Lupus Erythematosus, Systemic
Conditions
Keywords
CC-220, Safety, Efficacy, Active Systemic Lupus Erythematosus
Brief summary
The purpose of this Phase 2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of an oral treatment regimen of CC-220 versus placebo in adult subjects with active systemic lupus erythematosus. Approximately 280 subjects with a documented diagnosis of SLE will be randomized 2:2:1:2 to receive CC-220 (0.45 mg QD, 0.3 mg QD or 0.15 mg QD) or identically appearing placebo.
Detailed description
The study consists of four phases: * 4-week Screening Phase * 24-week placebo-controlled phase Subjects will receive either 0.45 mg QD, 0.3 mg QD, 0.15 mg QD or placebo for the first 24 weeks of treatment. * 28-week active treatment phase At Week 24, all subjects on placebo will be re-randomized to active treatment. * 52-week long-term extension phase Subjects who complete the treatment phase may be eligible to roll over into a Long-term Extension of up to 52 weeks of treatment. * 4 - 12-week observational follow-up All subjects who complete 52 weeks of treatment or discontinue the study early will enter a post-treatment observation follow-up phase. The Observational Follow-up Phase will consist of one visit 4 weeks following cessation of study drug for all subjects with an additional 12-week Observational Follow-up visit for males only.
Interventions
DRUGCC-220
CC-220
OTHERPlacebo
Placebo QD PO
Sponsors
Celgene
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female 18 years of age or older at the time of signing the informed consent. * Have a diagnosis of SLE for at least 6 months prior to the Screening Visit and fulfill the 1997 update of the 1982 American College of Rheumatology (ACR) Classification Criteria for SLE at the Screening Visit. * A SLEDAI 2K score of ≥ 6 points, WITH at least 4 points being a clinical SLEDAI 2K score. The clinical score excludes points attributable to any urine or blood laboratory results including immunologic measures. * At the Baseline Visit, a clinical SLEDAI 2K score of ≥ 4 points. * Have at least one of the following positive antibodies associated with SLE per the central laboratory within the Screening Phase: * Positive antinuclear antibody (ANA) test at the central laboratory with a titer of 1:40 or greater, associated with a diagnosis of SLE, * Anti-dsDNA antibodies elevated to above normal * Anti-Smith (anti-Sm) antibody elevated to above normal * Females of childbearing potential must: Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. o Either commit to true abstinence from heterosexual contact or agree to use two forms of reliable contraception simultaneously. * Male subjects must: Practice true abstinence or agree to use a barrier contraception during sexual contact. All subjects must: * Understand that the IP could have potential teratogenic risk. * Agree to abstain from donating blood while taking IP and for 28 days following discontinuation of the IP. * Have been treated with at least one of the following SLE medications prior to the Screening Visit: antimalarials, immunosuppressants, and/or corticosteroids. * Currently receiving stable doses of at least one of the following medications: systemic corticosteroids, antimalarials, and/or immunosuppressants.
Exclusion criteria
* Received intra-articular, intralesional, subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6 weeks prior to the Baseline Visit. * Received any other biologic or non-biologic immunosuppressive agent within 2 months of 5 pharmacokinetic half-lives (whichever is longer) prior to the Baseline Visit. * Have severe lupus nephritis defined as: estimated glomerular filtration rate of \< 45 mL/1.73 m2 or proteinuria \> 2000 mg/day based on protein to creatinine ratio, or active lupus nephritis that may require 'induction' therapy * Have active, severe or unstable neuropsychiatric lupus disease within 6 months of the Screening Visit. * Have serologic tests consistent with infection with either hepatitis B or hepatitis C, and/or confirmed history of hepatitis B or hepatitis C infection. * Have history of congenital and/or acquired immunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus, etc). * Have active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, or any major episode of infection requiring hospitalization or treatment with intravenous or oral antibiotics within 4 weeks of the Screening Visit and at any time during the Screening Phase, up through the first dose of IP. * Have active tuberculosis or a history of latent or active tuberculosis * Have malignancy or history of malignancy, except for: * treated (eg, cured) basal cell or squamous cell in situ skin carcinomas * treated (eg, cured) cervical intraepithelial neoplasia Grade 1 and Grade 2 * treated (eg, cured) carcinoma in situ of the cervix with no evidence of recurrence within 5 years of the Screening Visit. * Have a diagnosis or history consistent with Antiphospholipid Syndrome or triple antiphospholipid positivity (ie, positive lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein). * Have history of arterial or venous thrombosis * Have history or current diagnosis of peripheral neuropathy (sensory or motor) ≥ Grade 2. * Have presence of active uveitis or any other ophthalmological finding that in the opinion of the Investigator is clinically significant. * Have other non-SLE driven inflammatory joint or skin disease or overlap syndromes as the primary disease. * Have clinically significant or unstable or uncontrolled acute or chronic disease not due to SLE * Does not meet required laboratory criteria. * Does not meet pre-specified periods for prohibited medications. * Pregnant or a breast-feeding female. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response | Week 24 | The primary objective is to evaluate the clinical efficacy of three doses of CC-220 (0.45 mg once per day \[QD\], 0.3 mg QD or 0.15 mg QD) compared to placebo, for the treatment of active systemic lupus erythematosus (SLE) using the SLE Responder Index at Week 24 Composite endpoint SRI(4), defined by the following criteria: - Reduction from Baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score and - No new one or more British Isles Lupus Assessment Group (BILAG) A or new (excludes A to B) 2 or more BILAG B items compared to Baseline using BILAG 2004 Index and - No worsening from Baseline defined by an increase of \< 0.30 points from Baseline on a Physician's Global Assessment (PGA) visual analog scale (VAS) from 0-3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10 | Week 24 | The CLASI Activity Score ranges from 0 to 70. To generate the activity score erythema is scored on a scale of 0 (absent) to 3 (dark red; purple/violaceous/crusted/hemorrhagic) and scale/hypertrophy are scored on a scale of 0 (absent) to 2 (verrucous/hypertrophic). Both the erythema and scale/hypertrophy scores are assessed in 13 different anatomical locations. In addition, the presence of mucous membrane lesions is scored on a scale of 0 (absent) to 1 (lesion or ulceration), the occurrence of recent hair loss is captured (1=yes; 0=no) and non-scarring alopecia is scored on a scale of 0 (absent) to 3 (focal or patchy in more than one quadrant). To calculate the activity score, all scores for erythema, scale/hypertrophy, mucous membrane lesions and alopecia are added together. |
| Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index | Week 24 | The BILAG 2004 is a composite index that is based on the Classic BILAG index. It is a clinical measure of lupus disease activity. This tool assesses the changing severity of clinical manifestations of SLE using an ordinal scale scoring system that contain 9 systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological). Activity in each organ system is scored as: A=most active disease; B=intermediate activity; C=mild, stable disease; D=previous involvement, currently inactive; E=no previous activity. |
| Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline | Week 24 | The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease. |
| Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline | Week 24 | Joint tenderness and swelling will be noted as present or absent, with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data. |
| Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline | Week 24 | Joint tenderness and swelling will be noted as present or absent, with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data. |
| Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline | Week 24 | The SLEDAI 2K score measures disease activity through assessment of 24 lupus manifestations using a weighted score of 1 to 8 points. A manifestation is recorded if it is present over the previous 30 days regardless of severity or whether it has improved or worsened. A SLEDAI 2K score of 3 to 4 points is representative of active disease and a decrease of 1 to 2 points is considered clinically meaningful. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | Week 24 | The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The total FACIT-Fatigue score ranges from 0 to 52. Note: Data presented is Adjusted mean data. |
| Percentage of Participants With Corticosteroid Reduction | Week 24 | \- The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to ≤ 7.5 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24 - The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to \< 10 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24 |
| Percent Change From Baseline in Corticosteroid Reduction | Week 24 | Percent change from Baseline in oral corticosteroid (OCS) dose in subjects with prednisone or equivalent ≥ 10 mg/day at Baseline Note: Data presented is Adjusted mean data. |
| The Total Corticosteroid Dose From Baseline Through Week 24 | Through Week 24 | Standardized total oral corticosteroid (OCS) dose. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | from first dose to 28 days post-last dose through Week 24 (placebo-controlled phase), approximately 28 weeks total | Number of participants who experienced a TEAE during the course of the study |
| Mean Change From Baseline in PGA Score | Week 24 | The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease. |
Countries
Argentina, Belgium, Brazil, Canada, Colombia, France, Germany, Hungary, Italy, Mexico, Poland, Russia, Serbia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PBO QD Placebo-matching treatment once a day. | 83 |
| 0.15 mg QD Participants dosed with CC-220 at 0.15 mg once a day | 42 |
| 0.30 mg QD Participants dosed with CC-220 at 0.30 mg once a day | 82 |
| 0.45 mg QD Participants dosed with CC-220 at 0.45 mg once a day | 82 |
| Total | 289 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Placebo Controlled Phase | Participant Withdrew Consent | 0 | 1 | 0 | 0 |
| Treatment Period | Adverse Event | 5 | 2 | 1 | 11 |
| Treatment Period | Death | 1 | 0 | 0 | 0 |
| Treatment Period | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Treatment Period | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Treatment Period | Other reasons | 1 | 1 | 0 | 0 |
| Treatment Period | Pregnancy | 1 | 0 | 0 | 0 |
| Treatment Period | Protocol Violation | 0 | 0 | 0 | 1 |
| Treatment Period | Withdrawal by Subject | 2 | 5 | 2 | 6 |
Baseline characteristics
| Characteristic | 0.30 mg QD | 0.45 mg QD | Total | PBO QD | 0.15 mg QD |
|---|---|---|---|---|---|
| Age, Customized >= 40 to <= 50 | 21 Participants | 28 Participants | 90 Participants | 26 Participants | 15 Participants |
| Age, Customized < 40 years old | 31 Participants | 25 Participants | 104 Participants | 33 Participants | 15 Participants |
| Age, Customized > 50 to < 65 | 24 Participants | 24 Participants | 77 Participants | 19 Participants | 10 Participants |
| Age, Customized >= 65 | 6 Participants | 5 Participants | 18 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants | 33 Participants | 141 Participants | 41 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 49 Participants | 148 Participants | 42 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 5 Participants | 13 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 5 Participants | 21 Participants | 7 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not collected or reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 15 Participants | 11 Participants | 45 Participants | 14 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 59 Participants | 61 Participants | 209 Participants | 60 Participants | 29 Participants |
| Sex: Female, Male Female | 77 Participants | 80 Participants | 279 Participants | 81 Participants | 41 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 10 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 42 | 0 / 82 | 0 / 81 | 1 / 83 | 1 / 36 | 0 / 36 |
| other Total, other adverse events | 32 / 42 | 63 / 82 | 62 / 81 | 34 / 83 | 16 / 36 | 26 / 36 |
| serious Total, serious adverse events | 6 / 42 | 10 / 82 | 14 / 81 | 7 / 83 | 2 / 36 | 3 / 36 |
Outcome results
Primary
Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response
The primary objective is to evaluate the clinical efficacy of three doses of CC-220 (0.45 mg once per day \[QD\], 0.3 mg QD or 0.15 mg QD) compared to placebo, for the treatment of active systemic lupus erythematosus (SLE) using the SLE Responder Index at Week 24 Composite endpoint SRI(4), defined by the following criteria: - Reduction from Baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score and - No new one or more British Isles Lupus Assessment Group (BILAG) A or new (excludes A to B) 2 or more BILAG B items compared to Baseline using BILAG 2004 Index and - No worsening from Baseline defined by an increase of \< 0.30 points from Baseline on a Physician's Global Assessment (PGA) visual analog scale (VAS) from 0-3
Time frame: Week 24
Population: Primary analysis based on Intent-to-treat (ITT) Population (all randomized participants who received at least one dose of investigational product) and nonresponder imputation (NRI). Participants with insufficient data for response determination at the given time point are considered nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBO QD | Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response | 29 Number of participants |
| 0.15 mg QD | Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response | 20 Number of participants |
| 0.30 mg QD | Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response | 33 Number of participants |
| 0.45 mg QD | Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response | 44 Number of participants |
p-value: 0.21495% CI: [-6.57, 29]Cochran-Mantel-Haenszel
p-value: 0.51295% CI: [-9.77, 19.48]Cochran-Mantel-Haenszel
p-value: 0.01195% CI: [4.12, 33.42]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The total FACIT-Fatigue score ranges from 0 to 52. Note: Data presented is Adjusted mean data.
Time frame: Week 24
Population: ITT population; participants with a baseline value and a value at the time point
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PBO QD | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | 3.8 scores on a scale |
| 0.15 mg QD | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | 2.7 scores on a scale |
| 0.30 mg QD | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | 3.1 scores on a scale |
| 0.45 mg QD | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | 5.2 scores on a scale |
p-value: 0.54695% CI: [-4.7, 2.5]longitudinal data analysis model
p-value: 0.68195% CI: [-3.7, 2.4]longitudinal data analysis model
p-value: 0.3595% CI: [-1.6, 4.4]longitudinal data analysis model
Secondary
Mean Change From Baseline in PGA Score
The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.
Time frame: Week 24
Population: ITT population with a baseline value and a value at the time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PBO QD | Mean Change From Baseline in PGA Score | -0.803 scores on a scale | Standard Deviation 0.605 |
| 0.15 mg QD | Mean Change From Baseline in PGA Score | -0.805 scores on a scale | Standard Deviation 0.528 |
| 0.30 mg QD | Mean Change From Baseline in PGA Score | -0.819 scores on a scale | Standard Deviation 0.629 |
| 0.45 mg QD | Mean Change From Baseline in PGA Score | -0.883 scores on a scale | Standard Deviation 0.546 |
Secondary
Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline
Joint tenderness and swelling will be noted as present or absent, with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data.
Time frame: Week 24
Population: ITT Population; Subjects with \>=2 Swollen Joints, with a baseline value and a value at the time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PBO QD | Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline | -6.7 swollen joints |
| 0.15 mg QD | Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline | -6.0 swollen joints |
| 0.30 mg QD | Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline | -6.0 swollen joints |
| 0.45 mg QD | Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline | -6.6 swollen joints |
p-value: 0.11695% CI: [-0.2, 1.5]longitudinal data analysis model
p-value: 0.09495% CI: [-0.1, 1.6]longitudinal data analysis model
p-value: 0.88195% CI: [-0.6, 0.8]longitudinal data analysis model
Secondary
Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline
Joint tenderness and swelling will be noted as present or absent, with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data.
Time frame: Week 24
Population: ITT Population; Participants with \>=2 Tender Joints, with a baseline value and a value at the time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PBO QD | Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline | -7.9 tender joints |
| 0.15 mg QD | Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline | -6.8 tender joints |
| 0.30 mg QD | Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline | -6.7 tender joints |
| 0.45 mg QD | Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline | -7.6 tender joints |
p-value: 0.1695% CI: [-0.4, 2.6]longitudinal data analysis model
p-value: 0.05695% CI: [0, 2.6]longitudinal data analysis model
p-value: 0.62195% CI: [-1, 1.6]longitudinal data analysis model
Secondary
Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10
The CLASI Activity Score ranges from 0 to 70. To generate the activity score erythema is scored on a scale of 0 (absent) to 3 (dark red; purple/violaceous/crusted/hemorrhagic) and scale/hypertrophy are scored on a scale of 0 (absent) to 2 (verrucous/hypertrophic). Both the erythema and scale/hypertrophy scores are assessed in 13 different anatomical locations. In addition, the presence of mucous membrane lesions is scored on a scale of 0 (absent) to 1 (lesion or ulceration), the occurrence of recent hair loss is captured (1=yes; 0=no) and non-scarring alopecia is scored on a scale of 0 (absent) to 3 (focal or patchy in more than one quadrant). To calculate the activity score, all scores for erythema, scale/hypertrophy, mucous membrane lesions and alopecia are added together.
