Systemic Lupus Erythematosus, SLE, Lupus
Conditions
Keywords
Systemic lupus erythematosus, SLE, Vitamin D3, Vitamin D deficiency, IFN alpha expression
Brief summary
The purpose of this study is to explore the impact of vitamin D3 on the expression of alpha interferon (IFN alpha) expression in systemic lupus erythematosus (SLE) patients with vitamin D deficiency.
Detailed description
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies with subsequent immune complex deposition and tissue inflammation. The role of interferon (IFN) alpha in the development of SLE has been repeatedly documented. Vitamin D deficiency is common among lupus patients. Vitamin D is recognized as a regulator of immune response. This study will explore the impact of vitamin D3 supplementation on IFN alpha expression in SLE patients. The study will last approximately 12 weeks and consist of three treatment groups: 1.) Participants will receive vitamin D3 2000 IU daily 2.) Participants will receive vitamin D3 4000 IU daily 3.) Participants will receive a vitamin D3 placebo daily. There will be four study visits for each participant. Visits will occur at screening, study entry, and Weeks 6 and 12. Physical examination, vital signs, and blood and urine tests will occur at all visits. For females of childbearing potential, a pregnancy test will be performed at screening and Week 6.
Interventions
DRUGVitamin D3
8% vitamin D3 powder, 84% microcrystalline cellulose, 8% fumed silica by weight
86% microcrystalline cellulose, 14% fumed silica by weight
Sponsors
Autoimmunity Centers of Excellence
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of SLE by American College of Rheumatology (ACR) criteria * Serum 25-OH vitamin D level of 20 ng/mL or less * Stable disease at screening, defined as a modified Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) of 4 or less * Interferon (IFN) signature present. More information about this criterion can be found in the protocol * Positive anti-double-stranded (anti-ds) DNA antibody blood test at screening * If on corticosteroids, the dose must be less than 20 mg per day and stable for 4 weeks prior to screening and at study entry * If on immunosuppressive or immunomodulatory medication such as azathioprine, methotrexate, leflunomide, mycophenolate, or hydroxychloroquine, the dose must be stable for 3 months prior to screening and at study entry * If receiving a multivitamin or a vitamin D supplement, the dose of vitamin D must be 800 IU daily or less and stable for the 3 months prior to screening and at study entry * Agree to use effective contraceptive methods for the duration of the study
Exclusion criteria
* Unwilling to stop using drugs or substances that may interfere with fat absorption * Hypercalcemia * Hypercalciuria * History of hyperparathyroidism * History of kidney stones * History of cancer, except cervical carcinoma in situ and resected basal and squamous cell carcinomas of the skin * Known history of chronic viral infections, including human immunodeficiency virus (HIV), Hepatitis B, and Hepatitis C * Known active tuberculosis * Any British Isles Lupus Assessment Group (BILAG) A or B manifestation with the exception of a BILAG B mucocutaneous manifestation * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver function tests greater than or equal to two times the upper limit of normal * Dialysis or serum creatinine greater than 1.5 mg/dL * Expectation by the investigator to increase corticosteroid or immunosuppressive or immunomodulatory medication dose at screening, study entry, or over the course of the study * Treatment with cyclophosphamide within 3 months of screening * Treatment with rituximab within 12 months of screening * Other investigational drug and or treatment during the 4 weeks or seven half lives of the other investigational drug prior to study entry * Drug or alcohol abuse within 6 months prior to study entry * Treatment with digoxin * Treatment with teriparatide * Any condition that, in the opinion of the investigator, would jeopardize the subject's safety following exposure to the study drug * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With an IFN Alpha Signature Response at Week 12 | 0, Week 12 | Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With IFN Alpha Signature at Week 12 | 0, Week 12 | An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation. |
| Percent of Participants With IFN Alpha Signature at Week 6 | Week 6 | An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation. |
| qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12 | 0, Week 12 | The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. This gene encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa). |
| qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6 | 0, Week 6 | The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa). |
| qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12 | 0, Week 12 | The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa). |
| qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6 | 0, Week 6 | The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa). |
| qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12 | 0, Week 12 | The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa). |
| qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6 | 0, Week 6 | The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa). |
| Change in Serum C3 Level From Baseline to Week 12 | 0, Week 12 | C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 12 is represented as a positive value (and vice versa). |
| Change in Serum C3 Level From Baseline to Week 6 | 0, Week 6 | C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 6 is represented as a positive value (and vice versa). |
| Change in Serum C4 Level From Baseline to Week 12 | 0, Week 12 | C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 12 is represented as a positive value (and vice versa). |
| Change in Serum C4 Level From Baseline to Week 6 | 0, Week 6 | Outcome measure description: C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 6 is represented as a positive value (and vice versa). |
| Percent of Participants With an IFN Alpha Signature Response at Week 6 | 0, Week 6 | Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation. |
| Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | 0, Week 6 | Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated. |
| Change in SELENA-SLEDAI Total Score From Baseline to Week 12 | 0, Week 12 | The modified Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus (SLE) Disease Activity Index (SELENA-SLEDAI) score is a weighted scale score ranging from 0 to 105 based on the presence or absence of 24 manifestations of SLE. The SELENA-SLEDAI assesses disease activity for 10 days prior to and including the day of assessment. For this study, the SELENA-SLEDAI score was modified to include proteinuria defined by dipstick rather than 24 hour urine. Positive change in the SELENA-SLEDAI score indicate increased disease activity. |
| Cardiorespiratory BILAG Status at Week 12 | Week 12 | The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Cardiorespiratory-specific body system. |
| Constitutional BILAG Status at Week 12 | Week 12 | The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Constitutional-specific body system. |
| Gastrointestinal BILAG Status at Week 12 | Week 12 | The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Gastrointestinal-specific body system. |
| Hematological BILAG Status at Week 12 | Week 12 | The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Hematological-specific body system. |
| Mucocutaneous BILAG Status at Week 12 | Week 12 | The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Mucocutaneous-specific body system. |
| Musculoskeletal BILAG Status at Week 12 | Week 12 | Outcome measure description: The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Musculoskeletal-specific body system. |
| Neuropsychiatric BILAG Status at Week 12 | Week 12 | The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Neuropsychiatric-specific body system. |
| Ophthalmic BILAG Status at Week 12 | Week 12 | The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Ophthalmic-specific body system. |
| Renal BILAG Status at Week 12 | Week 12 | The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Renal-specific body system. |
| Percent of Participants With Adverse Events of Grade 3 or Above | From start of study treatment through Week 12 | Grades are based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0 over the duration of the study. Participants who experienced at least one grade 3 or higher adverse event (AE) are counted only once. The adverse events are treatment-emergent, which means that the AE occurred after taking the first dose of study drug. |
| Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | 0, Week 12 | Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily). | 19 |
| Vitamin D3 2000 IU Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily). | 17 |
| Vitamin D3 4000 IU Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily). | 18 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Subject misrandomized | 0 | 1 | 1 |
| Overall Study | Subject's Decision | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Vitamin D3 2000 IU | Vitamin D3 4000 IU | Total |
|---|---|---|---|---|
| Age, Continuous | 38.7 years STANDARD_DEVIATION 12.3 | 36.5 years STANDARD_DEVIATION 10.9 | 38.3 years STANDARD_DEVIATION 12.9 | 37.9 years STANDARD_DEVIATION 11.9 |
| Modified SELENA-SLEDAI Score | 2.9 score STANDARD_DEVIATION 1.2 | 2.7 score STANDARD_DEVIATION 1.2 | 2.6 score STANDARD_DEVIATION 1 | 2.7 score STANDARD_DEVIATION 1.1 |
| Number of American College of Rheumatology (ACR) Criteria met at Screening | 5.4 number of criteria met STANDARD_DEVIATION 1.3 | 5.5 number of criteria met STANDARD_DEVIATION 1.1 | 5.8 number of criteria met STANDARD_DEVIATION 1.3 | 5.6 number of criteria met STANDARD_DEVIATION 1.2 |
| Region of Enrollment United States | 19 participants | 17 participants | 18 participants | 54 participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 16 Participants | 51 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Years with Systemic Lupus Erythematosus (SLE) at Baseline | 10.9 years STANDARD_DEVIATION 7.8 | 10.0 years STANDARD_DEVIATION 7.8 | 8.7 years STANDARD_DEVIATION 6 | 9.9 years STANDARD_DEVIATION 7.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 19 | 16 / 17 | 15 / 18 |
| serious Total, serious adverse events | 0 / 19 | 0 / 17 | 3 / 18 |
Outcome results
Primary
Percent of Participants With an IFN Alpha Signature Response at Week 12
Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.
Time frame: 0, Week 12
Population: Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU ) who did not have a signature were included in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With an IFN Alpha Signature Response at Week 12 | 36.8 Percent of participants |
| Vitamin D3 2000 IU | Percent of Participants With an IFN Alpha Signature Response at Week 12 | 23.5 Percent of participants |
| Vitamin D3 4000 IU | Percent of Participants With an IFN Alpha Signature Response at Week 12 | 27.8 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Percent of Participants With an IFN Alpha Signature Response at Week 12 | 25.7 Percent of participants |
p-value: 0.53Fisher Exact
Secondary
Cardiorespiratory BILAG Status at Week 12
The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Cardiorespiratory-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Cardiorespiratory BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 IU | Cardiorespiratory BILAG Status at Week 12 | 6.3 Percent with grade A or B |
| Vitamin D3 4000 IU | Cardiorespiratory BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Cardiorespiratory BILAG Status at Week 12 | 2.9 Percent with grade A or B |
p-value: 1Fisher Exact
Secondary
Change in SELENA-SLEDAI Total Score From Baseline to Week 12
The modified Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus (SLE) Disease Activity Index (SELENA-SLEDAI) score is a weighted scale score ranging from 0 to 105 based on the presence or absence of 24 manifestations of SLE. The SELENA-SLEDAI assesses disease activity for 10 days prior to and including the day of assessment. For this study, the SELENA-SLEDAI score was modified to include proteinuria defined by dipstick rather than 24 hour urine. Positive change in the SELENA-SLEDAI score indicate increased disease activity.
Time frame: 0, Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in SELENA-SLEDAI Total Score From Baseline to Week 12 | 0.0 Change in Scores on a Scale | Standard Deviation 0.7 |
| Vitamin D3 2000 IU | Change in SELENA-SLEDAI Total Score From Baseline to Week 12 | 0.2 Change in Scores on a Scale | Standard Deviation 1.8 |
| Vitamin D3 4000 IU | Change in SELENA-SLEDAI Total Score From Baseline to Week 12 | 0.2 Change in Scores on a Scale | Standard Deviation 1.9 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in SELENA-SLEDAI Total Score From Baseline to Week 12 | 0.2 Change in Scores on a Scale | Standard Deviation 1.8 |
p-value: 0.62F-tests derived from the GLM
Secondary
Change in Serum C3 Level From Baseline to Week 12
C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 12 is represented as a positive value (and vice versa).
Time frame: 0, Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Serum C3 Level From Baseline to Week 12 | 1.8 mg/dL | Standard Deviation 16.1 |
| Vitamin D3 2000 IU | Change in Serum C3 Level From Baseline to Week 12 | 0.7 mg/dL | Standard Deviation 11.1 |
| Vitamin D3 4000 IU | Change in Serum C3 Level From Baseline to Week 12 | 2.9 mg/dL | Standard Deviation 11.1 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Serum C3 Level From Baseline to Week 12 | 1.9 mg/dL | Standard Deviation 11 |
p-value: 0.96F-tests derived from the GLM
Secondary
Change in Serum C3 Level From Baseline to Week 6
C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 6 is represented as a positive value (and vice versa).
Time frame: 0, Week 6
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Serum C3 Level From Baseline to Week 6 | 3.3 mg/dL | Standard Deviation 10.9 |
| Vitamin D3 2000 IU | Change in Serum C3 Level From Baseline to Week 6 | 3.8 mg/dL | Standard Deviation 11.2 |
| Vitamin D3 4000 IU | Change in Serum C3 Level From Baseline to Week 6 | 3.7 mg/dL | Standard Deviation 10.3 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Serum C3 Level From Baseline to Week 6 | 3.8 mg/dL | Standard Deviation 10.5 |
p-value: 0.67F-tests derived from the GLM
Secondary
Change in Serum C4 Level From Baseline to Week 12
C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 12 is represented as a positive value (and vice versa).
Time frame: 0, Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Serum C4 Level From Baseline to Week 12 | 0.2 mg/dL | Standard Deviation 2.5 |
| Vitamin D3 2000 IU | Change in Serum C4 Level From Baseline to Week 12 | -0.3 mg/dL | Standard Deviation 2.9 |
| Vitamin D3 4000 IU | Change in Serum C4 Level From Baseline to Week 12 | 1.9 mg/dL | Standard Deviation 4.4 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Serum C4 Level From Baseline to Week 12 | .9 mg/dL | Standard Deviation 3.9 |
p-value: 0.59F-tests derived from the GLM
Secondary
Change in Serum C4 Level From Baseline to Week 6
Outcome measure description: C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 6 is represented as a positive value (and vice versa).
Time frame: 0, Week 6
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Serum C4 Level From Baseline to Week 6 | 0.3 mg/dL | Standard Deviation 3.3 |
| Vitamin D3 2000 IU | Change in Serum C4 Level From Baseline to Week 6 | -0.8 mg/dL | Standard Deviation 2.7 |
| Vitamin D3 4000 IU | Change in Serum C4 Level From Baseline to Week 6 | 0.4 mg/dL | Standard Deviation 2.8 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Serum C4 Level From Baseline to Week 6 | -0.2 mg/dL | Standard Deviation 2.7 |
p-value: 0.65F-tests derived from the GLM
Secondary
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12
Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.
Time frame: 0, Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Positive at Baseline, Positive at Week 12 | 94.1 Percent of participants |
| Placebo | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Positive at Baseline, Negative at Week 12 | 0.0 Percent of participants |
| Placebo | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Negative at Baseline, Negative at Week 12 | 5.9 Percent of participants |
| Placebo | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Negative at Baseline, Positive at Week 12 | 0.0 Percent of participants |
| Vitamin D3 2000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Positive at Baseline, Negative at Week 12 | 0.0 Percent of participants |
| Vitamin D3 2000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Negative at Baseline, Negative at Week 12 | 0.0 Percent of participants |
| Vitamin D3 2000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Positive at Baseline, Positive at Week 12 | 100.0 Percent of participants |
| Vitamin D3 2000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Negative at Baseline, Positive at Week 12 | 0.0 Percent of participants |
| Vitamin D3 4000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Negative at Baseline, Positive at Week 12 | 5.6 Percent of participants |
| Vitamin D3 4000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Positive at Baseline, Positive at Week 12 | 77.8 Percent of participants |
| Vitamin D3 4000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Negative at Baseline, Negative at Week 12 | 5.6 Percent of participants |
| Vitamin D3 4000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Positive at Baseline, Negative at Week 12 | 11.0 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Negative at Baseline, Negative at Week 12 | 2.9 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Positive at Baseline, Positive at Week 12 | 88.2 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Positive at Baseline, Negative at Week 12 | 6.0 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 | Negative at Baseline, Positive at Week 12 | 2.9 Percent of participants |
p-value: 0.86Fisher Exact
Secondary
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6
Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.
Time frame: 0, Week 6
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Positive at Baseline, Positive at Week 6 | 94.7 Percent of participants |
| Placebo | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Positive at Baseline, Negative at Week 6 | 0.0 Percent of participants |
| Placebo | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Negative at Baseline, Positive at Week 6 | 0.0 Percent of participants |
| Placebo | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Negative at Baseline, Negative at Week 6 | 5.3 Percent of participants |
| Vitamin D3 2000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Negative at Baseline, Negative at Week 6 | 0.0 Percent of participants |
| Vitamin D3 2000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Negative at Baseline, Positive at Week 6 | 0.0 Percent of participants |
| Vitamin D3 2000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Positive at Baseline, Negative at Week 6 | 6.3 Percent of participants |
| Vitamin D3 2000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Positive at Baseline, Positive at Week 6 | 93.7 Percent of participants |
| Vitamin D3 4000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Negative at Baseline, Positive at Week 6 | 0.0 Percent of participants |
| Vitamin D3 4000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Negative at Baseline, Negative at Week 6 | 11.1 Percent of participants |
| Vitamin D3 4000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Positive at Baseline, Negative at Week 6 | 0.0 Percent of participants |
| Vitamin D3 4000 IU | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Positive at Baseline, Positive at Week 6 | 88.9 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Negative at Baseline, Negative at Week 6 | 5.9 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Positive at Baseline, Positive at Week 6 | 91.2 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Positive at Baseline, Negative at Week 6 | 2.9 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 | Negative at Baseline, Positive at Week 6 | 0.0 Percent of participants |
p-value: 1Fisher Exact
Secondary
Constitutional BILAG Status at Week 12
The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Constitutional-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Constitutional BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 IU | Constitutional BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 4000 IU | Constitutional BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Constitutional BILAG Status at Week 12 | 0.0 Percent with grade A or B |
p-value: 1Fisher Exact
Secondary
Gastrointestinal BILAG Status at Week 12
