Pharmacodynamics Assessment Study After Single Subcutaneous Dose Of SAR113244 Versus Placebo In Lupus Male And Female Patients

A Randomized, Double-blind, Placebo-controlled Study Of Safety, Tolerability, And Pharmacokinetics Of Repeated Ascending Subcutaneous Doses Of SAR113244 And Pharmacodynamics Of Single Dose Of SAR113244 In Male And Female Lupus Patient

Primary Objective:

Assess in systemic lupus erythematosus (SLE) patients the effect of SAR113244 on B-cell subsets compared to placebo.

Secondary Objectives:

Assess in male and female lupus patients after SC single dose of SAR113244 the tolerability and safety of SAR113244.

Assess in male and female lupus patients:

• The pharmacokinetics of SAR113244.

• The pharmacodynamics of SAR113244 for the following disease parameters:

  • Safety of Estrogens in Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score, British Isles Lupus Assessment Group (BILAG) score (if applicable), BILAG-Based Composite Lupus Assessment (BICLA) (if applicable), systemic lupus erythematosus responder index (if applicable), Lupus-quality of life and Functional Assessment of Chronic Illness Therapy-Fatigue, anti-double stranded deoxyribonucleic acid antibody and anti-nuclear antibody levels and plasma complement levels (C3, C4), erythrocyte sedimentation rate and C-reactive protein.
  • Peripheral blood B and T cell subsets.

Study Overview

• Status: Withdrawn
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: SAR113244; Drug: placebo

Detailed Description

The total duration of screening to end of study per subject is 16 weeks with post-study observation on Day 198 for anti-drug antibody assessment (for patients with positive anti-drug antibody at end of study only).

• Study Type: Interventional
• Phase: Phase 1

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 patients, between 18 and 75 years of age, inclusive.
• Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria.
• Autoantibody-positive.
• On active and stable SLE disease.
• B cell subsets expressed as percentage of total B cells above normal.

Exclusion criteria:

• Pregnant and nursing.
• Have received treatment with investigational drugs in the 4 months prior to the screening or 5 half-lives of the drug, which ever is longer.
• Have received intravenous or oral cyclophosphamide within 180 days of Day 0.
• Severe active lupus nephritis or chronic renal insufficiency.
• Active or chronic, severe neuropsychiatric lupus.
• Acute, recent (within 4 weeks of screening), chronic or frequently recurring infection(s), except minor infection.
• Have current drug or alcohol abuse or dependence.
• Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.

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: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR113244; Single subcutaneous dose of SAR113244	Drug: SAR113244; Pharmaceutical form:solution for injection Route of administration: subcutaneous
Placebo Comparator: Placebo; Single subcutaneous dose of placebo	Drug: placebo; Pharmaceutical form:solution for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage decrease in B cell subsets (expressed as percentages of total B-cells) from baseline	Up to Day 57 after inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of pharmacokinetic parameter - maximum concentration (Cmax)	Up to Day 198 after inclusion
Assessment of pharmacokinetic parameter - time of maximum concentration (Tmax)	Up to D198 after inclusion
Assessment of pharmacokinetic parameter - area under curve from zero to infinity (AUCinf)	Up to Day 198 after inclusion
Assessment of pharmacokinetic parameter - time of the last point with quantifiable concentration (tlast) and terminal elimination half-life (t1/2z)	Up to Day 85 after inclusion
Assessment of pharmacokinetic parameter-apparent oral clearance (CL/F)	Up to Day 85 after inclusion
Assessment of pharmacokinetic parameter- absorption-dependent apparent volume of distribution at steady state (Vss/F)	Up to Day 85 after inclusion
Number of participants with anti-SAR113244 antibody titers	Up to Day 198 after inclusion
Number of participants with adverse events and treatment-emergent adverse events, including those that deviated from baseline values of hematology, biochemistry, coagulation and urine	Up to Day 198 after inclusion
Number of participants with injection site reactions	Up to Day 85 after inclusion
Number of participants with abnormalities and changes in laboratory parameters	Up to Day 85 after inclusion
Assessment of pharmacodynamics - clinical and/or lupus-related scores	Up to Day 85 after inclusion
Assessment of pharmacodynamics - blood/urine parameters	Up to Day 85 after inclusion
Pharmacodynamic parameters: peripheral blood B and T cells subsets	Up to Day 85 after inclusion

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Anticipated): May 1, 2017
• Study Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: December 5, 2014
• First Submitted That Met QC Criteria: January 2, 2015
• First Posted (Estimate): January 6, 2015

Study Record Updates

• Last Update Posted (Estimate): June 3, 2016
• Last Update Submitted That Met QC Criteria: June 2, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: PDY14076; 2014-001690-13 (EudraCT Number); U1111-1154-6184 (Other Identifier: UTN)