Trial Outcomes & Findings for A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab (TCZ) Administered to Participants With Giant Cell Arteritis (GCA). (NCT NCT03923738)
NCT ID: NCT03923738
Last Updated: 2021-12-22
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Baseline; Weeks 4, 8, 12, 16-24
Results posted on
2021-12-22
Participant Flow
Participants from Period 1 (n=24) that completed the Period and reached remission entered Period 2 (n=22). Two participants withdrew prior to entering Period 2.
Participant milestones
| Measure |
TCZ IV Q4W
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg IV TCZ Q4W prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W in Period 1. Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W in Period 2.
|
|---|---|
|
Period 1
STARTED
|
24
|
|
Period 1
COMPLETED
|
22
|
|
Period 1
NOT COMPLETED
|
2
|
|
Period 2
STARTED
|
22
|
|
Period 2
COMPLETED
|
22
|
|
Period 2
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
TCZ IV Q4W
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg IV TCZ Q4W prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W in Period 1. Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W in Period 2.
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|---|---|
|
Period 1
Adverse Event
|
1
|
|
Period 1
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab (TCZ) Administered to Participants With Giant Cell Arteritis (GCA).
Baseline characteristics by cohort
| Measure |
TCZ IV Q4W
n=24 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg IV TCZ Q4W prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W in Period 1. Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W in Period 2.
|
|---|---|
|
Age, Continuous
|
67.9 Years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline; Weeks 4, 8, 12, 16-24Population: The pharmacokinetic (PK) population consisted of participants who received one dose of TCZ and had one valid PK sample, with participants grouped according to treatment received.
Outcome measures
| Measure |
TCZ IV Q4W 7 mg/kg
n=21 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV Q4W 6 mg/kg
n=22 Participants
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
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|---|---|---|
|
Maximum Serum Concentration (Cmax) of TCZ
|
197 ug/mL
Interval 118.0 to 352.0
|
178 ug/mL
Interval 115.0 to 320.0
|
PRIMARY outcome
Timeframe: Baseline; Weeks 4, 8, 12, 16-24Population: The pharmacokinetic (PK) population consisted of participants who received one dose of TCZ and had one valid PK sample, with participants grouped according to treatment received.
Outcome measures
| Measure |
TCZ IV Q4W 7 mg/kg
n=22 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV Q4W 6 mg/kg
n=22 Participants
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
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|---|---|---|
|
Trough Serum Concentration (Ctrough) of TCZ at Steady State
|
37.2 ug/mL
Interval 6.59 to 69.0
|
22.7 ug/mL
Interval 3.38 to 54.5
|
PRIMARY outcome
Timeframe: Baseline; Weeks 4, 8, 12, 16-24Population: The pharmacokinetic (PK) population consisted of participants who received one dose of TCZ and had one valid PK sample, with participants grouped according to treatment received.
Outcome measures
| Measure |
TCZ IV Q4W 7 mg/kg
n=22 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV Q4W 6 mg/kg
n=22 Participants
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
|
|---|---|---|
|
Area Under the Concentration-Time Curve Over the Dosing Interval of 4 Weeks (AUC4weeks) of TCZ at Steady State
|
2130 day*ug/mL
Interval 1120.0 to 4300.0
|
1610 day*ug/mL
Interval 921.0 to 3070.0
|
PRIMARY outcome
Timeframe: Baseline - Day 151Outcome measures
| Measure |
TCZ IV Q4W 7 mg/kg
n=24 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV Q4W 6 mg/kg
n=22 Participants
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
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|---|---|---|
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Percentage of Participants With Adverse Events
|
79.2 Percentage of Participants
|
40.9 Percentage of Participants
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SECONDARY outcome
Timeframe: Baseline; Weeks 12, 16, 20, 24Population: The pharmacodynamic (PD) population was identical to the safety analysis population, which consisted of participants who received at least one dose of study drug and had at least one safety assessment.