Time frame: Week 24
Population: ITT population with Baseline CLASI activity score ≥ 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBO QD | Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10 | 8 Number of participants |
| 0.15 mg QD | Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10 | 8 Number of participants |
| 0.30 mg QD | Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10 | 8 Number of participants |
| 0.45 mg QD | Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10 | 13 Number of participants |
p-value: 0.44695% CI: [-12.38, 53.11]Cochran-Mantel-Haenszel
p-value: >0.99995% CI: [-27.64, 39.38]Cochran-Mantel-Haenszel
p-value: 0.48895% CI: [-19.54, 44.48]Cochran-Mantel-Haenszel
Secondary
Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index
The BILAG 2004 is a composite index that is based on the Classic BILAG index. It is a clinical measure of lupus disease activity. This tool assesses the changing severity of clinical manifestations of SLE using an ordinal scale scoring system that contain 9 systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological). Activity in each organ system is scored as: A=most active disease; B=intermediate activity; C=mild, stable disease; D=previous involvement, currently inactive; E=no previous activity.
Time frame: Week 24
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBO QD | Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index | 65 Number of participants |
| 0.15 mg QD | Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index | 38 Number of participants |
| 0.30 mg QD | Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index | 59 Number of participants |
| 0.45 mg QD | Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index | 70 Number of participants |
p-value: 0.09295% CI: [-2.74, 24.07]Cochran-Mantel-Haenszel
p-value: 0.43495% CI: [-18.43, 8.06]Cochran-Mantel-Haenszel
p-value: 0.18295% CI: [-3.88, 19.65]Cochran-Mantel-Haenszel
Secondary
Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline
The SLEDAI 2K score measures disease activity through assessment of 24 lupus manifestations using a weighted score of 1 to 8 points. A manifestation is recorded if it is present over the previous 30 days regardless of severity or whether it has improved or worsened. A SLEDAI 2K score of 3 to 4 points is representative of active disease and a decrease of 1 to 2 points is considered clinically meaningful.
Time frame: Week 24
Population: ITT population. Participants with insufficient data for response determination at the given time point are considered nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBO QD | Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline | 30 Number of participants |
| 0.15 mg QD | Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline | 20 Number of participants |
| 0.30 mg QD | Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline | 35 Number of participants |
| 0.45 mg QD | Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline | 45 Number of participants |
p-value: 0.26495% CI: [-7.66, 27.97]Cochran-Mantel-Haenszel
p-value: 0.39995% CI: [-8.45, 21]Cochran-Mantel-Haenszel
p-value: 0.01295% CI: [4.01, 33.36]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Number of participants who experienced a TEAE during the course of the study
Time frame: from first dose to 28 days post-last dose through Week 24 (placebo-controlled phase), approximately 28 weeks total
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PBO QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 54 Number of participants |
| PBO QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Drug Withdrawal | 6 Number of participants |
| PBO QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Drug Interruption | 15 Number of participants |
| PBO QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Drug-related TEAE | 24 Number of participants |
| PBO QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Death | 1 Number of participants |
| PBO QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Serious TEAE | 7 Number of participants |
| PBO QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Severe TEAE | 5 Number of participants |
| 0.15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Drug Withdrawal | 2 Number of participants |
| 0.15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Severe TEAE | 3 Number of participants |
| 0.15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Serious TEAE | 3 Number of participants |
| 0.15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Drug Interruption | 10 Number of participants |
| 0.15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Death | 0 Number of participants |
| 0.15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Drug-related TEAE | 14 Number of participants |
| 0.15 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 31 Number of participants |
| 0.30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Severe TEAE | 4 Number of participants |
| 0.30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 64 Number of participants |
| 0.30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Drug-related TEAE | 36 Number of participants |
| 0.30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Serious TEAE | 4 Number of participants |
| 0.30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Drug Interruption | 14 Number of participants |
| 0.30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Drug Withdrawal | 11 Number of participants |
| 0.30 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Death | 0 Number of participants |
| 0.45 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Serious TEAE | 6 Number of participants |
| 0.45 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Death | 0 Number of participants |
| 0.45 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Drug Withdrawal | 4 Number of participants |
| 0.45 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Drug-related TEAE | 32 Number of participants |
| 0.45 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 63 Number of participants |
| 0.45 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Drug Interruption | 23 Number of participants |
| 0.45 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Severe TEAE | 1 Number of participants |
Secondary
Percentage of Participants With Corticosteroid Reduction
\- The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to ≤ 7.5 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24 - The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to \< 10 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24
Time frame: Week 24
Population: ITT Population; Participants with Baseline OCS Dose \>= 10 mg/day Participants with insufficient data for response determination at the given time point are considered nonresponders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PBO QD | Percentage of Participants With Corticosteroid Reduction | Week 24, <= 7.5 mg/day | 3.2 Percentage of participants |
| PBO QD | Percentage of Participants With Corticosteroid Reduction | Week 24, < 10 mg/day | 6.5 Percentage of participants |
| 0.15 mg QD | Percentage of Participants With Corticosteroid Reduction | Week 24, < 10 mg/day | 0.0 Percentage of participants |
| 0.15 mg QD | Percentage of Participants With Corticosteroid Reduction | Week 24, <= 7.5 mg/day | 0.0 Percentage of participants |
| 0.30 mg QD | Percentage of Participants With Corticosteroid Reduction | Week 24, <= 7.5 mg/day | 3.3 Percentage of participants |
| 0.30 mg QD | Percentage of Participants With Corticosteroid Reduction | Week 24, < 10 mg/day | 3.3 Percentage of participants |
| 0.45 mg QD | Percentage of Participants With Corticosteroid Reduction | Week 24, <= 7.5 mg/day | 0.0 Percentage of participants |
| 0.45 mg QD | Percentage of Participants With Corticosteroid Reduction | Week 24, < 10 mg/day | 0.0 Percentage of participants |
p-value: >0.99995% CI: [-15.13, 15.91]longitudinal data analysis model
p-value: >0.99995% CI: [-17.74, 13]longitudinal data analysis model
Secondary
Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline
The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.
Time frame: Week 24
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBO QD | Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline | 78.3 Percentage of participants |
| 0.15 mg QD | Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline | 90.5 Percentage of participants |
| 0.30 mg QD | Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline | 73.2 Percentage of participants |
| 0.45 mg QD | Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline | 85.2 Percentage of participants |
p-value: 0.09895% CI: [-2.98, 23.78]Cochran-Mantel-Haenszel
p-value: 0.52195% CI: [-17.36, 8.92]Cochran-Mantel-Haenszel
p-value: 0.26795% CI: [-5.24, 18.55]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Corticosteroid Reduction
Percent change from Baseline in oral corticosteroid (OCS) dose in subjects with prednisone or equivalent ≥ 10 mg/day at Baseline Note: Data presented is Adjusted mean data.
Time frame: Week 24
Population: ITT Population; Participants with the Baseline OCS Dose \>= 10 mg/day, with a baseline value and a value at the time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PBO QD | Percent Change From Baseline in Corticosteroid Reduction | -7.9 percent change from baseline |
| 0.15 mg QD | Percent Change From Baseline in Corticosteroid Reduction | -5.1 percent change from baseline |
| 0.30 mg QD | Percent Change From Baseline in Corticosteroid Reduction | -3.8 percent change from baseline |
| 0.45 mg QD | Percent Change From Baseline in Corticosteroid Reduction | -1.4 percent change from baseline |
p-value: 0.53595% CI: [-6, 11.6]longitudinal data analysis model
p-value: 0.30995% CI: [-3.9, 12.2]longitudinal data analysis model
p-value: 0.09195% CI: [-1, 14.1]longitudinal data analysis model
Secondary
The Total Corticosteroid Dose From Baseline Through Week 24
Standardized total oral corticosteroid (OCS) dose.
Time frame: Through Week 24
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PBO QD | The Total Corticosteroid Dose From Baseline Through Week 24 | 1139.7 mg | Standard Deviation 916.9 |
| 0.15 mg QD | The Total Corticosteroid Dose From Baseline Through Week 24 | 1101.9 mg | Standard Deviation 827.1 |
| 0.30 mg QD | The Total Corticosteroid Dose From Baseline Through Week 24 | 1071.8 mg | Standard Deviation 965 |
| 0.45 mg QD | The Total Corticosteroid Dose From Baseline Through Week 24 | 1105.5 mg | Standard Deviation 969.3 |