Clinical trial NCT02404558: Single-dose Study to Describe the Safety of Sarilumab and Tocilizumab in Patients With Rheumatoid Arthritis
Official title: An Open-label, Randomized, Parallel Group, Single-dose Study to Describe the Safety of IL-6 Receptor Blockade With Sarilumab or Tocilizumab Monotherapy in Japanese Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2015-03-31
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To describe the safety and tolerability, including laboratory abnormalities following a single dose of sarilumab or tocilizumab administered subcutaneously (SC) as monotherapy in Japanese patients with rheumatoid arthritis (RA).

Secondary Objectives:

To describe the laboratory abnormalities (absolute neutrophil count \[ANC\], platelet counts, total cholesterol, high-density lipoprotein \[HDL\] cholesterol, low-density lipoprotein \[LDL\] cholesterol, and liver function tests \[LFTs\]) following a single dose of sarilumab or tocilizumab administered SC as monotherapy in Japanese patients with RA.

To describe the pharmacokinetics (PK) of sarilumab and tocilizumab.

Detailed description: Total study duration (per patient) is expected to be up to 71 days including screening (3 to 28 days before dosing).

Eligibility criteria: Inclusion criteria:

* Patients with rheumatoid arthritis (RA) as defined by the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2010
* Rheumatoid Arthritis Classification Criteria.
* ACR Class I-III functional status, based on the 1991 revised criteria.

Exclusion criteria:

* Patients less than 20 years of age.
* Prior treatment with any biologic anti-interleukin-6 (anti-IL-6) or interleukin-6 receptor (IL-6R) antagonist.
* Any parenteral or intraarticular glucocorticoid injection within 4 weeks prior to randomization.
* Treatment with prednisone higher than 10 mg or equivalent per day, or change in dosage within 4 weeks prior to randomization.
* Treatment with disease-modifying antirheumatic drugs (DMARDs), immunosuppressive agents, tumor necrosis factor (TNF) antagonists or any other RA-directed biologic agents within a certain amount of time prior to randomization.
* Participation in any clinical research study that evaluated an investigational drug or therapy within 5 half-lives or 60 days of the screening visit, whichever is longer.
* Active or suspected tuberculosis (TB) or at high risk of contracting TB.
* Fever, or chronic, persistent, or recurring infection(s) requiring active treatment.
* The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Percentage of patients with adverse events
timeFrame: 6 weeks
measure: Percentage of patients with potentially clinically significant laboratory abnormalities
timeFrame: 6 weeks
measure: Change from baseline in laboratory parameters (hematology and biochemistry)
timeFrame: Baseline, Day 15
measure: Weighted average of change from baseline in laboratory parameters (hematology and biochemistry)
timeFrame: Baseline, Day 15
Secondary outcomes:
measure: Assessment of PK parameter: maximum concentration (Cmax)
timeFrame: Day 1 to Day 43
measure: Assessment of PK parameter: time to Cmax (tmax)
timeFrame: Day 1 to Day 43
measure: Assessment of PK parameter: area under the curve from zero time until the last measurable concentration (AUClast)
timeFrame: Day 1 to Day 43
measure: Change from baseline in laboratory parameters (hematology and biochemistry)
timeFrame: Baseline, Day 29 and Day 43
measure: Weighted average of change from baseline in laboratory parameters (hematology and biochemistry)
timeFrame: Baseline, Day 29 and Day 43
Other outcomes:
Locations:
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 392001
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 392002
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 392003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Kovalenko P, Paccaly A, Boyapati A, Xu C, St John G, Nivens MC, Davis JD, Rippley R, DiCioccio AT. Population Pharmacodynamic Model of Neutrophil Margination and Tolerance to Describe Effect of Sarilumab on Absolute Neutrophil Count in Patients with Rheumatoid Arthritis. CPT Pharmacometrics Syst Pharmacol. 2020 Jul;9(7):405-416. doi: 10.1002/psp4.12534. Epub 2020 Jun 20.