Clinical trial NCT00979654: A Study to Evaluate the Long-Term Safety of MEDI-545 in Adult Participants With Systemic Lupus Erythematosus or Myositis
Official title: A Phase 2 Open-label Study to Evaluate the Long-term Safety of Sifalimumab in Adult Subjects With Systemic Lupus Erythematosus or Myositis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: Sifalimumab
MEDI-545
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
First posted: 2009-09-18
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From start of study drug administration until week 182
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) for Sifalimumab
timeFrame: Pre-infusion and End of Infusion on Day 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sifalimumab
timeFrame: Pre-infusion and End of Infusion on Day 1
measure: Time to Last Quantifiable Plasma Concentration (Tlast) of Sifalimumab
timeFrame: Pre-infusion and End of Infusion on Day 1
measure: Minimum Observed Serum Concentration (Ctrough) of Sifalimumab
timeFrame: Pre-infusion and End of Infusion on Day 1
measure: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCtau) of Sifalimumab
timeFrame: Pre-infusion and End of Infusion on Day 1
measure: Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Sifalimumab
timeFrame: Pre-infusion and End of Infusion on Day 1 and Week 2, 4, 8, 12, 24, 52, 104, 156 and 168
measure: Accumulation Index for Minimum Observed Serum Concentration (Ctrough) of Sifalimumab
timeFrame: Pre-infusion and End of Infusion on Day 1 and Week 2, 4, 8, 12, 24, 52, 104, 156 and 168
measure: Number of Participants With Positive Anti-Drug Antibody
timeFrame: Day 1 and Week 12, 24, 52, 104, 156 and 168
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: San Leandro
country: United States
facility: Research Site
state: California
city: Upland
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Fort Lauderdale
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Cumberland
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Lansing
country: United States
facility: Research Site
state: Michigan
city: Lake Success
country: United States
facility: Research Site
state: New York
city: Manhasset
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Columbia
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Curitiba
country: Brazil
facility: Research Site
city: Sao Paolo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: Santiago
country: Chile
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Jerry Green
role: STUDY_DIRECTOR
References: