Systemic Lupus Erythematosus
Conditions
Keywords
MEDI-546, Anifrolumab, Systemic Lupus Erythematosus
Brief summary
The purpose of this study is to evaluate the efficacy and safety of MEDI-546 compared to placebo in subjects with chronic, moderately-to-severely active systemic lupus erythematosus (SLE) with an inadequate response to standard of care treatment for SLE.
Detailed description
This is a Phase 2, multinational, multicenter, randomized, double-blind, placebo controlled, parallel-group study to evaluate the efficacy and safety of 2 intravenous (IV) treatment regimens in adult participants with chronic, moderately-to-severely active SLE with an inadequate response to SOC SLE. The investigational product (anifrolumab or placebo) will be administered as a fixed dose every 4 weeks (28 days) for a total of 13 doses.
Interventions
BIOLOGICALAnifrolumab 300 mg
Participants will receive 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
BIOLOGICALAnifrolumab 1000 mg
Participants will receive 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
OTHERPlacebo
Participants will receive placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Fulfills at least 4 of the 11 American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) including a positive antinuclear antibody (ANA) greater than or equal to 1:80 or elevated anti-double-stranded DNA or anti-Smith antibody at screening * Pediatric or adult SLE with chronic disease activity for greater than or equal to 24 weeks * Weight greater than or equal to 40 kg * Currently receiving stable dose of oral prednisone (or equivalent) less than or equal to 40 mg/day and/or antimalarials/immunosuppressives * Active moderate to severe SLE disease based on SLE disease activity score (SLEDAI) and British Isles Lupus Assessment Group Index (BILAG) and Physicians Global Assessment * No evidence of cervical malignancy on Pap smear within 2 years of randomization * Female participants must be willing to avoid pregnancy * Negative tuberculosis (TB) test or newly positive TB test due to latent TB for which treatment must be initiated at or before randomization.
Exclusion criteria
* Active severe SLE-driven renal disease or unstable renal disease prior to screening * Active severe or unstable neuropsychiatric SLE * Clinically significant active infection including ongoing and chronic infections * History of human immunodeficiency virus (HIV) * Confirmed Positive tests for hepatitis B or positive test for hepatitis C * History of severe herpes infection such as herpes encephalitis, ophthalmic herpes, disseminated herpes * Live or attenuated vaccine within 4 weeks prior to screening * Participants with significant hematologic abnormalities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169 | Day 169 | An SRI (4) responder defined as a participant who had 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of greater than or equal to (\>=) 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index 'A' organ system score and no more than one new or worsening BILAG-2004 Index 'B' organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\]. SRI was analyzed by a logistic regression model. |
| Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169 | Day 169 | Type I IFN signature in whole blood assessed by using a 4-gene diagnostic test. The blood samples collected were to be used to prospectively identify participants as IFN test-high or test-low. The results of this test were used to stratify participants. An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of \>= 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 \[less than 10 mg/day and less or equal to the dose received on Day 1\]. SRI was analyzed by a logistic regression model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 1 (Baseline) to Day 422 (End of Study) | An adverse event (AE) was any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A serious AE (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly (in offspring of participant). AEs may be treatment emergent (TE) \[that is, occurring after initial receipt of investigational product\] or non-TE. An AESI is one of scientific and medical concern specific to understanding biologics and requires close monitoring and rapid communication by investigator to sponsor. |
| Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Day 1 (Baseline) to Day 422 (End of Study) | Any medically significant change in laboratory evaluations were recorded as Treatment emergent adverse events. |
| Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Day 1 (Baseline) to Day 422 (End of Study) | Vital sign parameters are temperature, blood pressure, respiratory rate, heart rate and weight. Vital signs abnormalities were reported as TEAEs. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Day 1 (Baseline) to Day 422 (End of Study) | Any medically significant changes from the screening ECG was recorded as TEAEs. An abnormal ECG findings such as QT prolonged were reported as treatment emergent adverse events. |
| Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Days 1, 85, 141, 169, 253, 337 (Treatment Phase), 365, 396, and 422 (Follow-up Period) | Anti-drug antibody responses to anifrolumab in serum were evaluated. |
| Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365 | Day 365 | An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of \>= 4 points; 2) no worsening of disease from baseline as measured by the MDGA (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 281 through Day 365 (less than 10 mg/day and less or equal to the dose received on Day 1). SRI was analyzed by a logistic regression model. |
| Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 | Pre-infusion and 15 minutes post-infusion on Day 1, 169 and 337 | Maximum plasma concentration (Cmax) was defined as the peak plasma level of anifrolumab, derived from plasma concentration -time data. |
| Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab | Pre-infusion and 15 minutes post-infusion on Day 169 and 337 | Accumulation ratio for maximum plasma concentration (Cmax,AR) of anifrolumab after multiple administration at Day 169 and 337 was calculated. |
| Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 | Pre-infusion and 15 minutes post-infusion on Day 29, 169 and 365 | Trough concentration (Ctrough) of anifrolumab at Day 29, 169 and 365 were calculated. |
| Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365 | Pre-infusion and 15 minutes post-infusion on Day 169 and 365 | Accumulation ratio for trough concentration (Ctrough,AR) of anifrolumab after multiple administration at Day 169 and 365 was calculated. |
| Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Days 29, 85, 141, 169, 253, 337 (treatment phase), on Days 365, 396, and 422 (follow up period) | The PD positive and negative gene signature was determined by comparing the expression of type I IFN-inducible genes in a 21-gene panel in study participants relative to pooled normal blood collected from healthy participants. |
| Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/Day of Prednisone or Equivalent at Baseline Who Were Able to Taper to Less Than or Equal to (<=) 7.5 mg/Day at Day 365 | Day 365 | Participants on OCS \>=10 mg/day of prednisone or equivalent at baseline who were able to taper to \<= 7.5 mg/day at Day 365 were evaluated. |
Countries
Brazil, Bulgaria, Colombia, Czechia, Hungary, India, Mexico, Peru, Poland, Romania, South Korea, Taiwan, Ukraine, United States
Participant flow
Pre-assignment details
A total of 626 participants were screened out of which 319 participants did not meet eligibility criteria and were considered screen failures, and 307 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks. | 103 |
| Anifrolumab 300 mg Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks. | 100 |
| Anifrolumab 1000 mg Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks. | 104 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | AE/SAEs | 2 | 1 | 1 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Did not complete all 3 follow-up visits | 2 | 5 | 2 |
| Overall Study | Inadequate venous access | 0 | 2 | 0 |
| Overall Study | Investigator decision | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 2 | 2 |
| Overall Study | Received prohibited medication | 1 | 0 | 0 |
| Overall Study | Sponsor decision | 4 | 1 | 4 |
| Overall Study | Subject choice/Subject moved | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 3 | 8 |
Baseline characteristics
| Characteristic | Total | Anifrolumab 1000 mg | Placebo | Anifrolumab 300 mg |
|---|---|---|---|---|
| Age, Continuous | 39.8 Years STANDARD_DEVIATION 12.2 | 40.8 Years STANDARD_DEVIATION 11.6 | 39.2 Years STANDARD_DEVIATION 12.9 | 39.3 Years STANDARD_DEVIATION 12 |
| Baseline weight | 69.48 kilogram STANDARD_DEVIATION 17.79 | 70.74 kilogram STANDARD_DEVIATION 17.29 | 68.08 kilogram STANDARD_DEVIATION 18.98 | 69.62 kilogram STANDARD_DEVIATION 17.09 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 5 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 22 Participants | 6 Participants | 13 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 41 Participants | 10 Participants | 12 Participants | 19 Participants |
| Race/Ethnicity, Customized Multiple category checked | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 109 Participants | 36 Participants | 36 Participants | 37 Participants |
| Race/Ethnicity, Customized White | 128 Participants | 51 Participants | 41 Participants | 36 Participants |
| Region of Enrollment BRAZIL | 3 Participants | 0 Participants | 3 Participants | 0 Participants |
| Region of Enrollment BULGARIA | 9 Participants | 4 Participants | 3 Participants | 2 Participants |
| Region of Enrollment COLOMBIA | 44 Participants | 18 Participants | 16 Participants | 10 Participants |
| Region of Enrollment CZECH REPUBLIC | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Region of Enrollment HUNGARY | 10 Participants | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment INDIA | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Region of Enrollment MEXICO | 16 Participants | 5 Participants | 4 Participants | 7 Participants |
| Region of Enrollment PERU | 50 Participants | 13 Participants | 15 Participants | 22 Participants |
| Region of Enrollment POLAND | 32 Participants | 12 Participants | 11 Participants | 9 Participants |
| Region of Enrollment ROMANIA | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment SOUTH KOREA | 6 Participants | 3 Participants | 3 Participants | 0 Participants |
| Region of Enrollment TAIWAN | 12 Participants | 3 Participants | 7 Participants | 2 Participants |
| Region of Enrollment UKRAINE | 22 Participants | 11 Participants | 7 Participants | 4 Participants |
| Region of Enrollment UNITED STATES OF AMERICA | 95 Participants | 29 Participants | 28 Participants | 38 Participants |
| Sex: Female, Male Female | 287 Participants | 99 Participants | 94 Participants | 94 Participants |
| Sex: Female, Male Male | 20 Participants | 5 Participants | 9 Participants | 6 Participants |
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 | 36 / 101 | 40 / 99 | 46 / 105 |
| serious Total, serious adverse events | 19 / 101 | 16 / 99 | 18 / 105 |
Outcome results
Primary
Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169
An SRI (4) responder defined as a participant who had 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of greater than or equal to (\>=) 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index 'A' organ system score and no more than one new or worsening BILAG-2004 Index 'B' organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\]. SRI was analyzed by a logistic regression model.