The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Gastrointestinal-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Gastrointestinal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 IU | Gastrointestinal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 4000 IU | Gastrointestinal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Gastrointestinal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
p-value: 1Fisher Exact
Secondary
Hematological BILAG Status at Week 12
The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Hematological-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Hematological BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 IU | Hematological BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 4000 IU | Hematological BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Hematological BILAG Status at Week 12 | 0.0 Percent with grade A or B |
p-value: 1Fisher Exact
Secondary
Mucocutaneous BILAG Status at Week 12
The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Mucocutaneous-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Mucocutaneous BILAG Status at Week 12 | 5.6 Percent with grade A or B |
| Vitamin D3 2000 IU | Mucocutaneous BILAG Status at Week 12 | 12.5 Percent with grade A or B |
| Vitamin D3 4000 IU | Mucocutaneous BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Mucocutaneous BILAG Status at Week 12 | 5.9 Percent with grade A or B |
p-value: 1Fisher Exact
Secondary
Musculoskeletal BILAG Status at Week 12
Outcome measure description: The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Musculoskeletal-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Musculoskeletal BILAG Status at Week 12 | 5.6 Percent with grade A or B |
| Vitamin D3 2000 IU | Musculoskeletal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 4000 IU | Musculoskeletal BILAG Status at Week 12 | 11.1 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Musculoskeletal BILAG Status at Week 12 | 5.9 Percent with grade A or B |
p-value: 1Fisher Exact
Secondary
Neuropsychiatric BILAG Status at Week 12
The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Neuropsychiatric-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Neuropsychiatric BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 IU | Neuropsychiatric BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 4000 IU | Neuropsychiatric BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Neuropsychiatric BILAG Status at Week 12 | 0.0 Percent with grade A or B |
p-value: 1Fisher Exact
Secondary
Ophthalmic BILAG Status at Week 12
The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Ophthalmic-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Ophthalmic BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 IU | Ophthalmic BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 4000 IU | Ophthalmic BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Ophthalmic BILAG Status at Week 12 | 0.0 Percent with grade A or B |
p-value: 1Fisher Exact
Secondary
Percent of Participants With Adverse Events of Grade 3 or Above
Grades are based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0 over the duration of the study. Participants who experienced at least one grade 3 or higher adverse event (AE) are counted only once. The adverse events are treatment-emergent, which means that the AE occurred after taking the first dose of study drug.
Time frame: From start of study treatment through Week 12
Population: Safety
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With Adverse Events of Grade 3 or Above | 5.3 Percent of participants |
| Vitamin D3 2000 IU | Percent of Participants With Adverse Events of Grade 3 or Above | 23.5 Percent of participants |
| Vitamin D3 4000 IU | Percent of Participants With Adverse Events of Grade 3 or Above | 22.2 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Percent of Participants With Adverse Events of Grade 3 or Above | 22.9 Percent of participants |
p-value: 0.1Cochran-Mantel-Haenszel
Secondary
Percent of Participants With an IFN Alpha Signature Response at Week 6
Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.
Time frame: 0, Week 6
Population: Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU ) who did not have a signature were included in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With an IFN Alpha Signature Response at Week 6 | 36.8 Percent of participants |
| Vitamin D3 2000 IU | Percent of Participants With an IFN Alpha Signature Response at Week 6 | 17.6 Percent of participants |
| Vitamin D3 4000 IU | Percent of Participants With an IFN Alpha Signature Response at Week 6 | 5.6 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Percent of Participants With an IFN Alpha Signature Response at Week 6 | 11.4 Percent of participants |
p-value: 0.038Fisher Exact
Secondary
Percent of Participants With IFN Alpha Signature at Week 12
An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.
Time frame: 0, Week 12
Population: Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU) who did not have a signature were included in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With IFN Alpha Signature at Week 12 | 78.9 Percent of participants |
| Vitamin D3 2000 IU | Percent of Participants With IFN Alpha Signature at Week 12 | 94.1 Percent of participants |
| Vitamin D3 4000 IU | Percent of Participants With IFN Alpha Signature at Week 12 | 100.0 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Percent of Participants With IFN Alpha Signature at Week 12 | 97.1 Percent of participants |
p-value: 0.047Fisher Exact
Secondary
Percent of Participants With IFN Alpha Signature at Week 6
An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.
