Clinical trial NCT02321709: Multiple Ascending Dose Study To Assess The Safety Profile 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 Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2014-12-22
Enrollment: 21
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:

To assess the tolerability and safety of SAR113244 in male and female lupus patients after every 4 (Q4) weeks repeated ascending subcutaneous doses of SAR113244.

Secondary Objectives:

To assess in male and female lupus patients:

* The pharmacokinetics of SAR113244.
* The pharmacodynamics of SAR113244 for the following disease-related 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 (SRI) (if applicable), Lupus-quality of life (QoL) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, anti-double stranded deoxyribonucleic acid antibody (anti-dsDNA Ab) and anti-nuclear antibody levels (ANA) and plasma complement levels (C3, C4), erythrocyte sedimentation (SED) rate and C-reactive protein.
  * Peripheral blood B and T cells subsets.

Detailed description: The total duration of screening to end of study per subject is 20 weeks with post-study observation on Day 226 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 systemic lupus erythematosus (SLE) by American College Rheumatology criteria.
* Autoantibody-posititve.
* On active and stable SLE disease.

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, whichever 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 postitive 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: Number of participants with adverse events and treatment-emergent adverse events
timeFrame: Up to 16 weeks after inclusion
measure: Change in physical examination, body weight, vital signs and laboratory parameters
timeFrame: Up to 16 weeks after inclusion
measure: Safety and tolerability (erythema, swelling, degree of itching, and present pain intensity at injection site by measuring diameter and qualitative assessment)
timeFrame: Up to 16 weeks after inclusion
Secondary outcomes:
measure: Assessment of pharmacokinetic parameter - maximum concentration (Cmax)
timeFrame: Up to D113 after inclusion
measure: Assessment of pharmacokinetic parameter - time of maximum concentration (Tmax)
timeFrame: Up to D113 after inclusion
measure: Assessment of pharmacokinetic parameter - area under curve 0-4 weeks (AUC0-4w)
timeFrame: Up to D113 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 D113 after inclusion
measure: Assessment of pharmacokinetic parameter - lowest concentration of drug before the next dose (Ctrough)
timeFrame: Up to D113 after inclusion
measure: Assessment of pharmacokinetic parameter - apparent total body clearance (CLss/F)
timeFrame: Up to D113 after inclusion
measure: Assessment of pharmacokinetic parameter - absorption-dependent apparent volume of distribution at steady state (Vss/F)
timeFrame: Up to D113 after inclusion
measure: Number of participants with anti-SAR113244 antibody titers
timeFrame: Up to D226 after inclusion
measure: Pharmacodynamic parameter changes
timeFrame: Up to D113 after inclusion
measure: Pharmacodynamic parameters: peripheral blood B and T cells subsets
timeFrame: Up to D85 after inclusion
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Investigational Site Number 276001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: