A Study to Evaluate the Efficacy and Safety of Rontalizumab in Patients With Moderately to Severely Active Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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This is a Phase II, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of rontalizumab compared with placebo in patients with moderately to severely active systemic lupus erythematosus (SLE).

Detailed Description
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The study will be conducted in 3 parts. Parts 1 and 2 of the study will include a double-blind treatment period of 24 weeks and a safety follow-up period of 48 weeks for participants who do not continue onto Part 3. Patients meeting the eligibility criteria for enrollment in Part 3, will enter Part 3 after completion of the Week 24 visit but prior to completion of the Week 72 visit. In Part 1, participants will be randomized in a 2:1 ratio (active drug:placebo) to receive either rontalizumab 750 mg or matching placebo intravenously every 4 weeks for 24 weeks. Part 2 was will be initiated upon the completion of recruitment for Part 1. In Part 2, participants will be randomized in a 2:1 ratio (active drug:placebo) to receive either rontalizumab 300 mg or matching placebo subcutaneously every 2 weeks for 24 weeks. After Week 24, patients will enter a 48-week safety follow-up period, or, after the open label extension became available via protocol amendment, will have the option of entering Part 3 of the study, if eligible. In Part 3, all participants will receive rontalizumab 750 mg intravenously every 4 weeks for 120 weeks (up to 144 weeks total).

Official Title
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A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rontalizumab (rhuMAb IFNalpha) in Patients With Moderately to Severely Active Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Placebo
* Drug: Rontalizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of SLE. Active disease at the time of screening. Agreement to use an effective form of contraception for the duration of the study. Exclusion Criteria: Acutely life- or organ-threatening manifestations of systemic lupus erythematosus (SLE) (eg, proliferative nephritis, unstable neuropsychiatric disease). Pregnancy or breastfeeding. History of severe allergic or anaphylactic reactions to monoclonal antibodies or intravenous (IV) immunoglobulin. Significant, uncontrolled medical disease in any organ system not related to SLE that in the investigator's opinion would preclude patient participation. Concomitant conditions that required systemic corticosteroid use within 1 year prior to screening. Use of topical, intraarticular, or inhaled corticosteroids is not exclusionary. History of cancer within 5 years of screening. Any current or recent (within 4 weeks of screening) signs or symptoms of infection, except for minor infections, fungal infections of the nail beds, or oral or vaginal candidiasis. History of severe systemic bacterial, fungal, viral, or parasitic infections (2 or more hospitalizations or 2 or more courses of IV antibiotics) within 6 months prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Part 1 - Placebo intravenously<br>Participants received placebo intravenously every 4 weeks for 24 weeks. | Drug: Placebo<br>* Placebo was supplied as a sterile liquid solution.<br>|
| Experimental: Part 1 - Rontalizumab 750 mg intravenously<br>Participants received rontalizumab 750 mg intravenously every 4 weeks for 24 weeks. | Drug: Rontalizumab<br>* Rontalizumab was supplied as a sterile liquid solution.<br>|
| Placebo Comparator: Part 2 - Placebo subcutaneously<br>Participants received placebo subcutaneously every 2 weeks for 24 weeks. | Drug: Placebo<br>* Placebo was supplied as a sterile liquid solution.<br>|
| Experimental: Part 2 - Rontalizumab 300 mg subcutaneously<br>Participants received rontalizumab 300 mg subcutaneously every 2 weeks for 24 weeks. | Drug: Rontalizumab<br>* Rontalizumab was supplied as a sterile liquid solution.<br>|
| Experimental: Part 3 - Rontalizumab 750 mg intravenously<br>Participants received rontalizumab 750 mg intravenously every 4 weeks for 120 weeks. | Drug: Rontalizumab<br>* Rontalizumab was supplied as a sterile liquid solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of responders at Week 24 |  | Until study discontinuation or up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-adjusted area under the curve (AUC) of the BILAG index global score |  | Until study discontinuation or up to 24 weeks | 
| Treatment failure status |  | Until study discontinuation or up to 24 weeks | 
| Time to treatment failure |  | Until study discontinuation or up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, rhuMAb IFNalpha