Time frame: Week 6
Population: Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU) who did not have a signature were included in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With IFN Alpha Signature at Week 6 | 84.2 Percent of participants |
| Vitamin D3 2000 IU | Percent of Participants With IFN Alpha Signature at Week 6 | 94.1 Percent of participants |
| Vitamin D3 4000 IU | Percent of Participants With IFN Alpha Signature at Week 6 | 100.0 Percent of participants |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Percent of Participants With IFN Alpha Signature at Week 6 | 97.1 Percent of participants |
p-value: 0.12Fisher Exact
Secondary
qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12
The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).
Time frame: 0, Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12 | -2.5 qRT-PCR fold change | Standard Deviation 16.4 |
| Vitamin D3 2000 IU | qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12 | -0.3 qRT-PCR fold change | Standard Deviation 9.8 |
| Vitamin D3 4000 IU | qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12 | 2.9 qRT-PCR fold change | Standard Deviation 11.7 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12 | 1.4 qRT-PCR fold change | Standard Deviation 10.8 |
p-value: 0.28F-tests derived from the GLM
Secondary
qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6
The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).
Time frame: 0, Week 6
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6 | -3.9 qRT-PCR fold change | Standard Deviation 12.8 |
| Vitamin D3 2000 IU | qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6 | -4.6 qRT-PCR fold change | Standard Deviation 11 |
| Vitamin D3 4000 IU | qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6 | 4.1 qRT-PCR fold change | Standard Deviation 5.9 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6 | 0.3 qRT-PCR fold change | Standard Deviation 9.4 |
p-value: 0.05F-tests derived from the GLM
Secondary
qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12
The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. This gene encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).
Time frame: 0, Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12 | -8.6 qRT-PCR fold change | Standard Deviation 40.5 |
| Vitamin D3 2000 IU | qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12 | -2.9 qRT-PCR fold change | Standard Deviation 57 |
| Vitamin D3 4000 IU | qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12 | 5.2 qRT-PCR fold change | Standard Deviation 33.9 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12 | 1.5 qRT-PCR fold change | Standard Deviation 45.3 |
p-value: 0.31F-tests derived from the GLM
Secondary
qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6
The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).
Time frame: 0, Week 6
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6 | -15.5 qRT-PCR fold change | Standard Deviation 38 |
| Vitamin D3 2000 IU | qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6 | -11.6 qRT-PCR fold change | Standard Deviation 35.5 |
| Vitamin D3 4000 IU | qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6 | 6.3 qRT-PCR fold change | Standard Deviation 18.1 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6 | -1.4 qRT-PCR fold change | Standard Deviation 28 |
p-value: 0.019F-tests derived from the GLM
Secondary
qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12
The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).
Time frame: 0, Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12 | -1.6 qRT-PCR fold change | Standard Deviation 14 |
| Vitamin D3 2000 IU | qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12 | 2.0 qRT-PCR fold change | Standard Deviation 12.5 |
| Vitamin D3 4000 IU | qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12 | 4.8 qRT-PCR fold change | Standard Deviation 11.6 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12 | 3.5 qRT-PCR fold change | Standard Deviation 11.9 |
p-value: 0.29F-tests derived from the GLM
Secondary
qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6
The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as fold change relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).
Time frame: 0, Week 6
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6 | -4.8 qRT-PCR fold change | Standard Deviation 10.5 |
| Vitamin D3 2000 IU | qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6 | 1.4 qRT-PCR fold change | Standard Deviation 19.5 |
| Vitamin D3 4000 IU | qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6 | 0.7 qRT-PCR fold change | Standard Deviation 6.7 |
| Vitamin D3 2000 and 4000 IU (Pooled ) | qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6 | 1.0 qRT-PCR fold change | Standard Deviation 13.5 |
p-value: 0.014F-tests derived from the GLM
Secondary
Renal BILAG Status at Week 12
The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the Renal-specific body system.
Time frame: Week 12
Population: Modified Intent-to-Treat with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Renal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 IU | Renal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 4000 IU | Renal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
| Vitamin D3 2000 and 4000 IU (Pooled ) | Renal BILAG Status at Week 12 | 0.0 Percent with grade A or B |
p-value: 1Fisher Exact