without Positive Anti-IFNalpha Neutralizing Antibodies at Week 36 | 30 Participants |
p-value: 0.0425Pearson's Chi-squared
Post Hoc
Number of Participants Who Achieved a Composite SRI-4 (CS ≤7.5mg/Day) Excluding IFN-K Subjects Without Positive Anti-IFNalpha Neutralizing Antibodies at Week 36
participant who had the following criteria defined as : SRI-4 plus CS ≤7.5mg/day -excluding IFN-K Patients without positive anti-IFN-alpha neutralizing antibodies
Time frame: At week 36
Population: A total of 185 subjects were randomized and 184 were treated. 91 subjects received IFN-K, among them, 72 had a Composite SRI-4 (CS ≤7.5mg/day) at Week 36 visit. 93 subjects received placebo, among them, 77 had a Composite SRI-4 (CS ≤7.5mg/day) at Week 36 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN-K | Number of Participants Who Achieved a Composite SRI-4 (CS ≤7.5mg/Day) Excluding IFN-K Subjects Without Positive Anti-IFNalpha Neutralizing Antibodies at Week 36 | 43 Participants |
| Placebo | Number of Participants Who Achieved a Composite SRI-4 (CS ≤7.5mg/Day) Excluding IFN-K Subjects Without Positive Anti-IFNalpha Neutralizing Antibodies at Week 36 | 33 Participants |
p-value: 0.0396Pearson's Chi-squared