A Study to Evaluate the Long-Term Safety of MEDI-545 in Adult Participants With Systemic Lupus Erythematosus or Myositis

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2 Open-label Study to Evaluate the Long-term Safety of Sifalimumab in Adult Subjects With Systemic Lupus Erythematosus or Myositis

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Sifalimumab


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sifalimumab (MEDI-545) 500 or 600 milligram (mg)<br>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. | Drug: Sifalimumab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From start of study drug administration until week 182 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) for Sifalimumab | The Cmax is the maximum observed plasma concentration of sifalimumab. | Pre-infusion and End of Infusion on Day 1 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sifalimumab | The Tmax is the time to reach maximum observed plasma concentration of sifalimumab. | Pre-infusion and End of Infusion on Day 1 | 
| Time to Last Quantifiable Plasma Concentration (Tlast) of Sifalimumab | The Tlast is the time to last quantifiable plasma concentration (Tlast) of sifalimumab. | Pre-infusion and End of Infusion on Day 1 | 
| Minimum Observed Serum Concentration (Ctrough) of Sifalimumab | The Ctrough is the minimum observed serum concentration of sifalimumab. | Pre-infusion and End of Infusion on Day 1 | 
| 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. | Pre-infusion and End of Infusion on Day 1 | 
| Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Sifalimumab | The Ctrough is the minimum observed serum concentration at steady state of sifalimumab. | Pre-infusion and End of Infusion on Day 1 and Week 2, 4, 8, 12, 24, 52, 104, 156 and 168 | 
| 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. | Pre-infusion and End of Infusion on Day 1 and Week 2, 4, 8, 12, 24, 52, 104, 156 and 168 | 
| Number of Participants With Positive Anti-Drug Antibody | Participants tested for immunogenicity to Sifalimumab (MEDI-545) from Day 1 to the end of study. | Day 1 and Week 12, 24, 52, 104, 156 and 168 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sifalimumab, MEDI-545