Exploratory Study of Changes in Disease Activity and Biomarkers With ABR-215757 in Patients With Mild Active Systemic Lupus Erythematosus (SLE)

NCT00997100 | Completed Phase 2

• 2 other identifiers: 095757042009-011245-55
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 4

Brief Summary

This is an exploratory open label single arm study to evaluate changes in disease activity and biomarkers in patients with mild active SLE, during treatment with ABR-215757 given as add-on to standard therapy. To be eligible for the study SLE patients should present with symptoms from skin, mouth and/or joints. After a screening period of one week patients will be treated with ABR-215757 for 12 weeks. The initial dose of ABR-215757 will be 1.5 mg/day. There will be an option to increase the dose to 3.0 mg/day following 28 days of treatment. Follow-up visits will take place 4 weeks and 8 weeks after last day of treatment. Disease activity during treatment will be studied using the Systemic Lupus Erythematosus disease Activity Index (SLEDAI-2K) as well as organ system specific disease activity indexes (CLASI for skin involvement and number of swollen/tender joints using 28- and 66/68-joint counts). At specified time points during the study, blood samples and biopsies will be collected for analysis of established and exploratory biomarkers of SLE. Concomitant SLE treatment allowed include: prednisolone or equivalent at a dose of ≤15 mg/day, hydroxychloroquine, azathioprine, methotrexate and mycophenolate mofetil, all at stable doses from specified timepoints prior to the study and throughout the study.

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic Lupus Erythematosus (SLE); ABR-215757; Change in Biomarkers

Outcome Measures

Primary Outcomes (1)

• Changes in disease activity and biomarkers in patients with mild active SLE treated with ABR-215757

  Patients will be treated for 12 weeks with ABR-215757. During treatment there will be scheduled visits on days 14, 28, 56 and 84. Follow-up visits will take place 29 days and 57 days after last dose of ABR-215757

Secondary Outcomes (1)

• To assess the safety and tolerability of ABR-215757 in SLE patients with mild active disease. To assess plasma levels of ABR-215757 during the study

  Patients will be treated for 12 weeks with ABR-215757. During treatment there will be scheduled visits on days 14, 28, 56 and 84. Follow-up visits will take place 29 days and 57 days after last dose of ABR-215757

Study Arms (1)

ABR-215757

OTHER

Drug: paquinimod (ABR-215757)

Interventions

paquinimod (ABR-215757) DRUG

The initial daily dose of ABR-215757 is changed to 1.5 mg/day. There will be an option to increase the dose to 3.0 mg/day following 28 days of treatment

Also known as: ABR-215757, paquinimod

ABR-215757

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years at the time of signing the informed consent form
• Fulfil at least 4 criteria for SLE as defined by the American College of Rheumatology (ACR)
• Present with active SLE disease with at least one of the following symptoms:
• i) Arthritis - \> 2 joints with pain and signs of inflammation (i.e. tenderness, swelling, or effusion) ii) Inflammatory-type skin rash iii) Oral ulcers
• Laboratory values as follows
• Hemoglobin ≥ 100 g/L
• Absolute neutrophil count ≥ 1.0 x 109/L
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• AST (SGOT) / ALT (SGPT) ≤ 2.5 x ULN
• Ability to take and retain oral medication
• Ability to sign and date a written informed consent prior to entering the study
• Willingness and ability to comply with the protocol for the duration of the study

You may not qualify if:

• Active severe SLE flare with central nervous system (CNS) manifestations, active renal lupus, systemic vasculitis, active pericarditis, active pleuritis, active peritonitis or other SLE manifestations requiring treatment not allowed by the study protocol.
• Severe renal impairment (estimated or measured GFR \<50%)
• Oral treatment with corticosteroids (\>15 mg/day prednisolone or equivalent) or changes in corticosteroid dosing within 30 days prior to the first dose of study medication. This also includes intraarticular steroid injections or topical treatment for SLE symptoms. Inhaled or topical steroids may be given for reasons other than SLE disease activity (such as asthma, contact dermatitis) as clinically indicated.
• Intravenous corticosteroids within 3 months prior to the first dose of study medication.
• Intravenous cyclophosphamide within 6 months prior to the first dose of study medication.
• Treatment with anti-rheumatic/immunosuppressive drugs within 3 months prior to first dose of study medication, other than the following medications at stable doses: methotrexate (≤25 mg/week), azathioprine (≤2.5 mg/kg/day), hydroxychloroquine and mycophenolate mofetil (≤3000 mg/day).
• B-cell depletion therapy (such as treatment with Rituximab) within 12 months prior to the first dose of study medication.
• Potent inhibitors or inducers of CYP3A4 intravenously or orally within 14 days prior to first dose of study medication.
• History of myocardial infarction or current uncontrolled angina, severe uncontrolled ventricular arrhythmias, symptomatic congestive heart failure, unstable angina pectoris, or electrocardiographic evidence of acute ischemia.
• Marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval \>450 milliseconds
• History of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome)
• Treatment with concomitant medications that prolong the QT interval.
• History of, or current, ischemic CNS disease.
• Current malignancy. A 5-year cancer-free period is required with the exception of skin basal or squamous cell carcinoma or cervical cancer in situ that has been excised.
• Current severe infection

Sponsors & Collaborators

• Active Biotech AB: lead

Study Sites (4)

Soren Jacobsen

Copenhagen, Copenhagen, 2100, Denmark

Location

Dept of Rheumatology, University Hospital in Lund

Lund, Lund, 220 07, Sweden

Location

Iva Gunnarsson M.D.

Stockholm, Stockholm County, 171 76, Sweden

Location

Lars Rönnblom M.D.

Uppsala, Uppsala County, 751 85, Sweden

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

paquinimod

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Marie Wallén Öhman, Ph.D.

  Active Biotech AB

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2009
• First Posted: October 19, 2009
• Study Start: August 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: June 25, 2015

Record last verified: 2015-06

Locations

SE (3); DK (1)