A Study to Evaluate the Pharmacokinetics, Pharmacodynamic... | NCT03923738

ID	Type	Description	Link
2018-004718-17	EudraCT Number

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
TCZ IV Q4W	Experimental	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Tocilizumab	Drug	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.

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	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

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Universitätsspital Basel; Rheumatologie		Basel		4031	Switzerland
Inselspital Bern; Rheumatologie; Klinische Immunologie und Allergologie

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35659282	Derived	Schmitt C, Brockwell L, Giraudon M, Zucchetto M, Christ L, Bannert B, Daikeler T, Villiger PM. Intravenous tocilizumab for the treatment of giant cell arteritis: a phase Ib dose-ranging pharmacokinetic bridging study. Arthritis Res Ther. 2022 Jun 4;24(1):133. doi: 10.1186/s13075-022-02815-9.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 6, 2019	Nov 4, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG00024

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00067.9± 8.1

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00015
Male	BG0009

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000
Not Hispanic or Latino	BG00024

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000
Asian	BG0001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Serum Concentration (Cmax) of TCZ

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.

Posted

Median

Full Range

ug/mL

Baseline; Weeks 4, 8, 12, 16-24

ID	Title	Description
OG000	TCZ IV Q4W 7 mg/kg	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).
OG001	TCZ IV Q4W 6 mg/kg	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).

Units	Counts
Participants	OG00021 OG00122

Title

Denominators

Categories

Title	Measurements
	OG000197(118 to 352) OG001178(115 to 320)

Primary

Trough Serum Concentration (Ctrough) of TCZ at Steady State

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.

Posted

Median

Full Range

ug/mL

Baseline; Weeks 4, 8, 12, 16-24

ID	Title	Description
OG000	TCZ IV Q4W 7 mg/kg	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).
OG001	TCZ IV Q4W 6 mg/kg	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).

Units	Counts
Participants	OG000

Primary

Area Under the Concentration-Time Curve Over the Dosing Interval of 4 Weeks (AUC4weeks) of TCZ at Steady State

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.

Posted

Median

Full Range

day*ug/mL

Baseline; Weeks 4, 8, 12, 16-24

ID	Title	Description
OG000	TCZ IV Q4W 7 mg/kg	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).
OG001	TCZ IV Q4W 6 mg/kg	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).

Units	Counts
Participants	OG000

Primary

Percentage of Participants With Adverse Events

Posted

Number

Percentage of Participants

Baseline - Day 151

ID	Title	Description
OG000	TCZ IV Q4W 7 mg/kg	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).
OG001	TCZ IV Q4W 6 mg/kg	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).

Units	Counts
Participants	OG000

Secondary

Serum Concentration of Interleukin-6 (IL-6)

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.

Posted

Mean

Standard Deviation

pg/mL

Baseline; Weeks 12, 16, 20, 24

ID	Title	Description
OG000	TCZ IV Q4W 7 mg/kg	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).
OG001	TCZ IV Q4W 6 mg/kg	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).

Units	Counts
Participants	OG000

Secondary

Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R)

Posted

Mean

Standard Deviation

ng/mL

Baseline; Weeks 12, 16, 20, 24

ID	Title	Description
OG000	TCZ IV Q4W 7 mg/kg	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).
OG001	TCZ IV Q4W 6 mg/kg	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).

Units	Counts
Participants	OG000

Secondary

Serum Concentration of C-Reactive Protein (CRP)

Posted

Mean

Standard Deviation

mg/L

Baseline; Weeks 4, 8, 12, 16-24

ID	Title	Description
OG000	TCZ IV Q4W 7 mg/kg	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).
OG001	TCZ IV Q4W 6 mg/kg	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).

Units	Counts
Participants	OG000

Secondary

Erythrocyte Sedimentation Rate (ESR)

Posted

Mean

Standard Deviation

mm/h

Baseline; Weeks 4, 8, 12, 16-24

ID	Title	Description
OG000	TCZ IV Q4W 7 mg/kg	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).
OG001	TCZ IV Q4W 6 mg/kg	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	TCZ IV 7 mg/kg Q4W	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).	0	24	3	24	6	24
EG001	TCZ IV 6 mg/kg Q4W	Participants that completed Period 1 and were in remission received 5 or 6 consecutive doses of 6 mg/kg IV TCZ Q4W (Period 2).	0	22	1	22	3	22

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo positional	Ear and labyrinth disorders	MedDRA 23.1	Non-systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected22 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.1	Non-systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected22 at risk
Pneumonia pneumococcal	Infections and infestations	MedDRA 23.1	Non-systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected22 at risk
Aortic aneurysm rupture	Vascular disorders	MedDRA 23.1	Non-systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected22 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 23.1	Non-systematic Assessment	EG0003 events3 affected24 at risk EG0011 events1 affected22 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 23.1	Non-systematic Assessment	EG0001 events1 affected24 at risk EG0012 events2 affected22 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23.1	Non-systematic Assessment	EG0002 events2 affected24 at risk EG0010 events0 affected22 at risk

Ancestor Terms

ID	Term
D020293	Vasculitis, Central Nervous System
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D002561	Cerebrovascular Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D001167	Arteritis
D014657	Vasculitis
D017445	Skin Diseases, Vascular
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases