A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab (TCZ) Administered to Participants With Giant Cell Arteritis (GCA).

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03923738
• Collaborator: (none)
• Enrollment: 24
• Locations: 2
• Arm: 1
• Actual Duration (Months): 15.3
• Patients Per Site: 12
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Giant Cell Arteritis	Drug: Tocilizumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib, Open-Label, Dose-Ranging Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab Administered by Intravenous Infusion to Patients With Giant Cell Arteritis
• Actual Study Start Date: Aug 5, 2019
• Actual Primary Completion Date: Nov 12, 2020
• Actual Study Completion Date: Nov 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TCZ IV Q4W Participants will receive up to 6 doses of Dose 1 of TCZ IV Q4W followed by up to 6 doses of Dose 2 of TCZ IV Q4W.	Drug: Tocilizumab; 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.; Other Names: RoActemra/Actemra

Outcome Measures

Primary Outcome Measures

1. Maximum Serum Concentration (Cmax) of TCZ [Baseline; Weeks 4, 8, 12, 16-24]

2. Trough Serum Concentration (Ctrough) of TCZ at Steady State [Baseline; Weeks 4, 8, 12, 16-24]

3. 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]

4. Percentage of Participants With Adverse Events [Baseline - Day 151]

Secondary Outcome Measures

1. Serum Concentration of Interleukin-6 (IL-6) [Baseline; Weeks 12, 16, 20, 24]

2. Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) [Baseline; Weeks 12, 16, 20, 24]

3. Serum Concentration of C-Reactive Protein (CRP) [Baseline; Weeks 4, 8, 12, 16-24]

4. Erythrocyte Sedimentation Rate (ESR) [Baseline; Weeks 4, 8, 12, 16-24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitätsspital Basel; Rheumatologie	Basel		Switzerland	4031
2	Inselspital Bern; Rheumatologie; Klinische Immunologie und Allergologie	Bern		Switzerland	3010

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Sep 6, 2019
• Statistical Analysis Plan - Jan 11, 2021

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03923738
• Other Study ID Numbers: WP41152; 2018-004718-17
• First Posted: Apr 23, 2019
• Last Update Posted: Dec 22, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	TCZ IV Q4W
Arm/Group Description	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 Title: Period 1
STARTED	24
COMPLETED	22
NOT COMPLETED	2
Period Title: Period 1
STARTED	22
COMPLETED	22
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	TCZ IV Q4W
Arm/Group Description	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.
Overall Participants	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.9 (8.1)
Sex: Female, Male (Count of Participants)
Female	15 62.5%
Male	9 37.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	23 95.8%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Serum Concentration (Cmax) of TCZ
Time Frame	Baseline; Weeks 4, 8, 12, 16-24

Outcome Measure Data

Analysis Population Description

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/Group Title	TCZ IV Q4W 7 mg/kg	TCZ IV Q4W 6 mg/kg
Arm/Group Description	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).	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
Measure Participants	21	22
Median (Full Range) [ug/mL]	197	178

2. Primary Outcome

Title	Trough Serum Concentration (Ctrough) of TCZ at Steady State
Time Frame	Baseline; Weeks 4, 8, 12, 16-24

Outcome Measure Data

Analysis Population Description

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/Group Title	TCZ IV Q4W 7 mg/kg	TCZ IV Q4W 6 mg/kg
Arm/Group Description	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).	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
Measure Participants	22	22
Median (Full Range) [ug/mL]	37.2	22.7

3. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TCZ IV Q4W 7 mg/kg	TCZ IV Q4W 6 mg/kg
Arm/Group Description	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).	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
Measure Participants	22	22
Median (Full Range) [day*ug/mL]	2130	1610

4. Primary Outcome

Title	Percentage of Participants With Adverse Events
Time Frame	Baseline - Day 151

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TCZ IV Q4W 7 mg/kg	TCZ IV Q4W 6 mg/kg
Arm/Group Description	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).	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
Measure Participants	24	22
Number [Percentage of Participants]	79.2 330%	40.9 NaN

5. Secondary Outcome

Title	Serum Concentration of Interleukin-6 (IL-6)
Time Frame	Baseline; Weeks 12, 16, 20, 24

Outcome Measure Data

Analysis Population Description

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/Group Title	TCZ IV Q4W 7 mg/kg	TCZ IV Q4W 6 mg/kg
Arm/Group Description	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).	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
Measure Participants	24	22
Baseline	57.80 (61.149)	39.46 (25.989)
Week 12	56.03 (84.988)	49.73 (81.718)
Week 16	97.57 (277.409)	43.04 (54.232)
Week 20	38.11 (21.147)	46.97 (61.454)
Week 24	111.00 (NA)

6. Secondary Outcome

Title	Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R)
Time Frame	Baseline; Weeks 12, 16, 20, 24

Outcome Measure Data

Analysis Population Description

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/Group Title	TCZ IV Q4W 7 mg/kg	TCZ IV Q4W 6 mg/kg
Arm/Group Description	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).	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
Measure Participants	24	22
Baseline	665.8 (153.81)	671.3 (152.69)
Week 12	680.8 (183.84)	670.9 (175.92)
Week 16	654.6 (173.26)	651.7 (136.95)
Week 20	663.8 (147.92)	690.0 (215.91)
Week 24	519.0 (NA)

7. Secondary Outcome

Title	Serum Concentration of C-Reactive Protein (CRP)
Time Frame	Baseline; Weeks 4, 8, 12, 16-24

Outcome Measure Data

Analysis Population Description

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/Group Title	TCZ IV Q4W 7 mg/kg	TCZ IV Q4W 6 mg/kg
Arm/Group Description	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).	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
Measure Participants	24	22
Baseline	0.615 (1.1645)	0.356 (0.2486)
Week 4	0.511 (0.7538)	0.591 (1.0646)
Week 8	0.426 (0.3687)	0.403 (0.3217)
Week 12	0.467 (0.5694)	0.359 (0.2585)
Week 16	0.344 (0.2795)	0.382 (0.3726)
Week 17	0.409 (0.2533)	0.409 (0.4521)
Week 18	0.374 (0.2994)	0.389 (0.3168)
Week 19	0.387 (0.2801)	0.388 (0.3348)
Week 20	0.340 (0.2172)	0.416 (0.2938)
Week 21	0.200 (0.0000)
Week 22	0.200 (0.0000)
Week 23	0.203 (0.0058)
Week 24	0.200 (0.0000)

8. Secondary Outcome

Title	Erythrocyte Sedimentation Rate (ESR)
Time Frame	Baseline; Weeks 4, 8, 12, 16-24

Outcome Measure Data

Analysis Population Description

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/Group Title	TCZ IV Q4W 7 mg/kg	TCZ IV Q4W 6 mg/kg
Arm/Group Description	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).	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
Measure Participants	24	22
Baseline	6.1 (6.72)	5.6 (5.01)
Week 4	4.7 (3.38)	5.6 (4.11)
Week 8	7.2 (12.25)	5.0 (3.13)
Week 12	5.9 (5.30)	6.5 (5.27)
Week 16	5.9 (4.56)	5.1 (4.32)
Week 17	5.2 (3.84)	5.0 (4.64)
Week 18	4.4 (3.99)	4.8 (3.01)
Week 19	4.3 (2.64)	5.0 (5.20)
Week 20	7.1 (6.19)	5.6 (5.04)
Week 21	4.5 (3.54)
Week 22	5.3 (3.79)
Week 23	4.0 (3.00)
Week 24	3.7 (1.53)

Adverse Events

Time Frame	Baseline - Day 151
Arm/Group Title	TCZ IV 7 mg/kg Q4W		TCZ IV 6 mg/kg Q4W
Arm/Group Description	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).		Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).
All Cause Mortality
	TCZ IV 7 mg/kg Q4W		TCZ IV 6 mg/kg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/22 (0%)
Serious Adverse Events
	TCZ IV 7 mg/kg Q4W		TCZ IV 6 mg/kg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/24 (12.5%)		1/22 (4.5%)
Ear and labyrinth disorders
Vertigo positional	0/24 (0%)	0	1/22 (4.5%)	1
Gastrointestinal disorders
Lower gastrointestinal haemorrhage	1/24 (4.2%)	1	0/22 (0%)	0
Infections and infestations
Pneumonia pneumococcal	1/24 (4.2%)	1	0/22 (0%)	0
Vascular disorders
Aortic aneurysm rupture	1/24 (4.2%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	TCZ IV 7 mg/kg Q4W		TCZ IV 6 mg/kg Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/24 (25%)		3/22 (13.6%)
Infections and infestations
Nasopharyngitis	3/24 (12.5%)	3	1/22 (4.5%)	1
Respiratory tract infection viral	1/24 (4.2%)	1	2/22 (9.1%)	2
Upper respiratory tract infection	2/24 (8.3%)	2	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.