Phase Ib Study of SC Milatuzumab in SLE

Study Overview
=================
Brief Summary
-----------------
Milatuzumab will be given subcutaneously at different dose levels once (depending on the dose level) for 4 weeks to determine if milatuzumab helps to control lupus (SLE).

Detailed Description
-----------------
Milatuzumab or placebo will be given subcutaneously once weekly for 4 weeks to determine if milatuzumab helps to control lupus (SLE). The treatment portion of the study lasts 4 weeks. Then patients are followed for disease activity for at least 12 weeks. If patients respond to the study drug, they may be eligible for one course of retreatment, again followed by 12 weeks of follow-up. Patients who showed a response will continue to be followed at timepoints up to one year after treatment to assess how long the response lasts.

Official Title
-----------------
A Phase Ib Study of Milatuzumab Administered Subcutaneously in Patients With Active Systemic Lupus Erythematosus (SLE)

Conditions
-----------------
Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic, Lupus Vasculitis, Central Nervous System, Lupus Nephritis

Intervention / Treatment
-----------------
* Drug: milatuzumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female ≥ 18 years old Signed written informed consent before study entry Diagnosis of SLE by American College of Rheumatology revised criteria (meets ≥ 4 criteria) Positive ANA (titer ≥ 1:80) at study entry At least 1 BILAG A or 2 BILAG B scores in any organ/body system and ≥ 6 SELENA-SLEDAI score Receiving at least 5.0 mg/day oral prednisone (or equivalent) at stable doses for at least 4 weeks prior to study entry If receiving immunosuppressives or antimalarial agents, at stable doses for at least 4 weeks prior to study entry Exclusion Criteria: Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test. Women of childbearing potential and fertile men not practicing or unwilling to practice birth control during the study Rituximab, belimumab, other prior antibody, investigational or experimental therapy within 6 months Allergic to murine, chimeric, humanized or human antibodies Hematologic abnormalities not attributed to lupus: hemoglobin < 8.0 mg/dL, WBC < 2000/L, ANC < 1500/L, platelets < 50,000/L, AST, ALT or alkaline phosphatase > 3 times upper limit of normal and not attributed to lupus Serum creatinine > 2.5 mg/dL, proteinuria > 3.5 g/day Received live vaccine within 4 weeks Thrombosis, spontaneous or induced abortion, stillbirth or live birth within 4 weeks Antiphospholipid antibodies AND a history of thromboembolic events On oral anticoagulants (not including NSAIDs) within 4 weeks Active infection with antibiotics within 7 days Infection requiring hospitalization or herpes zoster treatment within 4 weeks Long-term infectious diseases (tuberculosis, fungal infections) active within 2 years Malignancy (except squamous or basal cell carcinoma, cervical CIS) within 3 years (unless approved by the medical monitor) History of recurrent abortions (2 or more) Known HIV, hepatitis B or C, other immunosuppressive states Other concurrent medical conditions that, in the investigator's opinion, could affect the patient's ability to tolerate or complete the study will not be eligible for the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Milatuzumab SC 250 mg<br>Milatuzumab 250 mg will be administered subcutaneously once weekly for 4 weeks. | Drug: milatuzumab<br>* Milatuzumab has been used in clinical trials for multiple myeloma, non-Hodgkin's lymphoma and leukemia in the intravenous dosing form. In this study, milatuzumab is being given subcutaneously in patients with lupus.<br>* Other names: Milatuzumab is a Cd74 targeted humanized monoclonal antibody.;|
| Experimental: Milatuzumab 150 mg SC<br>Milatuzumab 150 mg will be administered subcutaneously once weekly for 4 weeks. | Drug: milatuzumab<br>* Milatuzumab has been used in clinical trials for multiple myeloma, non-Hodgkin's lymphoma and leukemia in the intravenous dosing form. In this study, milatuzumab is being given subcutaneously in patients with lupus.<br>* Other names: Milatuzumab is a Cd74 targeted humanized monoclonal antibody.;|
| Placebo Comparator: Placebo SC<br>Placebo will be administered subcutaneously once weekly for 4 weeks. | Drug: Placebo<br>* Placebo will be administered subcutaneously once weekly for 4 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Will be assessed using laboratory and clinical data comparing baseline lab results and clinical condition to the lab results and clinical condition/adverse events during treatment and follow-up timepoints up to 2 years. | up to 2 years | 
| Obtain preliminary evidence of efficacy for patients with active disease. | Will be assessed using the BILAG scoring model for lupus disease activity and symptoms by comparing baseline BILAG measurements against the BILAG measurements obtained during treatment and during follow-up for up to 2 years. | up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
systemic lupus erythematoses, lupus, SLE