Clinical trial NCT02331810: Pharmacodynamics Assessment Study After Single Subcutaneous Dose Of SAR113244 Versus Placebo In Lupus Male And Female Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2015-01-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage decrease in B cell subsets (expressed as percentages of total B-cells) from baseline
timeFrame: Up to Day 57 after inclusion
Secondary outcomes:
measure: Assessment of pharmacokinetic parameter - maximum concentration (Cmax)
timeFrame: Up to Day 198 after inclusion
measure: Assessment of pharmacokinetic parameter - time of maximum concentration (Tmax)
timeFrame: Up to D198 after inclusion
measure: Assessment of pharmacokinetic parameter - area under curve from zero to infinity (AUCinf)
timeFrame: Up to Day 198 after inclusion
measure: Assessment of pharmacokinetic parameter - time of the last point with quantifiable concentration (tlast) and terminal elimination half-life (t1/2z)
timeFrame: Up to Day 85 after inclusion
measure: Assessment of pharmacokinetic parameter-apparent oral clearance (CL/F)
timeFrame: Up to Day 85 after inclusion
measure: Assessment of pharmacokinetic parameter- absorption-dependent apparent volume of distribution at steady state (Vss/F)
timeFrame: Up to Day 85 after inclusion
measure: Number of participants with anti-SAR113244 antibody titers
timeFrame: Up to Day 198 after inclusion
measure: Number of participants with adverse events and treatment-emergent adverse events, including those that deviated from baseline values of hematology, biochemistry, coagulation and urine
timeFrame: Up to Day 198 after inclusion
measure: Number of participants with injection site reactions
timeFrame: Up to Day 85 after inclusion
measure: Number of participants with abnormalities and changes in laboratory parameters
timeFrame: Up to Day 85 after inclusion
measure: Assessment of pharmacodynamics - clinical and/or lupus-related scores
timeFrame: Up to Day 85 after inclusion
measure: Assessment of pharmacodynamics - blood/urine parameters
timeFrame: Up to Day 85 after inclusion
measure: Pharmacodynamic parameters: peripheral blood B and T cells subsets
timeFrame: Up to Day 85 after inclusion
Other outcomes:
Locations:
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: