A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial of Epratuzumab in Patients with Acute Severe SLE Flares Excluding the Renal or Neurological Systems - Phase III Study of Epratuzumab in Severe Acute SLE Flares

• Register: EUCTR
• Last refreshed on: 24 April 2012
• Main ID: EUCTR2005-000705-59-GB
• Date of registration: 19/04/2005
• Prospective Registration: Yes
• Primary sponsor: Immunomedics, Inc.
• Public title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial of Epratuzumab in Patients with Acute Severe SLE Flares Excluding the Renal or Neurological Systems - Phase III Study of Epratuzumab in Severe Acute SLE Flares
• Scientific title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial of Epratuzumab in Patients with Acute Severe SLE Flares Excluding the Renal or Neurological Systems - Phase III Study of Epratuzumab in Severe Acute SLE Flares
• Date of first enrolment: 07/06/2005
• Target sample size: 510
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-000705-59
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany, Hungary, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
-Male or female, 18 years and older;
-Signed written informed consent obtained prior to study entry;
-Has SLE by American College of Rheumatology revised criteria (meets at least 4 criteria);
-Has a positive ANA at study entry;
-Has new onset of BILAG index A level activity in at least one body/organ system outside the renal and CNS systems;
-If initiated corticosteroids for the current flare, any increase of more than 10 - 15 mg/day prednisone (or equivalent) must occur no more than 14 days prior to the anticipated date to begin first infusion of study drug;
-If on immunosuppressives, must have been receiving immunosuppressives for at least 8 weeks, with a stable dose regimen for at least 4 weeks prior to study entry; and
-If on antimalarials, must have been receiving antimalarials for at least 12 weeks, with a stable dose regimen for at least 4 weeks prior to study entry.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test;
-Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control during and for a period of 6 months after the completion of the study;
-Active severe CNS disease;
-Active severe renal disease;
-Treatment with Lymphostat B, or CTLA4-Ig within 6 months, or with rituximab or other anti-B-cell ABs within 12 months;
-Allergy to murine or human ABs;
-Experimental therapy or any therapy with human or murine ABs within 3 months;
Cyclophosphamide, cyclosporin, intravenous, joint or IM injections of corticosteroids exceeding 120 mg methylprednisolone, 60 mg triamcinolone, or equivalent; IV immunoglobulins, or any IMPs within 4 weeks;
-Thrombosis, spontaneous or induced abortion, stillbirth or live birth, within 4 weeks;
-Patients with antiphospholipid ABs AND a history of thromboembolic events;
-On oral anticoagulants within 4 weeks;
-History of malignancy (except basal or squamous cell carcinoma, cervical CIS);
-Active infection receiving antibiotics within 7 days of screening or infection requiring hospitalization or herpes zoster treatment within 4 weeks; long-term infectious diseases (tuberculosis, fungal infections) active within 2 years;
-Known HIV, hepatitis B or C infection, or other immunosuppressive states;
-Live vaccine within 4 weeks;
-Hematological abnormalities not attributed to lupus;
-Liver transaminases or alkaline phosphatase > 3X upper limit of normal and not attributed to SLE;
-Serum creatinine > 2.5 mg/dL or clinically significant increases within 4 weeks, or proteinuria > 3.5 mg/day; and
-Substance abuse or other concurrent medical conditions that, in the investigator's opinion, could confound study interpretation or affect the patient's ability to tolerate or complete the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus
Classification code 10042945

Intervention(s)

Product Name: Epratuzumab
Product Code: IMMU-103
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 205923-57-5
Current Sponsor code: IMMU-103
Other descriptive name: hLL2 (trivial name or chemical description)
Concentration unit: % (W/V) percent weight/volume
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: The primary study objective is to demonstrate that epratuzumab is effective in the treatment of acute lupus flare.

Primary end point(s): The primary efficacy endpoint evaluated at 24 weeks is a patient response variable with three ordered categories; complete response (CR), partial response (PR) and non-response (NR).
In order to be given a response status of CR or PR, a patient must meet two minimum conditions: (i) not be considered a treatment failure and (ii) not have any BILAG Index A score in any body/organ system at any post-treatment evaluation time-point from weeks 4 to 24. In addition, if the patient also satisfies the protocol-defined steroid-tapering criterion at 24 weeks and does not have any BILAG Index B score, in any body/organ system at any post-treatment evaluation time-point from weeks 4 to 24, the patient will be assigned a CR status. Otherwise, the patient will be assigned a PR status provided the two minimum conditions are satisfied.
Requirements for CR and PR are summarized in the protocol (page 22).
A patient who fails to meet the two minimum conditions will be assigned a NR status.

Secondary Objective: -To evaluate the effectiveness of epratuzumab in treating severe disease activity (acute flare) and in maintaining disease control
-To evaluate the ability of epratuzumab to reduce the use of corticosteroids and other lupus medications.
-To demonstrate the safety of epratuzumab in patients with SLE.
-To assess the effect of adding epratuzumab to standard care on the quality of life of patients with SLE.
Supplemental endpoints:
-Time-to-reflare (new/recurrent BILAG A or B) among patients with no BILAG index B (or A) scores in any body/organ system at 4 weeks as well as the proportion of patients with these reflares.
-Proportion of patients able to maintain successful steroid-tapering from week 24 to 48.

Secondary ID(s)

IMMU-103-03