Time frame: Day 169
Population: The modified Intent-To-Treat (mITT) population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, N signifies evaluable participants for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169 | 17.6 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169 | 34.3 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169 | 28.8 Percentage of Participants |
Comparison: All-comersp-value: 0.01490% CI: [1.33, 4.26]Regression, Logistic
Comparison: All-comersp-value: 0.06390% CI: [1.08, 3.49]Regression, Logistic
Primary
Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169
Type I IFN signature in whole blood assessed by using a 4-gene diagnostic test. The blood samples collected were to be used to prospectively identify participants as IFN test-high or test-low. The results of this test were used to stratify participants. An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of \>= 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 \[less than 10 mg/day and less or equal to the dose received on Day 1\]. SRI was analyzed by a logistic regression model.
Time frame: Day 169
Population: The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, N signifies evaluable participants for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169 | 13.2 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169 | 36 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169 | 28.2 Percentage of Participants |
Comparison: Highp-value: 0.00490% CI: [1.72, 7.32]Regression, Logistic
Comparison: Highp-value: 0.02990% CI: [1.27, 5.53]Regression, Logistic
Secondary
Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab
Accumulation ratio for maximum plasma concentration (Cmax,AR) of anifrolumab after multiple administration at Day 169 and 337 was calculated.
Time frame: Pre-infusion and 15 minutes post-infusion on Day 169 and 337
Population: The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, N signifies evaluable participants for this outcome measure and n signifies evaluable participants for the specified category of the arms respectively.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab | Day 169 (n=81,86) | 1.36 Ratio | Full Range 63.7 |
| Placebo | Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab | Day 337 (n=78,66) | 1.56 Ratio | Full Range 64.6 |
| Anifrolumab 300 mg | Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab | Day 169 (n=81,86) | 1.43 Ratio | Full Range 137 |
| Anifrolumab 300 mg | Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab | Day 337 (n=78,66) | 1.76 Ratio | Full Range 140 |
Secondary
Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365
Accumulation ratio for trough concentration (Ctrough,AR) of anifrolumab after multiple administration at Day 169 and 365 was calculated.
Time frame: Pre-infusion and 15 minutes post-infusion on Day 169 and 365
Population: The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, N signifies evaluable participants for this outcome measure and n signifies evaluable participants for the specified category of the arms respectively.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365 | Day 169 (n=82,86) | 2.49 Ratio | Full Range 63.7 |
| Placebo | Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365 | Day 365 (n=79,70) | 3.06 Ratio | Full Range 64.6 |
| Anifrolumab 300 mg | Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365 | Day 169 (n=82,86) | 2.29 Ratio | Full Range 137 |
| Anifrolumab 300 mg | Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365 | Day 365 (n=79,70) | 3.02 Ratio | Full Range 140 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337
Maximum plasma concentration (Cmax) was defined as the peak plasma level of anifrolumab, derived from plasma concentration -time data.