Outcome measures
| Measure |
TCZ IV Q4W 7 mg/kg
n=24 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV Q4W 6 mg/kg
n=22 Participants
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
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|---|---|---|
|
Serum Concentration of Interleukin-6 (IL-6)
Baseline
|
57.80 pg/mL
Standard Deviation 61.149
|
39.46 pg/mL
Standard Deviation 25.989
|
|
Serum Concentration of Interleukin-6 (IL-6)
Week 12
|
56.03 pg/mL
Standard Deviation 84.988
|
49.73 pg/mL
Standard Deviation 81.718
|
|
Serum Concentration of Interleukin-6 (IL-6)
Week 16
|
97.57 pg/mL
Standard Deviation 277.409
|
43.04 pg/mL
Standard Deviation 54.232
|
|
Serum Concentration of Interleukin-6 (IL-6)
Week 20
|
38.11 pg/mL
Standard Deviation 21.147
|
46.97 pg/mL
Standard Deviation 61.454
|
|
Serum Concentration of Interleukin-6 (IL-6)
Week 24
|
111.00 pg/mL
Standard Deviation NA
SD is NA for n=1
|
—
|
SECONDARY outcome
Timeframe: Baseline; Weeks 12, 16, 20, 24Population: The pharmacodynamic (PD) population was identical to the safety analysis population, which consisted of participants who received at least one dose of study drug and had at least one safety assessment.
Outcome measures
| Measure |
TCZ IV Q4W 7 mg/kg
n=24 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV Q4W 6 mg/kg
n=22 Participants
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
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|---|---|---|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R)
Baseline
|
665.8 ng/mL
Standard Deviation 153.81
|
671.3 ng/mL
Standard Deviation 152.69
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R)
Week 12
|
680.8 ng/mL
Standard Deviation 183.84
|
670.9 ng/mL
Standard Deviation 175.92
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R)
Week 16
|
654.6 ng/mL
Standard Deviation 173.26
|
651.7 ng/mL
Standard Deviation 136.95
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R)
Week 20
|
663.8 ng/mL
Standard Deviation 147.92
|
690.0 ng/mL
Standard Deviation 215.91
|
|
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R)
Week 24
|
519.0 ng/mL
Standard Deviation NA
SD is NA for n=1
|
—
|
SECONDARY outcome
Timeframe: Baseline; Weeks 4, 8, 12, 16-24Population: The pharmacodynamic (PD) population was identical to the safety analysis population, which consisted of participants who received at least one dose of study drug and had at least one safety assessment.
Outcome measures
| Measure |
TCZ IV Q4W 7 mg/kg
n=24 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV Q4W 6 mg/kg
n=22 Participants
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
|
|---|---|---|
|
Serum Concentration of C-Reactive Protein (CRP)
Baseline
|
0.615 mg/L
Standard Deviation 1.1645
|
0.356 mg/L
Standard Deviation 0.2486
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 4
|
0.511 mg/L
Standard Deviation 0.7538
|
0.591 mg/L
Standard Deviation 1.0646
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 8
|
0.426 mg/L
Standard Deviation 0.3687
|
0.403 mg/L
Standard Deviation 0.3217
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 12
|
0.467 mg/L
Standard Deviation 0.5694
|
0.359 mg/L
Standard Deviation 0.2585
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 16
|
0.344 mg/L
Standard Deviation 0.2795
|
0.382 mg/L
Standard Deviation 0.3726
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 17
|
0.409 mg/L
Standard Deviation 0.2533
|
0.409 mg/L
Standard Deviation 0.4521
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 18
|
0.374 mg/L
Standard Deviation 0.2994
|
0.389 mg/L
Standard Deviation 0.3168
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 19
|
0.387 mg/L
Standard Deviation 0.2801
|
0.388 mg/L
Standard Deviation 0.3348
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 20
|
0.340 mg/L
Standard Deviation 0.2172
|
0.416 mg/L
Standard Deviation 0.2938
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 21
|
0.200 mg/L
Standard Deviation 0.0000
|
—
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 22
|
0.200 mg/L
Standard Deviation 0.0000
|
—
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 23
|
0.203 mg/L
Standard Deviation 0.0058
|
—
|
|
Serum Concentration of C-Reactive Protein (CRP)
Week 24
|
0.200 mg/L
Standard Deviation 0.0000
|
—
|
SECONDARY outcome
Timeframe: Baseline; Weeks 4, 8, 12, 16-24Population: The pharmacodynamic (PD) population was identical to the safety analysis population, which consisted of participants who received at least one dose of study drug and had at least one safety assessment.
Outcome measures
| Measure |
TCZ IV Q4W 7 mg/kg
n=24 Participants
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV Q4W 6 mg/kg
n=22 Participants
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
|
|---|---|---|
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Erythrocyte Sedimentation Rate (ESR)
Baseline
|
6.1 mm/h
Standard Deviation 6.72
|
5.6 mm/h
Standard Deviation 5.01
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 4
|
4.7 mm/h
Standard Deviation 3.38
|
5.6 mm/h
Standard Deviation 4.11
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 8
|
7.2 mm/h
Standard Deviation 12.25
|
5.0 mm/h
Standard Deviation 3.13
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 12
|
5.9 mm/h
Standard Deviation 5.30
|
6.5 mm/h
Standard Deviation 5.27
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 16
|
5.9 mm/h
Standard Deviation 4.56
|
5.1 mm/h
Standard Deviation 4.32
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 17
|
5.2 mm/h
Standard Deviation 3.84
|
5.0 mm/h
Standard Deviation 4.64
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 18
|
4.4 mm/h
Standard Deviation 3.99
|
4.8 mm/h
Standard Deviation 3.01
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 19
|
4.3 mm/h
Standard Deviation 2.64
|
5.0 mm/h
Standard Deviation 5.20
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 20
|
7.1 mm/h
Standard Deviation 6.19
|
5.6 mm/h
Standard Deviation 5.04
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 21
|
4.5 mm/h
Standard Deviation 3.54
|
—
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 22
|
5.3 mm/h
Standard Deviation 3.79
|
—
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 23
|
4.0 mm/h
Standard Deviation 3.00
|
—
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 24
|
3.7 mm/h
Standard Deviation 1.53
|
—
|
Adverse Events
TCZ IV 7 mg/kg Q4W
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
TCZ IV 6 mg/kg Q4W
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TCZ IV 7 mg/kg Q4W
n=24 participants at risk
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV 6 mg/kg Q4W
n=22 participants at risk
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/24 • Baseline - Day 151
|
4.5%
1/22 • Number of events 1 • Baseline - Day 151
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
4.2%
1/24 • Number of events 1 • Baseline - Day 151
|
0.00%
0/22 • Baseline - Day 151
|
|
Infections and infestations
Pneumonia pneumococcal
|
4.2%
1/24 • Number of events 1 • Baseline - Day 151
|
0.00%
0/22 • Baseline - Day 151
|
|
Vascular disorders
Aortic aneurysm rupture
|
4.2%
1/24 • Number of events 1 • Baseline - Day 151
|
0.00%
0/22 • Baseline - Day 151
|
Other adverse events
| Measure |
TCZ IV 7 mg/kg Q4W
n=24 participants at risk
Participants with GCA who received at least 5 consecutive doses of 8 mg/kg TCZ prior to baseline and reached remission received 5 or 6 consecutive doses of 7 mg/kg IV TCZ Q4W (Period 1).
|
TCZ IV 6 mg/kg Q4W
n=22 participants at risk
Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
12.5%
3/24 • Number of events 3 • Baseline - Day 151
|
4.5%
1/22 • Number of events 1 • Baseline - Day 151
|
|
Infections and infestations
Respiratory tract infection viral
|
4.2%
1/24 • Number of events 1 • Baseline - Day 151
|
9.1%
2/22 • Number of events 2 • Baseline - Day 151
|
|
Infections and infestations
Upper respiratory tract infection
|
8.3%
2/24 • Number of events 2 • Baseline - Day 151
|
0.00%
0/22 • Baseline - Day 151
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER