Trial Outcomes & Findings for Safety and Tolerability of Intravenous Dose of MEDI-546 in Japanese Subjects With Systemic Lupus Erythematosus. (NCT NCT01559090)
NCT ID: NCT01559090
Last Updated: 2019-03-13
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
17 participants
Primary outcome timeframe
Stage I (up to 48 weeks)
Results posted on
2019-03-13
Participant Flow
Participant milestones
| Measure |
MEDI-546 100 mg IV
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
|---|---|---|---|
|
Stage I
STARTED
|
6
|
5
|
6
|
|
Stage I
COMPLETED
|
4
|
3
|
3
|
|
Stage I
NOT COMPLETED
|
2
|
2
|
3
|
|
Stage II
STARTED
|
4
|
3
|
2
|
|
Stage II
COMPLETED
|
3
|
3
|
2
|
|
Stage II
NOT COMPLETED
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
MEDI-546 100 mg IV
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
|---|---|---|---|
|
Stage I
Withdrawal by Subject
|
2
|
2
|
3
|
|
Stage II
Withdrawal by Subject
|
1
|
0
|
0
|
Baseline Characteristics
Safety and Tolerability of Intravenous Dose of MEDI-546 in Japanese Subjects With Systemic Lupus Erythematosus.
Baseline characteristics by cohort
| Measure |
MEDI-546 100 mg IV
n=6 Participants
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
n=5 Participants
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
n=6 Participants
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
43 years
STANDARD_DEVIATION 12 • n=5 Participants
|
34 years
STANDARD_DEVIATION 11 • n=7 Participants
|
37 years
STANDARD_DEVIATION 10 • n=5 Participants
|
38 years
STANDARD_DEVIATION 11 • n=4 Participants
|
|
Sex/Gender, Customized
Male
|
0 male/female
n=5 Participants
|
1 male/female
n=7 Participants
|
0 male/female
n=5 Participants
|
16 male/female
n=4 Participants
|
|
Sex/Gender, Customized
Female
|
6 male/female
n=5 Participants
|
4 male/female
n=7 Participants
|
6 male/female
n=5 Participants
|
1 male/female
n=4 Participants
|
PRIMARY outcome
Timeframe: Stage I (up to 48 weeks)Outcome measures
| Measure |
MEDI-546 100 mg IV
n=6 Participants
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
n=5 Participants
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
n=6 Participants
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
|---|---|---|---|
|
Overall Summary of Adverse Events
Any AE
|
6 Participants
|
5 Participants
|
6 Participants
|
|
Overall Summary of Adverse Events
Any AE of grade 3 or higher
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Overall Summary of Adverse Events
Any AE with outcome=death
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Overall Summary of Adverse Events
Any SAE
|
2 Participants
|
2 Participants
|
3 Participants
|
|
Overall Summary of Adverse Events
Any AE leading to discontinuation of IP
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Overall Summary of Adverse Events
Any causally related AE
|
5 Participants
|
4 Participants
|
4 Participants
|
|
Overall Summary of Adverse Events
Any other significant AE
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29Outcome measures
| Measure |
MEDI-546 100 mg IV
n=6 Participants
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
n=5 Participants
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
n=6 Participants
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
|---|---|---|---|
|
Pharmacokinetic Parameters of MEDI-546 After Single Dose: Cmax
|
41.1 ug/mL
Geometric Coefficient of Variation 27.6
|
75.1 ug/mL
Geometric Coefficient of Variation 12.5
|
254.8 ug/mL
Geometric Coefficient of Variation 20.7
|
SECONDARY outcome
Timeframe: Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29Outcome measures
| Measure |
MEDI-546 100 mg IV
n=6 Participants
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
n=5 Participants
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
n=6 Participants
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
|---|---|---|---|
|
Pharmacokinetic Parameters of MEDI-546 After Single Dose: AUClast
|
221.5 ug.day/mL
Geometric Coefficient of Variation 18.8
|
666.5 ug.day/mL
Geometric Coefficient of Variation 36.8
|
3151.9 ug.day/mL
Geometric Coefficient of Variation 14.6
|
SECONDARY outcome
Timeframe: Stage I (up to Week 48)MEDI-546 antibody detection measured by electrochemiluminescence (ECL).
Outcome measures
| Measure |
MEDI-546 100 mg IV
n=6 Participants
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
n=5 Participants
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
n=6 Participants
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
|---|---|---|---|
|
Anti-drug Antibody (ADA)
Positive
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Anti-drug Antibody (ADA)
Negative
|
5 Participants
|
4 Participants
|
5 Participants
|
Adverse Events
MEDI-546 100 mg IV
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
MEDI-546 300 mg IV
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
MEDI-546 1000 mg IV
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MEDI-546 100 mg IV
n=6 participants at risk
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
n=5 participants at risk
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
n=6 participants at risk
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
|
0.00%
0/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Gastrointestinal disorders
Acute abdomen
|
16.7%
1/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
|
General disorders
Chest pain
|
0.00%
0/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Infections and infestations
Cellulitis
|
0.00%
0/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
|
Nervous system disorders
Cerebral infarction
|
16.7%
1/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
|
Pregnancy, puerperium and perinatal conditions
Abortion
|
0.00%
0/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
Other adverse events
| Measure |
MEDI-546 100 mg IV
n=6 participants at risk
Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 300 mg IV
n=5 participants at risk
Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks
|
MEDI-546 1000 mg IV
n=6 participants at risk
Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV
|
|---|---|---|---|
|
Infections and infestations
Nsopharyngitis
|
50.0%
3/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
66.7%
4/6 • Stage I: 337 to 422 days
|
|
Infections and infestations
Upper respiratory tract infection
|
33.3%
2/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Infections and infestations
Bronchitis
|
16.7%
1/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
|
Infections and infestations
Folliculitis
|
16.7%
1/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Infections and infestations
Gastroenteritis
|
33.3%
2/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/6 • Stage I: 337 to 422 days
|
40.0%
2/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
|
Infections and infestations
Influenza
|
16.7%
1/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.7%
1/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
33.3%
2/6 • Stage I: 337 to 422 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
General disorders
Fatigue
|
16.7%
1/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
16.7%
1/6 • Stage I: 337 to 422 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
16.7%
1/6 • Stage I: 337 to 422 days
|
20.0%
1/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
|
Vascular disorders
Hypertension
|
33.3%
2/6 • Stage I: 337 to 422 days
|
0.00%
0/5 • Stage I: 337 to 422 days
|
0.00%
0/6 • Stage I: 337 to 422 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place