Giant Cell Arteritis
Conditions
Brief summary
This study will evaluate the pharmacokinetics, pharmacodynamics, and safety of two dose levels of tocilizumab (TCZ) administered by intravenous (IV) infusion every 4 weeks (Q4W) to participants with giant cell arteritis (GCA).
Interventions
DRUGTocilizumab
TCZ will be administered by IV infusion at two dose levels Q4W. The maximum dose of TCZ that will be administered is 800 mg. The dose of TCZ infusion will be calculated on the basis of body weight measured prior to each infusion.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of GCA as classified according to protocol-specified criteria; * Participants entering Period 1 must be receiving treatment with TCZ 8 mg/kg IV Q4W.
Exclusion criteria
* Treatment with any other investigational agent besides TCZ within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) prior to screening; * Evidence of serious uncontrolled disease; * Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections; * Active TB requiring treatment within the previous 3 years.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events | Baseline - Day 151 |
| Maximum Serum Concentration (Cmax) of TCZ | Baseline; Weeks 4, 8, 12, 16-24 |
| Trough Serum Concentration (Ctrough) of TCZ at Steady State | Baseline; Weeks 4, 8, 12, 16-24 |
| Area Under the Concentration-Time Curve Over the Dosing Interval of 4 Weeks (AUC4weeks) of TCZ at Steady State | Baseline; Weeks 4, 8, 12, 16-24 |
Secondary
| Measure | Time frame |
|---|---|
| Serum Concentration of Interleukin-6 (IL-6) | Baseline; Weeks 12, 16, 20, 24 |
| Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Baseline; Weeks 12, 16, 20, 24 |
| Serum Concentration of C-Reactive Protein (CRP) | Baseline; Weeks 4, 8, 12, 16-24 |
| Erythrocyte Sedimentation Rate (ESR) | Baseline; Weeks 4, 8, 12, 16-24 |
Countries
Switzerland
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 | Adverse Event | 1 |
| Period 1 | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | TCZ IV Q4W |
|---|---|
| Age, Continuous | 67.9 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 22 |
| other Total, other adverse events | 6 / 24 | 3 / 22 |
| serious Total, serious adverse events | 3 / 24 | 1 / 22 |
Outcome results
Primary
Area Under the Concentration-Time Curve Over the Dosing Interval of 4 Weeks (AUC4weeks) of TCZ at Steady State
Time frame: Baseline; Weeks 4, 8, 12, 16-24
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TCZ IV Q4W 7 mg/kg | Area Under the Concentration-Time Curve Over the Dosing Interval of 4 Weeks (AUC4weeks) of TCZ at Steady State | 2130 day*ug/mL |
| TCZ IV Q4W 6 mg/kg | Area Under the Concentration-Time Curve Over the Dosing Interval of 4 Weeks (AUC4weeks) of TCZ at Steady State | 1610 day*ug/mL |
Primary
Maximum Serum Concentration (Cmax) of TCZ
Time frame: Baseline; Weeks 4, 8, 12, 16-24
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TCZ IV Q4W 7 mg/kg | Maximum Serum Concentration (Cmax) of TCZ | 197 ug/mL |
| TCZ IV Q4W 6 mg/kg | Maximum Serum Concentration (Cmax) of TCZ | 178 ug/mL |
Primary
Percentage of Participants With Adverse Events
Time frame: Baseline - Day 151
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCZ IV Q4W 7 mg/kg | Percentage of Participants With Adverse Events | 79.2 Percentage of Participants |
| TCZ IV Q4W 6 mg/kg | Percentage of Participants With Adverse Events | 40.9 Percentage of Participants |
Primary
Trough Serum Concentration (Ctrough) of TCZ at Steady State
Time frame: Baseline; Weeks 4, 8, 12, 16-24
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TCZ IV Q4W 7 mg/kg | Trough Serum Concentration (Ctrough) of TCZ at Steady State | 37.2 ug/mL |
| TCZ IV Q4W 6 mg/kg | Trough Serum Concentration (Ctrough) of TCZ at Steady State | 22.7 ug/mL |
Secondary
Erythrocyte Sedimentation Rate (ESR)
Time frame: Baseline; Weeks 4, 8, 12, 16-24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Baseline | 6.1 mm/h | Standard Deviation 6.72 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 16 | 5.9 mm/h | Standard Deviation 4.56 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 17 | 5.2 mm/h | Standard Deviation 3.84 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 18 | 4.4 mm/h | Standard Deviation 3.99 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 19 | 4.3 mm/h | Standard Deviation 2.64 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 20 | 7.1 mm/h | Standard Deviation 6.19 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 21 | 4.5 mm/h | Standard Deviation 3.54 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 22 | 5.3 mm/h | Standard Deviation 3.79 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 23 | 4.0 mm/h | Standard Deviation 3 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 24 | 3.7 mm/h | Standard Deviation 1.53 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 4 | 4.7 mm/h | Standard Deviation 3.38 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 8 | 7.2 mm/h | Standard Deviation 12.25 |
| TCZ IV Q4W 7 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 12 | 5.9 mm/h | Standard Deviation 5.3 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Baseline | 5.6 mm/h | Standard Deviation 5.01 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 20 | 5.6 mm/h | Standard Deviation 5.04 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 4 | 5.6 mm/h | Standard Deviation 4.11 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 17 | 5.0 mm/h | Standard Deviation 4.64 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 8 | 5.0 mm/h | Standard Deviation 3.13 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 19 | 5.0 mm/h | Standard Deviation 5.2 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 12 | 6.5 mm/h | Standard Deviation 5.27 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 18 | 4.8 mm/h | Standard Deviation 3.01 |
| TCZ IV Q4W 6 mg/kg | Erythrocyte Sedimentation Rate (ESR) | Week 16 | 5.1 mm/h | Standard Deviation 4.32 |
Secondary
Serum Concentration of C-Reactive Protein (CRP)
Time frame: Baseline; Weeks 4, 8, 12, 16-24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 24 | 0.200 mg/L | Standard Deviation 0 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Baseline | 0.615 mg/L | Standard Deviation 1.1645 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 12 | 0.467 mg/L | Standard Deviation 0.5694 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 16 | 0.344 mg/L | Standard Deviation 0.2795 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 17 | 0.409 mg/L | Standard Deviation 0.2533 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 18 | 0.374 mg/L | Standard Deviation 0.2994 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 19 | 0.387 mg/L | Standard Deviation 0.2801 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 21 | 0.200 mg/L | Standard Deviation 0 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 22 | 0.200 mg/L | Standard Deviation 0 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 23 | 0.203 mg/L | Standard Deviation 0.0058 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 20 | 0.340 mg/L | Standard Deviation 0.2172 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 4 | 0.511 mg/L | Standard Deviation 0.7538 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 8 | 0.426 mg/L | Standard Deviation 0.3687 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Baseline | 0.356 mg/L | Standard Deviation 0.2486 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 20 | 0.416 mg/L | Standard Deviation 0.2938 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 4 | 0.591 mg/L | Standard Deviation 1.0646 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 17 | 0.409 mg/L | Standard Deviation 0.4521 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 8 | 0.403 mg/L | Standard Deviation 0.3217 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 19 | 0.388 mg/L | Standard Deviation 0.3348 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 12 | 0.359 mg/L | Standard Deviation 0.2585 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 18 | 0.389 mg/L | Standard Deviation 0.3168 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of C-Reactive Protein (CRP) | Week 16 | 0.382 mg/L | Standard Deviation 0.3726 |
Secondary
Serum Concentration of Interleukin-6 (IL-6)
Time frame: Baseline; Weeks 12, 16, 20, 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Week 24 | 111.00 pg/mL | — |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Week 12 | 56.03 pg/mL | Standard Deviation 84.988 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Week 16 | 97.57 pg/mL | Standard Deviation 277.409 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Week 20 | 38.11 pg/mL | Standard Deviation 21.147 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Baseline | 57.80 pg/mL | Standard Deviation 61.149 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Baseline | 39.46 pg/mL | Standard Deviation 25.989 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Week 16 | 43.04 pg/mL | Standard Deviation 54.232 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Week 12 | 49.73 pg/mL | Standard Deviation 81.718 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of Interleukin-6 (IL-6) | Week 20 | 46.97 pg/mL | Standard Deviation 61.454 |
Secondary
Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R)
Time frame: Baseline; Weeks 12, 16, 20, 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Week 24 | 519.0 ng/mL | — |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Week 16 | 654.6 ng/mL | Standard Deviation 173.26 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Baseline | 665.8 ng/mL | Standard Deviation 153.81 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Week 12 | 680.8 ng/mL | Standard Deviation 183.84 |
| TCZ IV Q4W 7 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Week 20 | 663.8 ng/mL | Standard Deviation 147.92 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Week 16 | 651.7 ng/mL | Standard Deviation 136.95 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Week 12 | 670.9 ng/mL | Standard Deviation 175.92 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Baseline | 671.3 ng/mL | Standard Deviation 152.69 |
| TCZ IV Q4W 6 mg/kg | Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) | Week 20 | 690.0 ng/mL | Standard Deviation 215.91 |