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

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ClinicalTrials.gov Identifier: NCT00979654
Recruitment Status : Completed
First Posted : September 18, 2009
Results First Posted : August 23, 2016
Last Update Posted : October 27, 2016
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
MedImmune LLC

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Systemic Lupus Erythematosus
Intervention Drug: Sifalimumab
Enrollment 118
Recruitment Details  
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.
Arm/Group Title MEDI-545
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 103
Completed 67
Not Completed 36
Reason Not Completed
Lost to Follow-up             1
Withdrawal by Subject             22
Death             1
Lack of Efficacy             6
Adverse Event             1
Adverse Event of Diverticulitis             1
Per Principal Investigator’s Discretion             1
Patient Wanted to Pursue Other Treatment             1
Serious Adverse Event             1
Unfavorable Risk-Benefit Analysis             1
Arm/Group Title MEDI-545
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 103
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 103 participants
48.2  (9.9)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants
< 40 21
40 - <65 78
>= 65 4
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Female
94
  91.3%
Male
9
   8.7%
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least one dose of investigational product.
Arm/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 103
Measure Type: Number
Unit of Measure: participants
TEAEs 101
TESAEs 27
2.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) for Sifalimumab
Hide Description The Cmax is the maximum observed plasma concentration of sifalimumab.
Time Frame Pre-infusion and End of Infusion on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 94
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (mcg/mL)
225.569  (78.842)
3.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sifalimumab
Hide Description The Tmax is the time to reach maximum observed plasma concentration of sifalimumab.
Time Frame Pre-infusion and End of Infusion on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 94
Median (Full Range)
Unit of Measure: days
0.049
(0.04 to 0.13)
4.Secondary Outcome
Title Time to Last Quantifiable Plasma Concentration (Tlast) of Sifalimumab
Hide Description The Tlast is the time to last quantifiable plasma concentration (Tlast) of sifalimumab.
Time Frame Pre-infusion and End of Infusion on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 99
Mean (Standard Deviation)
Unit of Measure: days
14.413  (1.693)
5.Secondary Outcome
Title Minimum Observed Serum Concentration (Ctrough) of Sifalimumab
Hide Description The Ctrough is the minimum observed serum concentration of sifalimumab.
Time Frame Pre-infusion and End of Infusion on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 99
Mean (Standard Deviation)
Unit of Measure: mcg/mL
65.009  (30.516)
6.Secondary Outcome
Title Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCtau) of Sifalimumab
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: microgram.day per milliliter(mcg*day/mL)
2084.180  (665.882)
7.Secondary Outcome
Title Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Sifalimumab
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 87
Mean (Standard Deviation)
Unit of Measure: mcg/mL
78.731  (53.942)
8.Secondary Outcome
Title Accumulation Index for Minimum Observed Serum Concentration (Ctrough) of Sifalimumab
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 84
Mean (Standard Deviation)
Unit of Measure: ratio
1.217  (0.808)
9.Secondary Outcome
Title Number of Participants With Positive Anti-Drug Antibody
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least one dose of investigational product.
Arm/Group Title Sifalimumab (MEDI-545) 500 or 600 Milligram (mg)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 103
Measure Type: Number
Unit of Measure: Participants
Day 1 5
Week 12 0
Week 24 0
Week 52 1
Week 104 4
Week 156 1
Week 168 4
Any Day Post Baseline 9
Time Frame From start of study drug administration until week 182
Adverse Event Reporting Description The safety Population included all participants who received at least one dose of investigational product.
 
Arm/Group Title MEDI-545
Hide Arm/Group Description 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.
All-Cause Mortality
MEDI-545
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
MEDI-545
Affected / at Risk (%) # Events
Total   27/103 (26.21%)    
Cardiac disorders   
Atrial fibrillation  1  2/103 (1.94%)  2
Cardiac tamponade  1  1/103 (0.97%)  1
Myocardial infarction  1  1/103 (0.97%)  1
Pericardial effusion  1  1/103 (0.97%)  1
General disorders   
Mucosal inflammation  1  1/103 (0.97%)  1
Non-cardiac chest pain  1  1/103 (0.97%)  1
Infections and infestations   
Abscess limb  1  1/103 (0.97%)  1
Bone abscess  1  1/103 (0.97%)  1
Cellulitis  1  3/103 (2.91%)  3
Diverticulitis  1  2/103 (1.94%)  2
Enteritis infectious  1  1/103 (0.97%)  1
Herpes simplex meningitis  1  1/103 (0.97%)  1
Herpes zoster disseminated  1  1/103 (0.97%)  1
Intervertebral discitis  1  1/103 (0.97%)  1
Osteomyelitis  1  1/103 (0.97%)  1
Pneumonia  1  1/103 (0.97%)  1
Pneumonia streptococcal  1  1/103 (0.97%)  1
Staphylococcal bacteraemia  1  1/103 (0.97%)  1
Urinary tract infection  1  2/103 (1.94%)  2
Viral upper respiratory tract infection  1  1/103 (0.97%)  1
Injury, poisoning and procedural complications   
Fibula fracture  1  1/103 (0.97%)  1
Post procedural haemorrhage  1  1/103 (0.97%)  1
Spinal fracture  1  1/103 (0.97%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/103 (0.97%)  1
Back pain  1  1/103 (0.97%)  1
Cervical spinal stenosis  1  1/103 (0.97%)  1
Lumbar spinal stenosis  1  1/103 (0.97%)  1
Musculoskeletal chest pain  1  3/103 (2.91%)  3
Myositis  1  1/103 (0.97%)  1
Rotator cuff syndrome  1  1/103 (0.97%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Lung adenocarcinoma  1  1/103 (0.97%)  1
Nervous system disorders   
Cerebrovascular accident  1  1/103 (0.97%)  1
Psychiatric disorders   
Bipolar disorder  1  1/103 (0.97%)  1
Depression  1  1/103 (0.97%)  1
Suicidal ideation  1  1/103 (0.97%)  1
Renal and urinary disorders   
Nephrolithiasis  1  1/103 (0.97%)  1
Renal failure acute  1  1/103 (0.97%)  1
Renal failure chronic  1  1/103 (0.97%)  1
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/103 (0.97%)  1
Chronic obstructive pulmonary disease  1  1/103 (0.97%)  1
Pleurisy  1  1/103 (0.97%)  1
Vascular disorders   
Deep vein thrombosis  1  1/103 (0.97%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MEDI-545
Affected / at Risk (%) # Events
Total   89/103 (86.41%)    
Gastrointestinal disorders   
Abdominal pain  1  6/103 (5.83%)  8
Diarrhoea  1  16/103 (15.53%)  24
Gastrooesophageal reflux disease  1  6/103 (5.83%)  6
Nausea  1  20/103 (19.42%)  28
Vomiting  1  11/103 (10.68%)  17
General disorders   
Fatigue  1  8/103 (7.77%)  9
Immune system disorders   
Seasonal allergy  1  7/103 (6.80%)  7
Infections and infestations   
Bronchitis  1  23/103 (22.33%)  36
Gastroenteritis  1  7/103 (6.80%)  7
Gastroenteritis viral  1  6/103 (5.83%)  10
Herpes zoster  1  8/103 (7.77%)  8
Influenza  1  7/103 (6.80%)  10
Nasopharyngitis  1  22/103 (21.36%)  36
Sinusitis  1  18/103 (17.48%)  38
Upper respiratory tract infection  1  40/103 (38.83%)  65
Urinary tract infection  1  30/103 (29.13%)  62
Vulvovaginal mycotic infection  1  6/103 (5.83%)  13
Injury, poisoning and procedural complications   
Contusion  1  9/103 (8.74%)  12
Fall  1  6/103 (5.83%)  8
Metabolism and nutrition disorders   
Hypokalaemia  1  8/103 (7.77%)  13
Musculoskeletal and connective tissue disorders   
Arthralgia  1  22/103 (21.36%)  26
Back pain  1  12/103 (11.65%)  12
Muscle spasms  1  6/103 (5.83%)  6
Musculoskeletal chest pain  1  8/103 (7.77%)  8
Pain in extremity  1  6/103 (5.83%)  6
Systemic lupus erythematosus  1  7/103 (6.80%)  9
Nervous system disorders   
Dizziness  1  10/103 (9.71%)  14
Headache  1  22/103 (21.36%)  27
Psychiatric disorders   
Anxiety  1  7/103 (6.80%)  7
Depression  1  9/103 (8.74%)  11
Insomnia  1  6/103 (5.83%)  6
Respiratory, thoracic and mediastinal disorders   
Cough  1  14/103 (13.59%)  14
Skin and subcutaneous tissue disorders   
Pruritus  1  7/103 (6.80%)  8
Rash  1  8/103 (7.77%)  12
Vascular disorders   
Hypertension  1  9/103 (8.74%)  12
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
A business decision was made to discontinue the development of sifalimumab in favor of another type 1 interferon (IFN) inhibitor.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
Results Point of Contact
Name/Title: Jerry Green
Organization: MedImmune, LLC
Phone: 1-888-483-7729
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00979654     History of Changes
Other Study ID Numbers: MI-CP212
First Submitted: September 17, 2009
First Posted: September 18, 2009
Results First Submitted: July 12, 2016
Results First Posted: August 23, 2016
Last Update Posted: October 27, 2016