Systemic Lupus Erythematosus
Conditions
Keywords
Sifalimumab, MEDI-545
Brief summary
The objective of this study is to assess the safety and tolerability of sifalimumab in adult participants with active systemic lupus erythematosus (SLE) or active dermatomyositis (DM) or polymyositis (PM) who participated in the following clinical studies: MI-CP151, MI-CP152, or MI-CP179.
Detailed description
The primary objective of this study is to evaluate the long-term safety and tolerability of multiple intravenous (IV) doses of sifalimumab in adult participants with active SLE or DM or PM who were previously treated with investigational product (sifalimumab or placebo) in one of the following sifalimumab clinical studies: MI-CP151, MI-CP152, or MI-CP179.
Interventions
DRUGSifalimumab
All participants will receive intravenous (IV) sifalimumab as fixed dose of 500 mg every 2 weeks (Q2W) on Day 1, Week 2, and Week 4, then every 4 weeks (Q4W) thereafter for a total of 156 weeks. The initial fixed dose of 500 mg is increased to 600 mg with subsequent protocol amendment.
Sponsors
PPD Development, LP
MedImmune LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older at the time of screening. * Written informed consent and any locally required authorization \[example, Health Insurance Portability and Accountability Act (HIPAA) in the United States of America (USA), European Union (EU) Data Privacy Directive in the EU\] obtained from the participant/legal representative prior to performing any protocol-related procedures, including Screening evaluations. * Female participants of childbearing potential who are sexually active must use must use 2 effective methods of avoiding pregnancy from Screening, and must agree to continue using such precautions for 26 weeks after the final dose of investigational product. * Males, unless surgically sterile, must use 2 effective methods of birth control with a female partner and must agree to continue using such contraceptive precautions from Screening until 26 weeks after the final dose of investigational product. If female, unless cervix has been surgically removed, have had a Pap smear with no evidence of malignancy within 6 months of baseline (defined as Day 1). * Must have qualified for and received investigational product (sifalimumab or placebo) and completed the treatment period plus follow-up (through Day 266 for participants from MI-CP151 and MI-CP152 or through Day 168 for participants from MI-CP179) in one of the following sifalimumab clinical studies: MI-CP151, MI-CP152, or MI-CP179, ability to complete the study period through the final visit, willing to forego other forms of experimental drug treatment during the study.
Exclusion criteria
* Discontinued investigational product (sifalimumab) for safety reasons from any previous sifalimumab clinical study. * For participants with systemic lupus erythematosus (SLE): Active severe or unstable neuropsychiatric SLE, that in the opinion of the investigator, would make the participant unsuitable for the study or unable to fully understand the informed consent, Active severe or unstable renal disease that in the opinion of the investigator would make the participant unsuitable for this study * For participants with dermatomyositis (DM) or polymyositis (PM): Inclusion body myositis, cancer-associated myositis, myositis associated with another connective tissue disease, environmentally-associated myositis, or drug-related myopathy, a history of or a family history of non-inflammatory myopathy, scapular winging, atrophy, or hypertrophy of the calf muscles, Active Hepatitis A, confirmed positive tests for hepatitis B surface antigen (HbsAg) and hepatitis B core antibody (HbcAb) or hepatitis C serology. Isolated HbcAb positivity will be explored with additional reflex testing to determine eligibility. * Evidence of active tuberculosis (TB), either treated or untreated, or latent TB without completion of an appropriate course of treatment or appropriate ongoing prophylactic treatment, history of severe viral infection, such as disseminated herpes, herpes encephalitis, or ophthalmic herpes. * Any of the following medications within 6 months before entry into the study: Leflunomide greater than (\>) 20 milligram/day, Cyclophosphamide (or any other alkylating agent). * Any of the following medications within 28 days before entry into the study: Prednisone or equivalent \> 30 mg/day or \> 0.5 mg/kg, whichever is the lesser amount, Cyclosporine at any dose, Thalidomide at any dose, Interferon alpha 2b, Hydroxychloroquine \> 600 mg/day, Mycophenolate mofetil \> 3 gram/day, Methotrexate \> 25 mg/week, Azathioprine \> 3 mg/kilogram (kg)/day, Combination of leflunomide and methotrexate * Nonstable doses of one or more of the following medications within 28 days before entry into the study: Hydroxychloroquine, Mycophenolate mofetil, Methotrexate, Azathioprine * At Screening blood tests (within 28 days before entry into the study), any of the following: Total bilirubin \> upper limit of normal (ULN), Neutrophil count \< 1,500/microliter (mcl) (or \< 1.5 × 109/L), Platelet count \< 60,000/microliter (mcl) (or \< 60 × 109/L), Hemoglobin (Hgb) \< 7 gram per decilitre (g/dL) (or \< 70 g/L).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | From start of study drug administration until week 182 | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received investigational product. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of investigational product and 30 days after the last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sifalimumab | Pre-infusion and End of Infusion on Day 1 | The Tmax is the time to reach maximum observed plasma concentration of sifalimumab. |
| Time to Last Quantifiable Plasma Concentration (Tlast) of Sifalimumab | Pre-infusion and End of Infusion on Day 1 | The Tlast is the time to last quantifiable plasma concentration (Tlast) of sifalimumab. |
| Minimum Observed Serum Concentration (Ctrough) of Sifalimumab | Pre-infusion and End of Infusion on Day 1 | The Ctrough is the minimum observed serum concentration of sifalimumab. |
| Maximum Observed Serum Concentration (Cmax) for Sifalimumab | Pre-infusion and End of Infusion on Day 1 | The Cmax is the maximum observed plasma concentration of sifalimumab. |
| Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Sifalimumab | Pre-infusion and End of Infusion on Day 1 and Week 2, 4, 8, 12, 24, 52, 104, 156 and 168 | The Ctrough is the minimum observed serum concentration at steady state of sifalimumab. |
| Accumulation Index for Minimum Observed Serum Concentration (Ctrough) of Sifalimumab | Pre-infusion and End of Infusion on Day 1 and Week 2, 4, 8, 12, 24, 52, 104, 156 and 168 | The Ctrough is the minimum observed serum concentration of sifalimumab. Accumulation Index is calculated as Ctrough value at steady state divided by Ctrough value after first dose. |
| Number of Participants With Positive Anti-Drug Antibody | Day 1 and Week 12, 24, 52, 104, 156 and 168 | Participants tested for immunogenicity to Sifalimumab (MEDI-545) from Day 1 to the end of study. |
| Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCtau) of Sifalimumab | Pre-infusion and End of Infusion on Day 1 | The AUCtau is the area under the serum concentration-time curve over the dosing interval of sifalimumab. |
Countries
Brazil, Canada, Chile, United States
Participant flow
Pre-assignment details
A total of 118 participants were Screened out of which 15 participants did not meet eligibility criteria and were considered screen failures, and 103 participants were entered into the study.
Participants by arm
| Arm | Count |
|---|---|
| MEDI-545 All participants received intravenous (IV) sifalimumab as fixed dose of 500 mg every 2 weeks (Q2W) on Day 1, Week 2, and Week 4, then every 4 weeks (Q4W) thereafter for a total of 156 weeks. The initial fixed dose of 500 mg was increased to 600 mg with subsequent protocol amendment. | 103 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Adverse Event of Diverticulitis | 1 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 6 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Patient Wanted to Pursue Other Treatment | 1 |
| Overall Study | Per Principal Investigator's Discretion | 1 |
| Overall Study | Serious Adverse Event | 1 |
| Overall Study | Unfavorable Risk-Benefit Analysis | 1 |
| Overall Study | Withdrawal by Subject | 22 |
Baseline characteristics
| Characteristic | MEDI-545 |
|---|---|
| Age, Continuous | 48.2 Years STANDARD_DEVIATION 9.9 |
| Age, Customized < 40 | 21 Participants |
| Age, Customized 40 - <65 | 78 Participants |
| Age, Customized >= 65 | 4 Participants |
| Sex: Female, Male Female | 94 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 89 / 103 |
| serious Total, serious adverse events | 27 / 103 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received investigational product. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of investigational product and 30 days after the last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.
Time frame: From start of study drug administration until week 182
Population: Safety Population included all participants who received at least one dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 101 participants |
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 27 participants |
Secondary
Accumulation Index for Minimum Observed Serum Concentration (Ctrough) of Sifalimumab
The Ctrough is the minimum observed serum concentration of sifalimumab. Accumulation Index is calculated as Ctrough value at steady state divided by Ctrough value after first dose.
Time frame: Pre-infusion and End of Infusion on Day 1 and Week 2, 4, 8, 12, 24, 52, 104, 156 and 168
Population: The PK Population included all participants who received at least one dose of investigational product and had at least one evaluable sifalimumab serum concentration. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Accumulation Index for Minimum Observed Serum Concentration (Ctrough) of Sifalimumab | 1.217 ratio | Standard Deviation 0.808 |
Secondary
Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCtau) of Sifalimumab
The AUCtau is the area under the serum concentration-time curve over the dosing interval of sifalimumab.
Time frame: Pre-infusion and End of Infusion on Day 1
Population: The PK Population included all participants who received at least one dose of investigational product and had at least one evaluable sifalimumab serum concentration. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCtau) of Sifalimumab | 2084.180 microgram.day per milliliter(mcg*day/mL) | Standard Deviation 665.882 |
Secondary
Maximum Observed Serum Concentration (Cmax) for Sifalimumab
The Cmax is the maximum observed plasma concentration of sifalimumab.
Time frame: Pre-infusion and End of Infusion on Day 1
Population: The PK Population included all participants who received at least one dose of investigational product and had at least one evaluable sifalimumab serum concentration. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Maximum Observed Serum Concentration (Cmax) for Sifalimumab | 225.569 microgram per milliliter (mcg/mL) | Standard Deviation 78.842 |
Secondary
Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Sifalimumab
The Ctrough is the minimum observed serum concentration at steady state of sifalimumab.
Time frame: Pre-infusion and End of Infusion on Day 1 and Week 2, 4, 8, 12, 24, 52, 104, 156 and 168
Population: The PK Population included all participants who received at least one dose of investigational product and had at least one evaluable sifalimumab serum concentration. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Sifalimumab | 78.731 mcg/mL | Standard Deviation 53.942 |
Secondary
Minimum Observed Serum Concentration (Ctrough) of Sifalimumab
The Ctrough is the minimum observed serum concentration of sifalimumab.
Time frame: Pre-infusion and End of Infusion on Day 1
Population: The PK Population included all participants who received at least one dose of investigational product and had at least one evaluable sifalimumab serum concentration. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Minimum Observed Serum Concentration (Ctrough) of Sifalimumab | 65.009 mcg/mL | Standard Deviation 30.516 |
Secondary
Number of Participants With Positive Anti-Drug Antibody
Participants tested for immunogenicity to Sifalimumab (MEDI-545) from Day 1 to the end of study.
Time frame: Day 1 and Week 12, 24, 52, 104, 156 and 168
Population: Safety Population included all participants who received at least one dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Positive Anti-Drug Antibody | Day 1 | 5 Participants |
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Positive Anti-Drug Antibody | Week 12 | 0 Participants |
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Positive Anti-Drug Antibody | Week 24 | 0 Participants |
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Positive Anti-Drug Antibody | Week 52 | 1 Participants |
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Positive Anti-Drug Antibody | Week 104 | 4 Participants |
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Positive Anti-Drug Antibody | Week 156 | 1 Participants |
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Positive Anti-Drug Antibody | Week 168 | 4 Participants |
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Number of Participants With Positive Anti-Drug Antibody | Any Day Post Baseline | 9 Participants |
Secondary
Time to Last Quantifiable Plasma Concentration (Tlast) of Sifalimumab
The Tlast is the time to last quantifiable plasma concentration (Tlast) of sifalimumab.
Time frame: Pre-infusion and End of Infusion on Day 1
Population: The PK Population included all participants who received at least one dose of investigational product and had at least one evaluable sifalimumab serum concentration. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Time to Last Quantifiable Plasma Concentration (Tlast) of Sifalimumab | 14.413 days | Standard Deviation 1.693 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sifalimumab
The Tmax is the time to reach maximum observed plasma concentration of sifalimumab.
Time frame: Pre-infusion and End of Infusion on Day 1
Population: The PK Population included all participants who received at least one dose of investigational product and had at least one evaluable sifalimumab serum concentration. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sifalimumab (MEDI-545) 500 or 600 Milligram (mg) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sifalimumab | 0.049 days |