Clinical study to evaluate the safety and tolerability of treatment with BT063 versus Placebo in Subjects with Systemic Lupus Erythematosus (BT063 in SLE)

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2014-005526-35-PL
• Date of registration: 10/08/2015
• Prospective Registration: Yes
• Primary sponsor: Biotest AG
• Public title: Clinical study to evaluate the safety and tolerability of treatment with BT063 versus Placebo in Subjects with Systemic Lupus Erythematosus (BT063 in SLE)
• Scientific title: A Prospective, Double-blind, Randomized, Placebo-controlled, Repeated dose, Multicentre Phase IIa Proof-of-Concept Study with BT063 in Subjects with Systemic Lupus Erythematosus (BT063 in SLE)
• Date of first enrolment: 12/09/2015
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005526-35
• 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 Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Georgia, Poland, Serbia

Contacts

• Name: Clinical Trial Information
• Affiliation: Biotest AG

• Name: Clinical Trial Information
• Affiliation: Biotest AG

Key inclusion & exclusion criteria

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)

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 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

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 × 109/L
- Leucocytes < 2.0 × 109/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



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Systemic Lupus Erythematosus
MedDRA version: 19.1 Level: LLT Classification code 10042947 Term: Systemic lupus erythematosus synd System Organ Class: 100000004859

Intervention(s)

Product Name: BT063
Product Code: BT063
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BT063
Current Sponsor code: BT063
Other descriptive name: BT063
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: Secondary objectives for both parts of the study are to:
•Evaluate the efficacy of 3 months of treatment with BT063 versus placebo as assessed by various disease activity indices including subject-reported outcomes
•Determine the pharmacokinetics (PK) of BT063
• Compare the pharmacodynamics (PD) of BT063 and placebo on various PD markers including biomarkers
•Determine the immunogenicity of BT063

Primary end point(s): Primary - Safety
•Incidence of Adverse events (Including SAEs and AEs leading to discontinuation) from Baseline through End of Trial Visit (Week 14)
•Changes from baseline through End of Trial Visit (Week 14) in:
oPhysical examinations
oVital signs
oECGs
oSafety laboratory parameters (full blood count including white differential count, clinical chemistry, thyroid hormones, urinalysis, and faecal occult blood test)
oDevelopment of anti-drug antibodies against BT063 (anti-BT063)
oImmunological status of potential viral and bacterial infections (HBV, HCV, HIV, tetanus, diphtheria tuberculosis)
oEBV / CMV Serology
o Premature withdrawals

Timepoint(s) of evaluation of this end point: From Baseline through End of Trial Visit (Week 14)

Main Objective: This study has 2 parts.
The primary objective of Part I of this study is to evaluate the safety and tolerability of 3 months of treatment with 50 mg BT063 versus placebo in subjects with SLE.
The primary objective of Part II of this study is to evaluate the safety and tolerability of either 25 mg, 50, mg or 100 mg BT063 versus placebo in subjects with SLE. The dose level for Part II will be determined based on an interim analysis conducted after the last subject of Part I has completed the treatment.

Secondary Outcome(s)

Secondary end point(s): Secondary –Efficacy

1.Fifty percent improvement of swollen/tender joints or 50% improvement in CLASI Activity score at week14 and week 28, depending on which was the more severe manifestation at baseline.
2.Percent changes in SLEDAI-2K scores from baseline to week 14 and at week 28
3.Flare rate and severity at week 14 and week 28 based on BILAG index A or B (flare is defined as the presence of 1 or more new BILAG A scores or 2 or more new BILAG B scores.)
4.Time to first flare
5.Number of patients requiring an increase in oral glucocorticosteroid dose before week 14
6.Physician’s Global Assessment, Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) and SF-36v2 Physical Component Score (PCS) at week 14 and week 28
7.ECLAM at week 14 and week 28

Timepoint(s) of evaluation of this end point: Points: 1, 2, 3, 6, 7: Week 14 and week 28
Point: 4: Time to first flare
Point: 5: before week 14

Secondary ID(s)

990

Source(s) of Monetary Support

Biotest AG