Time frame: Pre-infusion and 15 minutes post-infusion on Day 1, 169 and 337
Population: The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, N signifies evaluable participants for this outcome measure and n signifies evaluable participants for the specified category of the arms respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 | Day 1 (n=98,104) | 82.8 micrograms/milliliter (mcg/mL) | Standard Deviation 64.5 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 | Day 169 (n=86,87) | 110 micrograms/milliliter (mcg/mL) | Standard Deviation 63.7 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 | Day 337 (n=83,67) | 127 micrograms/milliliter (mcg/mL) | Standard Deviation 64.6 |
| Anifrolumab 300 mg | Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 | Day 1 (n=98,104) | 248 micrograms/milliliter (mcg/mL) | Standard Deviation 79.9 |
| Anifrolumab 300 mg | Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 | Day 169 (n=86,87) | 375 micrograms/milliliter (mcg/mL) | Standard Deviation 137 |
| Anifrolumab 300 mg | Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 | Day 337 (n=83,67) | 439 micrograms/milliliter (mcg/mL) | Standard Deviation 140 |
Secondary
Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature
The PD positive and negative gene signature was determined by comparing the expression of type I IFN-inducible genes in a 21-gene panel in study participants relative to pooled normal blood collected from healthy participants.
Time frame: Days 29, 85, 141, 169, 253, 337 (treatment phase), on Days 365, 396, and 422 (follow up period)
Population: The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, N signifies evaluable participants for this outcome measure and n signifies evaluable participants for the specified category of the arms respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 169 (n= 56, 60, 66) | -17.122 Ratio | Standard Deviation 67.603 |
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 422 (n= 53, 57, 55) | -31.777 Ratio | Standard Deviation 70.173 |
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 337 (n= 49, 59, 53) | -13.784 Ratio | Standard Deviation 45.541 |
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 253 (n= 50, 60, 61) | -9.908 Ratio | Standard Deviation 49.826 |
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 29 (n= 68, 66, 73) | -0.753 Ratio | Standard Deviation 44.678 |
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 396 (n= 56, 61, 64) | -22.106 Ratio | Standard Deviation 64.529 |
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 141 (n= 59, 64, 68) | -25.411 Ratio | Standard Deviation 78.391 |
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 85 (n= 63, 62, 72) | -5.412 Ratio | Standard Deviation 44.354 |
| Placebo | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 365 (n= 58, 66, 68) | -6.428 Ratio | Standard Deviation 50.358 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 253 (n= 50, 60, 61) | 73.972 Ratio | Standard Deviation 41.267 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 29 (n= 68, 66, 73) | 70.194 Ratio | Standard Deviation 40.028 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 85 (n= 63, 62, 72) | 72.639 Ratio | Standard Deviation 34.443 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 141 (n= 59, 64, 68) | 73.662 Ratio | Standard Deviation 36.684 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 169 (n= 56, 60, 66) | 77.364 Ratio | Standard Deviation 30.733 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 337 (n= 49, 59, 53) | 79.363 Ratio | Standard Deviation 28.803 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 365 (n= 58, 66, 68) | 72.796 Ratio | Standard Deviation 35.552 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 396 (n= 56, 61, 64) | 11.510 Ratio | Standard Deviation 56.385 |
| Anifrolumab 300 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 422 (n= 53, 57, 55) | -0.836 Ratio | Standard Deviation 44.596 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 141 (n= 59, 64, 68) | 88.569 Ratio | Standard Deviation 10.364 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 29 (n= 68, 66, 73) | 82.056 Ratio | Standard Deviation 16.108 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 365 (n= 58, 66, 68) | 81.115 Ratio | Standard Deviation 53.121 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 85 (n= 63, 62, 72) | 79.350 Ratio | Standard Deviation 40.428 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 422 (n= 53, 57, 55) | 37.532 Ratio | Standard Deviation 66.339 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 253 (n= 50, 60, 61) | 86.099 Ratio | Standard Deviation 15.615 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 169 (n= 56, 60, 66) | 88.126 Ratio | Standard Deviation 10.278 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 396 (n= 56, 61, 64) | 72.291 Ratio | Standard Deviation 31.182 |
| Anifrolumab 1000 mg | Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature | Day 337 (n= 49, 59, 53) | 87.811 Ratio | Standard Deviation 8.41 |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events
Any medically significant change in laboratory evaluations were recorded as Treatment emergent adverse events.
Time frame: Day 1 (Baseline) to Day 422 (End of Study)
Population: The safety population included participants who received any investigational product. Here, N signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Thrombocytosis | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Leukocytosis | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Leukopenia | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Neutropenia | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Anaemia | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Iron deficiency anaemia | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Lymphopenia | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Microcytic anaemia | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Neutrophil count increased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | White blood cell count increased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Monocyte count increased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypochromic anaemia | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyperglycaemia | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hepatic enzyme increased | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypocalcaemia | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Lipid metabolism disorder | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood creatine phosphokinase increased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyperlipidaemia | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypertriglyceridaemia | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyponatraemia | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Gamma-glutamyltransferase increased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Glomerular filtration rate decreased | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Transaminases increased | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Dyslipidaemia | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase abnormal | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase abnormal | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood triglycerides abnormal | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Glomerular filtration rate increased | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypertriglyceridaemia | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Neutrophil count increased | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 3 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Lipid metabolism disorder | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Leukocytosis | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyperglycaemia | 3 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood triglycerides abnormal | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Leukopenia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyponatraemia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Neutropenia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Glomerular filtration rate increased | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Dyslipidaemia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Anaemia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 2 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hepatic enzyme increased | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Iron deficiency anaemia | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypochromic anaemia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Lymphopenia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood creatine phosphokinase increased | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Transaminases increased | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Microcytic anaemia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypocalcaemia | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase abnormal | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Thrombocytosis | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyperlipidaemia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Gamma-glutamyltransferase increased | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | White blood cell count increased | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Glomerular filtration rate decreased | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase abnormal | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Monocyte count increased | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Microcytic anaemia | 2 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase abnormal | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypochromic anaemia | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyperglycaemia | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Glomerular filtration rate decreased | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hepatic enzyme increased | 3 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypocalcaemia | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Transaminases increased | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Lipid metabolism disorder | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Dyslipidaemia | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood creatine phosphokinase increased | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood triglycerides abnormal | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyperlipidaemia | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Neutrophil count increased | 3 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hypertriglyceridaemia | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Leukocytosis | 2 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase abnormal | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Leukopenia | 3 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Neutropenia | 3 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Hyponatraemia | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Anaemia | 2 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Glomerular filtration rate increased | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Iron deficiency anaemia | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Lymphopenia | 2 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Monocyte count increased | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Thrombocytosis | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | White blood cell count increased | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events | Gamma-glutamyltransferase increased | 0 Participants |
Secondary
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Any medically significant changes from the screening ECG was recorded as TEAEs. An abnormal ECG findings such as QT prolonged were reported as treatment emergent adverse events.
Time frame: Day 1 (Baseline) to Day 422 (End of Study)
Population: The safety population included participants who received any investigational product. Here, N signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A serious AE (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly (in offspring of participant). AEs may be treatment emergent (TE) \[that is, occurring after initial receipt of investigational product\] or non-TE. An AESI is one of scientific and medical concern specific to understanding biologics and requires close monitoring and rapid communication by investigator to sponsor.
Time frame: Day 1 (Baseline) to Day 422 (End of Study)
Population: The safety population included participants who received any investigational product. Here, N signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 19 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 78 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AESIs | 12 Participants |
| Anifrolumab 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 16 Participants |
| Anifrolumab 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 84 Participants |
| Anifrolumab 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AESIs | 10 Participants |
| Anifrolumab 1000 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 90 Participants |
| Anifrolumab 1000 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AESIs | 15 Participants |
| Anifrolumab 1000 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 18 Participants |
Secondary
Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Vital sign parameters are temperature, blood pressure, respiratory rate, heart rate and weight. Vital signs abnormalities were reported as TEAEs.
Time frame: Day 1 (Baseline) to Day 422 (End of Study)
Population: The safety population included participants who received any investigational product. Here, N signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 7 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 5 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure increased | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure decreased | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Secondary hypertension | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure abnormal | 1 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Chills | 1 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypertensive emergency | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Chills | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 3 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Secondary hypertension | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 1 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypertensive emergency | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure abnormal | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure increased | 2 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 0 Participants |
| Anifrolumab 300 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure decreased | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure abnormal | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure decreased | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Secondary hypertension | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Chills | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 1 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 2 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hypertensive emergency | 0 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 3 Participants |
| Anifrolumab 1000 mg | Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Blood pressure increased | 1 Participants |
Secondary
Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365
An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of \>= 4 points; 2) no worsening of disease from baseline as measured by the MDGA (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 281 through Day 365 (less than 10 mg/day and less or equal to the dose received on Day 1). SRI was analyzed by a logistic regression model.
Time frame: Day 365
Population: The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, N signifies evaluable participants for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365 | 25.5 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365 | 51.5 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365 | 38.5 Percentage of Participants |
Secondary
Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/Day of Prednisone or Equivalent at Baseline Who Were Able to Taper to Less Than or Equal to (<=) 7.5 mg/Day at Day 365
Participants on OCS \>=10 mg/day of prednisone or equivalent at baseline who were able to taper to \<= 7.5 mg/day at Day 365 were evaluated.
Time frame: Day 365
Population: The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, N signifies evaluable participants for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/Day of Prednisone or Equivalent at Baseline Who Were Able to Taper to Less Than or Equal to (<=) 7.5 mg/Day at Day 365 | 26.6 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/Day of Prednisone or Equivalent at Baseline Who Were Able to Taper to Less Than or Equal to (<=) 7.5 mg/Day at Day 365 | 56.4 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/Day of Prednisone or Equivalent at Baseline Who Were Able to Taper to Less Than or Equal to (<=) 7.5 mg/Day at Day 365 | 31.7 Percentage of Participants |
Secondary
Percentage of SLE Participants With Positive Anti-drug Antibody (ADA)
Anti-drug antibody responses to anifrolumab in serum were evaluated.
Time frame: Days 1, 85, 141, 169, 253, 337 (Treatment Phase), 365, 396, and 422 (Follow-up Period)
Population: The safety population included participants who received any investigational product. Here, N and n signifies evaluable participants for this outcome measure and for specified category of the arms respectively. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in Anifrolumab 1000 mg group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 141 (n=84,94,93) | 2.4 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 396 (n=78,88,90) | 0.0 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 422 (n=76,86,77) | 1.3 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 1 (n=100,98,105) | 1.0 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Any Visit Post Baseline (n= 99,98,102) | 3.0 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 365 (n=85,96,94) | 0.0 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 169 (n=81,89,92) | 2.5 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 85 (n=91,93,98) | 1.1 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 253 (n=72,86,86) | 0.0 Percentage of Participants |
| Placebo | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 337 (n=70,87,76) | 0.0 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 365 (n=85,96,94) | 1.0 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 169 (n=81,89,92) | 0.0 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 396 (n=78,88,90) | 2.3 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 141 (n=84,94,93) | 0.0 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 337 (n=70,87,76) | 1.1 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 422 (n=76,86,77) | 5.8 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 1 (n=100,98,105) | 1.0 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 253 (n=72,86,86) | 1.2 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Any Visit Post Baseline (n= 99,98,102) | 5.1 Percentage of Participants |
| Anifrolumab 300 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 85 (n=91,93,98) | 0.0 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Any Visit Post Baseline (n= 99,98,102) | 2.0 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 1 (n=100,98,105) | 1.9 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 85 (n=91,93,98) | 0.0 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 141 (n=84,94,93) | 2.2 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 169 (n=81,89,92) | 1.1 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 253 (n=72,86,86) | 0.0 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 337 (n=70,87,76) | 0.0 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 365 (n=85,96,94) | 1.1 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 396 (n=78,88,90) | 0.0 Percentage of Participants |
| Anifrolumab 1000 mg | Percentage of SLE Participants With Positive Anti-drug Antibody (ADA) | Day 422 (n=76,86,77) | 0.0 Percentage of Participants |
Secondary
Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365
Trough concentration (Ctrough) of anifrolumab at Day 29, 169 and 365 were calculated.
Time frame: Pre-infusion and 15 minutes post-infusion on Day 29, 169 and 365
Population: The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, N signifies evaluable participants for this outcome measure and n signifies evaluable participants for the specified category of the arms respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 | Day 29 (n=95,99) | 7.95 microgram per milliliter | Standard Deviation 6.17 |
| Placebo | Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 | Day 169 (n=87,87) | 18.4 microgram per milliliter | Standard Deviation 12.9 |
| Placebo | Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 | Day 365 (n=83,71) | 23.6 microgram per milliliter | Standard Deviation 15.5 |
| Anifrolumab 300 mg | Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 | Day 29 (n=95,99) | 46.8 microgram per milliliter | Standard Deviation 24.6 |
| Anifrolumab 300 mg | Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 | Day 169 (n=87,87) | 110 microgram per milliliter | Standard Deviation 60.5 |
| Anifrolumab 300 mg | Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 | Day 365 (n=83,71) | 154 microgram per milliliter | Standard Deviation 89.2 |