Proof-of-Concept Study With BT063 in Subjects With Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of repeated intravenous infusions of the study drug BT063 in patients with Systemic Lupus Erythematosus (SLE) compared with people who receive a placebo.

Detailed Description
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Study 990 is a Phase IIa, proof-of-concept study of BT063 in subjects with SLE. This study is divided into 2 parts. After Part I an interim analysis will be performed. Each Part will enrol 18 subjects. Subjects will be randomly assigned to receive BT063 or Placebo 8 times over 12 weeks and will be followed for 4 months after their last dose.

Official Title
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A Prospective, Double-blind, Randomized, Placebo-controlled, Repeated Dose, Multicentre Phase IIa Proof-of-Concept Study With BT063 in Subjects With Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: BT063
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible male and female subjects, Age ≥ 18 and ≤ 75 years with Body mass index ≥ 18 and ≤ 35 kg/m2 at screening visit Diagnosed SLE (defined by ≥ 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE) for at least 3 months before screening Moderate to severe SLE disease activity demonstrated by SLEDAI-2K total score ≥ 6, including skin and joint involvement CLASI Activity score ≥ 5 or at least 5 of 66/68 joints with pain and signs of inflammation Positive anti-nuclear antibodies (ANA) test at screening No change in concomitant medication for SLE activity maintenance and symptom control regarding type of medication and dose level for at least 8 weeks prior to baseline (for steroids and NSAIDs/pain medication 2 weeks) Normal electrocardiogram (ECG) Exclusion Criteria: Active, severe neuropsychiatric SLE defined as any neuropsychiatric element scoring BILAG level A disease or lupus nephritis Diagnosed psoriasis Presence or history of malignancy within the previous 5 years Systemic antibiotic treatment within 2 weeks before baseline visit A positive diagnosis for viral hepatitis B or hepatitis C or Human immunodeficiency virus (HIV) or tested positive for tuberculosis as assessed or recent infection with Herpes Zoster or Herpes Simplex (Type 1 and Type 2), Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection or reactivation at screening Clinically significant hematologic abnormalities attributed to SLE: Haemoglobin < 8 g/dL; Platelets < 50 E9/L; Leucocytes < 2.0 E9/L Active or history of inflammatory bowel disease (including active or history of colitis) Received the following medications: - Rituximab within the last 48 weeks before screening - Belimumab within the last 12 weeks before screening - IV immunoglobulin (Ig) within the last 12 weeks before screening - Intramuscular (IM) or intra-articular glucocorticosteroids within the last 4 weeks before screening - IV cyclophosphamide within the last 6 months before screening - IV glucocorticosteroids (pulse therapy) within the last 6 months before screening Pregnant or nursing women or women who intend to become pregnant Known intolerance to immunoglobulins or comparable substances (e.g., significant vaccination reaction) Known intolerance to proteins of human origin History of clinically significant drug or alcohol abuse within the last 12 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BT063<br>50 mg BT063 administered by intravenous (IV) infusion 8 times | Biological: BT063<br>* Repeated IV infusions over 12 weeks (at weeks 0, 1, 2, 4, 6, 8, 10, 12)<br>|
| Placebo Comparator: Placebo<br>Placebo administered by IV infusion 8 times | Biological: Placebo<br>* Repeated IV infusions over 12 weeks (at weeks 0, 1, 2, 4, 6, 8, 10, 12)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Number of Participants with Adverse Events (Including SAEs and AEs leading to discontinuation) from Baseline through End of Trial Visit (Week 14) | Baseline through End of Trial Visit (Week 14) | 
| Number of Participants With Changes of Safety Parameters | Number of Participants with changes in vital signs, ECGs, Safety laboratory parameters (full blood count including white differential count, clinical chemistry, thyroid hormones, urinalysis, and faecal occult blood test), Development of anti-drug antibodies against BT063 (anti-BT063), Immunological status of potential viral and bacterial infections (HBV, HCV, HIV, tetanus, diphtheria tuberculosis), EBV / CMV Serology, Premature withdrawals. | Baseline through End of Trial Visit (Week 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Improvements of Joints | Number of Participants with 50% improvement of swollen/tender joints. A total of 66/68 joints was assessed for the swollen/tender joint count. A joint that is normal (no tenderness or swelling), without signs of inflammation will be graded as 0. A joint with tenderness will be graded as 1 for tender joint count and a joint with swelling will be graded as 1 for swollen joint count. Joints suspected or known to have ischemic osteonecrosis are not to be taken into consideration. Higher scores indicate more disease activity. | At week14 and week 28 | 
| Number of Participants With Improvement of Skin | Number of Participants with 50% improvement in Cutaneous Lupus Erythematosus Disease Area and Sensitivity Index (CLASI) Activity score. The CLASI is an assessment over 13 body regions (scalp, ears, nose - including malar area, rest of the face, V-area neck - frontal, post. neck & shoulders, chest, abdomen, back and buttocks, arms, hands, legs, feet) and consists of 2 scores: total activity score and total damage score. Only the activity score was used in this study. The minimum score possible on this scale is 0 and the maximum score is 70. The higher scores mean a worse outcome. | At week14 and week 28 | 
| Percent Changes in Systemic Lupus Erythematosus Disease Activity Index 2000 | Percent changes in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from baseline SLEDAI-2K score. The SLEDAI-2K is a global index that measures SLE disease activity. It includes 24 items for the 9 organs/systems. Scores range from 0 to 105; a score of 6 is considered clinically important. The index measures disease activity within the last 10 days. Higher scores mean worse outcome. Negative percent change means reduced disease activity. | Baseline to week 14 and at week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, Lupus, IL10, IL-10, BT063, BT-063