Trial | NCT01031836  Report issue

Title

A Study to Evaluate Safety and Tolerability of IV or SC Dose of MEDI-545 in Patients With Systemic Lupus Erythematosus.
A Phase II, Multicenter, Open-Label, Dose-Escalation Study to Evaluate Safety and Tolerability of IV or SC Dose of MEDI-545, a Fully Human Monoclonal Antibody Directed Against Interferon Alpha Subtypes, in Japanese Patients Who Have Systemic Lupus Erythematosus (SLE)

  • Phase

    Phase 2

  • Study Type

    Interventional

  • Intervention/Treatment

    sifalimumab ...

  • Study Participants

    30
The purpose of the study is to evaluate the safety and tolerability of MEDI-545 in Japanese adult SLE patients. This will be done by collecting the data from 3 cohorts of IV doses and 1 cohort of SC doses.
Study Started
Nov 25
2009
Primary Completion
Nov 07
2012
Study Completion
Jul 11
2016
Results Posted
Nov 19
2018
Last Update
Nov 19
2018

Drug MEDI-545

Stage I: MEDI-545 1.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 1.0 mg/kg IV once every 2 weeks for a total of 79 doses.

Drug MEDI-545

Stage I: MEDI-545 3.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 3.0 mg/kg IV once every 2 weeks for a total of 79 doses

Drug MEDI-545

Stage I: MEDI-545 10.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 10.0 mg/kg IV once every 2 weeks for a total of 79 doses.

Drug MEDI-545

Stage I: MEDI-545 100 mg SC, on Day 1 and weekly or once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 100 mg SC once every 2 weeks for a total of 79 doses.

Drug MEDI-545

Stage I: MEDI-545 1,200 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 1,200 mg IV once every 4 weeks for a total of 40 doses

Drug MEDI-545 600

Stage I: MEDI-545 600 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 600 mg IV once every 4 weeks for a total of 40 doses.

MEDI-545 1.0 mg/kg Experimental

Cohort 1

MEDI-545 3.0 mg/kg Experimental

Cohort 2

MEDI-545 10.0 mg/kg Experimental

Cohort 3

MEDI-545 100 mg Experimental

Cohort 4

MEDI-545 600 mg Experimental

Cohort 5

MEDI-545 1,200 mg Experimental

Cohort 6

Criteria 

Inclusion Criteria:

Patients must have previously met ≥4 of the 11 revised ACR criteria
Have positive antinuclear antibody test (ANA) at ≥1:80 serum dilute in the past or at screening
Have at least 1 system with a score of A or 2 systems with a score of B on the BILAG index at screening, or have a SELENA-SLEDAI score ≥6

Exclusion Criteria:

Have received prednisone >20 mg/day (or an equivalent dose of another oral corticosteroid) within 14 days before Visit 2 (Day 1)

Have received the following medications within 28 days before Visit 2 (Day 1):

Systemic cyclophosphamide at any dose
Cyclosporine at any dose
Tacrolimus at any dose
Thalidomide at any dose
Mycophenolate mofetil >2 g/day
Methotrexate >15 mg/week
Azathioprine >2 mg/kg/day
Women who have a positive pregnancy test (serum hCG) at Visit 1

Summary

MEDI-545 1.0 mg/kg IV

MEDI-545 3.0 mg/kg IV

MEDI-545 10.0 mg/kg IV

MEDI-545 100 mg SC

MEDI-545 600 mg IV

MEDI-545 1200 mg IV

All Events

Event Type Organ System Event Term MEDI-545 1.0 mg/kg IV MEDI-545 3.0 mg/kg IV MEDI-545 10.0 mg/kg IV MEDI-545 100 mg SC MEDI-545 600 mg IV MEDI-545 1200 mg IV

Number of Participants With Each Category of Adverse Events in Stage I

MEDI-545 1.0 mg/kg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEID-545 3.0 mg/kg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEDI-545 10.0 mg/kg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEDI-545 100mg SC

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEDI-545 600mg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEDI-545 1200mg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

Number of Participants in Each Category of Adverse Events (AE) in Stage II

MEDI-545 1.0 mg/kg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEID-545 3.0 mg/kg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEDI-545 10.0 mg/kg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEDI-545 100mg SC

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEDI-545 600mg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

MEDI-545 1200mg IV

Any AE

Any AE leading to discontinuation of IP

Any AE of CTC grade at least 3

Any AE with outcome=death

Any causally related AE

Any serious adverse events (SAE)

Change From Baseline in 21-gene Signature Fold Change in Stage I

21-gene signature fold change is pharmacodynamics (PD) parameter measuring expression of type I IFN-inducible gene.

MEDI-545 1.0 mg/kg IV

Day 15

-1.4
fold change (Mean)
Standard Deviation: 2.56

Day 1 8 hours post-dose

-3.7
fold change (Mean)
Standard Deviation: 2.07

Day 29

0.03
fold change (Mean)
Standard Deviation: 2.54

Day 3

-2.57
fold change (Mean)
Standard Deviation: 2.61

MEID-545 3.0 mg/kg IV

Day 15

-1.11
fold change (Mean)
Standard Deviation: 5.99

Day 1 8 hours post-dose

-5.68
fold change (Mean)
Standard Deviation: 5.92

Day 29

-0.16
fold change (Mean)
Standard Deviation: 8.44

Day 3

-4.53
fold change (Mean)
Standard Deviation: 7.02

MEDI-545 10.0 mg/kg IV

Day 15

-0.41
fold change (Mean)
Standard Deviation: 1.60

Day 1 8 hours post-dose

-2.3
fold change (Mean)
Standard Deviation: 0.93

Day 29

-0.34
fold change (Mean)
Standard Deviation: 1.38

Day 3

-2.49
fold change (Mean)
Standard Deviation: 1.06

MEDI-545 100mg SC

Day 15

-0.59
fold change (Mean)
Standard Deviation: 1.69

Day 1 8 hours post-dose

-1.17
fold change (Mean)
Standard Deviation: 0.80

Day 29

-0.85
fold change (Mean)
Standard Deviation: 0.81

Day 3

-1.8
fold change (Mean)
Standard Deviation: 0.97

MEDI-545 600mg IV

Day 15

-1.61
fold change (Mean)
Standard Deviation: 1.23

Day 1 8 hours post-dose

-4.91
fold change (Mean)
Standard Deviation: 2.26

Day 29

-1.13
fold change (Mean)
Standard Deviation: 1.40

Day 3

-4.81
fold change (Mean)
Standard Deviation: 2.63

MEDI-545 1200mg IV

Day 15

-1.84
fold change (Mean)
Standard Deviation: 1.72

Day 1 8 hours post-dose

-3.44
fold change (Mean)
Standard Deviation: 1.77

Day 29

-1.27
fold change (Mean)
Standard Deviation: 2.46

Day 3

-3.37
fold change (Mean)
Standard Deviation: 1.69

AUC0-14 of MEDI-545 After First Dose in Stage I

Summary of area under the concentration-time curve from zero to Day 14.

MEDI-545 1.0 mg/kg IV

151.28
day*ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 19.3

MEID-545 3.0 mg/kg IV

432.26
day*ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 11.0

MEDI-545 10.0 mg/kg IV

1728.01
day*ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 16.8

MEDI-545 100mg SC

128.06
day*ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 56.1

MEDI-545 600mg IV

1965.44
day*ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 41.4

MEDI-545 1200mg IV

4583.55
day*ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 15.2

Number of Participants With Positive Anti-drug Antibody (ADA) During Stage I

MEDI-545 1.0 mg/kg IV

MEID-545 3.0 mg/kg IV

MEDI-545 10.0 mg/kg IV

MEDI-545 100mg SC

MEDI-545 600mg IV

MEDI-545 1200mg IV

Area Undre Curve (AUC) of MEDI-545 After First Dose in Stage I

MEDI-545 1.0 mg/kg IV

261.98
day*ug/mL (Median)
Full Range: 16.8

MEID-545 3.0 mg/kg IV

647.93
day*ug/mL (Median)
Full Range: 7.4

MEDI-545 10.0 mg/kg IV

3040.83
day*ug/mL (Median)
Full Range: 24.2

MEDI-545 100mg SC

239.16
day*ug/mL (Median)
Full Range: 239.16 to 239.16

MEDI-545 600mg IV

2308.44
day*ug/mL (Median)
Full Range: 2308.44 to 2308.44

MEDI-545 1200mg IV

5235.41
day*ug/mL (Median)
Full Range: 11.6

Maximum Observed Concentration (Cmax) of MEDI-545 After First Dose in Stage I

MEDI-545 1.0 mg/kg IV

29.04
ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 31.3

MEID-545 3.0 mg/kg IV

71.72
ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 19.6

MEDI-545 10.0 mg/kg IV

311.17
ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 19.0

MEDI-545 100mg SC

11.7
ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 61.1

MEDI-545 600mg IV

244.54
ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 47.4

MEDI-545 1200mg IV

607.64
ug/mL (Geometric Mean)
Geometric Coefficient of Variation: 16.1

Total

30
Participants

Age, Continuous

40
years (Mean)
Standard Deviation: 11

Sex: Female, Male

Stage I

MEDI-545 1.0 mg/kg IV

MEDI-545 3.0 mg/kg IV

MEDI-545 10.0 mg/kg IV

MEDI-545 100 mg SC

MEDI-545 600 mg IV

MEDI-545 1200 mg IV

Stage II

MEDI-545 1.0 mg/kg IV

MEDI-545 3.0 mg/kg IV

MEDI-545 10.0 mg/kg IV

MEDI-545 100 mg SC

MEDI-545 600 mg IV

MEDI-545 1200 mg IV

Drop/Withdrawal Reasons

MEDI-545 1.0 mg/kg IV

MEDI-545 3.0 mg/kg IV

MEDI-545 10.0 mg/kg IV

MEDI-545 100 mg SC

MEDI-545 600 mg IV

MEDI-545 1200 mg IV