Sarilumab Effect on the Pharmacokinetics of Simvastatin

A Multi-center, Open-label, 2-treatment, Single-sequence Clinical Study to Evaluate the Effects of a Single 200 mg Subcutaneous Injection of Sarilumab on the Pharmacokinetics of a Single 40 mg Oral Dose of Simvastatin, With Optional 1-year Extension of Open Label Treatment of Sarilumab, in Patients With Rheumatoid Arthritis

Primary Objective:

To evaluate the effect of a single 200 mg subcutaneous injection of sarilumab on the pharmacokinetics of simvastatin in patients with rheumatoid arthritis

Secondary Objective:

To describe the safety and efficacy (exploratory) of sarilumab

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: sarilumab SAR153191 (REGN88); Drug: simvastatin

Detailed Description

The duration of the entire study per patient completing both Parts A and B is expected to be approximately 58 weeks (not including Screening).

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Investigational Site Number 410002
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • Investigational Site Number 498001
• United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Investigational Site Number 840002
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Investigational Site Number 840003
  • Texas
    • Dallas, Texas, United States, 75235
      • Investigational Site Number 840001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Male or female, between 18 and 75 years of age, inclusive. Body weight between 50.0 and 120.0 kg, inclusive, if male, and between 40.0 and 110.0 kg, inclusive, if female.

Diagnosis of RA, according to the ACR/European League against Rheumatism (EULAR) 2010 Rheumatoid Arthritis Classification Criteria with ≥ 3 months disease duration, ACR Class I-III functional status, based on 1991 revised criteria (Appendix B, 5). Moderate-to-severely active RA, defined as:

o high sensitivity C-reactive protein (hs-CRP) ≥ 6 mg/L

Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for RA patients; however following lab values must be met:

• Hemoglobin >8.5 g/dL
• White blood cells >3000/mm3
• Neutrophils >2000/mm3
• Platelet count >150 000 cells/mm3

Exclusion criteria:

Prior or current significant concomitant illness(es) that, according to Investigator's judgment, would adversely affect the patient's participation in the study.

Women of childbearing potential not protected by highly-effective contraceptive method(s) of birth control (as defined in the informed consent form), and/or who are unwilling or unable to be tested for pregnancy.

Participation in any clinical research study that evaluated an investigational drug or therapy within 5 half-lives or 60 days of the Screening, whichever is longer.

Patients with active TB or a history of incompletely treated TB. History of chronic infection or active infection. History of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA.

A systemic hypersensitivity reaction, other than localized injection site reaction, to any biologic drug.

History or presence of drug or alcohol abuse. Prior or current interstitial lung disease diagnosed by high resolution computed tomography and/or lung biopsy with consistent findings on pulmonary function tests and corroborating clinical findings.

Prior or current history of malignancy, including lymphoproliferative diseases, other than adequately-treated carcinoma in-situ of the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the screening visit.

Uncontrolled diabetes mellitus, defined as glycosylated hemoglobin (HbA1c) ≥9% at the screening visit.

Current treatment with anti-TNF agents or other biologics. Current treatment with RA-directed biologic agents with non- TNF-α antagonist. Any contra-indications to simvastatin, according to the applicable labeling. Current treatment with a statin within 14 days before inclusion.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sarilumab SAR153191 (REGN88); Single dose of simvastatin before and after sarilumab administration	Drug: sarilumab SAR153191 (REGN88); Pharmaceutical form:Prefilled syringe of sarilumab solution Route of administration: Subcutaneous injection; Drug: simvastatin; Pharmaceutical form:Film-coated 20 mg Tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of PK parameters - area under curve from zero time until the last measurable concentration (AUClast) and AUC for simvastatin	Day 1 of Period 1 and Day 8 of Period 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of additional PK parameters for simvastatin	Day 1 of Period 1 and Day 8 of Period 2
Assessment of additional PK parameters for simvastatin acid	Day 1 of Period 1 and Day 8 of Period 2
Safety assessment of sarilumab up to 1 year )	From Day 1 of Period 1 up to a maximum of 1 year (week 58)

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Lee EB, Daskalakis N, Xu C, Paccaly A, Miller B, Fleischmann R, Bodrug I, Kivitz A. Disease-Drug Interaction of Sarilumab and Simvastatin in Patients with Rheumatoid Arthritis. Clin Pharmacokinet. 2017 Jun;56(6):607-615. doi: 10.1007/s40262-016-0462-8.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: December 2, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 23, 2013

Study Record Updates

• Last Update Posted (Estimate): April 7, 2016
• Last Update Submitted That Met QC Criteria: April 6, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: INT12684; U1111-1140-5082 (Other Identifier: UTN)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No