Systemic Lupus Erythematosus
Conditions
Keywords
SLE, Lupus, IL10, IL-10, BT063, BT-063
Brief summary
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
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.
Interventions
BIOLOGICALBT063
Repeated IV infusions over 12 weeks (at weeks 0, 1, 2, 4, 6, 8, 10, 12)
BIOLOGICALPlacebo
Repeated IV infusions over 12 weeks (at weeks 0, 1, 2, 4, 6, 8, 10, 12)
Sponsors
Biotest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Baseline through End of Trial Visit (Week 14) | Number of Participants with Adverse Events (Including SAEs and AEs leading to discontinuation) from Baseline through End of Trial Visit (Week 14) |
| Number of Participants With Changes of Safety Parameters | Baseline through End of Trial Visit (Week 14) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvements of Joints | At week14 and week 28 | 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. |
| Number of Participants With Improvement of Skin | At week14 and week 28 | 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. |
| Percent Changes in Systemic Lupus Erythematosus Disease Activity Index 2000 | Baseline to week 14 and at week 28 | 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. |
Countries
Belarus, Georgia, Poland, Serbia
Participant flow
Recruitment details
In total 36 subjects were enrolled in study parts I and II (18 in part I and 18 in part II). 12 subjects in part I received 50 mg BT063, 12 subjects in part II received 100 mg BT063. 6 subjects in part I and 6 subjects in part II received Placebo and were pooled for analysis. Only final results and no partial or interim results are presented.
Participants by arm
| Arm | Count |
|---|---|
| BT063 50 mg 50 mg BT063 administered by intravenous (IV) infusion 8 times
BT063: Repeated IV infusions over 12 weeks (at weeks 0, 1, 2, 4, 6, 8, 10, 12) | 12 |
| BT063 100 mg 100 mg BT063 administered by intravenous (IV) infusion 8 times
BT063: Repeated IV infusions over 12 weeks (at weeks 0, 1, 2, 4, 6, 8, 10, 12) | 12 |
| Placebo Placebo administered by IV infusion 8 times
Placebo: Repeated IV infusions over 12 weeks (at weeks 0, 1, 2, 4, 6, 8, 10, 12) | 12 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | BT063 50 mg | BT063 100 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 12.77 | 50.7 years STANDARD_DEVIATION 7.18 | 48.6 years STANDARD_DEVIATION 13.5 | 45.6 years STANDARD_DEVIATION 12.63 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 12 Participants | 12 Participants | 36 Participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 12 Participants | 33 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 2 / 12 | 6 / 12 | 6 / 12 |
| serious Total, serious adverse events | 1 / 12 | 1 / 12 | 0 / 12 |
Outcome results
Primary
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)
Time frame: Baseline through End of Trial Visit (Week 14)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BT063 50 mg | Number of Participants With Adverse Events | Subjects with TEAEs | 5 Participants |
| BT063 50 mg | Number of Participants With Adverse Events | Subjects with severe TEAEs | 0 Participants |
| BT063 50 mg | Number of Participants With Adverse Events | Subjects with TEAEs leading to death | 0 Participants |
| BT063 50 mg | Number of Participants With Adverse Events | Subjects with TEAEs leading to early termination | 1 Participants |
| BT063 50 mg | Number of Participants With Adverse Events | Subjects with treatment-emergent SAEs | 1 Participants |
| BT063 50 mg | Number of Participants With Adverse Events | Subjects with drug-related TEAEs | 1 Participants |
| BT063 100 mg | Number of Participants With Adverse Events | Subjects with severe TEAEs | 0 Participants |
| BT063 100 mg | Number of Participants With Adverse Events | Subjects with drug-related TEAEs | 2 Participants |
| BT063 100 mg | Number of Participants With Adverse Events | Subjects with TEAEs leading to early termination | 0 Participants |
| BT063 100 mg | Number of Participants With Adverse Events | Subjects with treatment-emergent SAEs | 1 Participants |
| BT063 100 mg | Number of Participants With Adverse Events | Subjects with TEAEs leading to death | 0 Participants |
| BT063 100 mg | Number of Participants With Adverse Events | Subjects with TEAEs | 8 Participants |
| Placebo | Number of Participants With Adverse Events | Subjects with TEAEs leading to death | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Subjects with TEAEs | 8 Participants |
| Placebo | Number of Participants With Adverse Events | Subjects with TEAEs leading to early termination | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Subjects with treatment-emergent SAEs | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Subjects with drug-related TEAEs | 0 Participants |
| Placebo | Number of Participants With Adverse Events | Subjects with severe TEAEs | 0 Participants |
Primary
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.
Time frame: Baseline through End of Trial Visit (Week 14)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BT063 50 mg | Number of Participants With Changes of Safety Parameters | 0 Participants |
| BT063 100 mg | Number of Participants With Changes of Safety Parameters | 0 Participants |
| Placebo | Number of Participants With Changes of Safety Parameters | 0 Participants |
Secondary
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.
Time frame: At week14 and week 28
Population: Intension-To-Treat Set included 36 subjects (12 of each Group). At week 14, 1 subject in Placebo Group had no end of Treatment result; at week 28, 1 subject of 50 mg and 2 subjects of Placebo had no results. The efficacy outcome was based on observed cases.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BT063 50 mg | Number of Participants With Improvement of Skin | 50% improvement in CLASI Activity score at week 28 | 7 Participants |
| BT063 50 mg | Number of Participants With Improvement of Skin | 50% improvement in CLASI Activity score at week 14 | 6 Participants |
| BT063 100 mg | Number of Participants With Improvement of Skin | 50% improvement in CLASI Activity score at week 14 | 5 Participants |
| BT063 100 mg | Number of Participants With Improvement of Skin | 50% improvement in CLASI Activity score at week 28 | 4 Participants |
| Placebo | Number of Participants With Improvement of Skin | 50% improvement in CLASI Activity score at week 14 | 3 Participants |
| Placebo | Number of Participants With Improvement of Skin | 50% improvement in CLASI Activity score at week 28 | 3 Participants |
Secondary
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.
Time frame: At week14 and week 28
Population: Intension-To-Treat Set included 36 subjects (12 of each Group). At week 14, 1 subject in Placebo Group had no end of Treatment result; at week 28, 1 subject of 50 mg and 2 subjects of Placebo had no results. The efficacy outcome was based on observed cases.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BT063 50 mg | Number of Participants With Improvements of Joints | 50% improvement in swollen joints at week 14 | 8 Participants |
| BT063 50 mg | Number of Participants With Improvements of Joints | 50% improvement in tender joints at week 28 | 7 Participants |
| BT063 50 mg | Number of Participants With Improvements of Joints | 50% improvement in tender joints at week 14 | 5 Participants |
| BT063 50 mg | Number of Participants With Improvements of Joints | 50% improvement in swollen joints at week 28 | 7 Participants |
| BT063 100 mg | Number of Participants With Improvements of Joints | 50% improvement in swollen joints at week 28 | 4 Participants |
| BT063 100 mg | Number of Participants With Improvements of Joints | 50% improvement in tender joints at week 14 | 7 Participants |
| BT063 100 mg | Number of Participants With Improvements of Joints | 50% improvement in tender joints at week 28 | 6 Participants |
| BT063 100 mg | Number of Participants With Improvements of Joints | 50% improvement in swollen joints at week 14 | 5 Participants |
| Placebo | Number of Participants With Improvements of Joints | 50% improvement in tender joints at week 28 | 6 Participants |
| Placebo | Number of Participants With Improvements of Joints | 50% improvement in swollen joints at week 14 | 8 Participants |
| Placebo | Number of Participants With Improvements of Joints | 50% improvement in swollen joints at week 28 | 7 Participants |
| Placebo | Number of Participants With Improvements of Joints | 50% improvement in tender joints at week 14 | 6 Participants |
Secondary
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.
Time frame: Baseline to week 14 and at week 28
Population: Intension-To-Treat Set included 36 subjects (12 of each Group). At week 14, 1 subject in Placebo Group had no end of Treatment result; at week 28, 1 subject of 50 mg and 2 subjects of Placebo had no results. The efficacy outcome was based on observed cases.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BT063 50 mg | Percent Changes in Systemic Lupus Erythematosus Disease Activity Index 2000 | Percent changes in SLEDAI-2K scores at week 14 | -29.3 percentage of change | Standard Deviation 31.43 |
| BT063 50 mg | Percent Changes in Systemic Lupus Erythematosus Disease Activity Index 2000 | Percent changes in SLEDAI-2K scores at week 28 | -28.9 percentage of change | Standard Deviation 36.05 |
| BT063 100 mg | Percent Changes in Systemic Lupus Erythematosus Disease Activity Index 2000 | Percent changes in SLEDAI-2K scores at week 14 | -18.0 percentage of change | Standard Deviation 37.304 |
| BT063 100 mg | Percent Changes in Systemic Lupus Erythematosus Disease Activity Index 2000 | Percent changes in SLEDAI-2K scores at week 28 | -24.4 percentage of change | Standard Deviation 35.19 |
| Placebo | Percent Changes in Systemic Lupus Erythematosus Disease Activity Index 2000 | Percent changes in SLEDAI-2K scores at week 28 | -13.5 percentage of change | Standard Deviation 32.36 |
| Placebo | Percent Changes in Systemic Lupus Erythematosus Disease Activity Index 2000 | Percent changes in SLEDAI-2K scores at week 14 | -18.2 percentage of change | Standard Deviation 25.75 |