A Phase 2 Efficacy and Safety Study of Dapirolizumab Pegol (DZP) in Systemic Lupus Erythematosus
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Interventions
- Drug: PlaceboDrug: Dapirolizumab pegol (DZP)
- Registration Number
- NCT02804763
- Lead Sponsor
- UCB Biopharma S.P.R.L.
- Brief Summary
The purpose is to evaluate the efficacy and safety of three different doses of Dapirolizumab Pegol (DZP) versus placebo in adult subjects with moderately to severely active systemic Lupus Erythematosus.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 182
-
Clinical diagnosis of Systemic Lupus Erythematosus (SLE) confirmed by Systemic Lupus International Collaborating Clinics (SLICC) classification criteria
-
Moderate to severe SLE disease activity
-
Evidence for at least 1 of the following SLE markers:
- Anti-dsDNA antibodies confirmed by central laboratory or
- Low complement confirmed by central laboratory or
- Antinuclear antibody (ANA) titer of >= 1:80 in combination with at least 1 of the following: Historical positivity for anti-dsDNA or Positivity for extractable nuclear antigen (anti-ENA) confirmed by central laboratory
-
The subject is receiving stable SLE standard-of-care medication
- Mixed connective tissue disease, scleroderma, and/or overlap syndromes of SLE
- Subjects with severe neuropsychiatric SLE or other neurological symptoms that in the opinion of the Investigator, would prevent the subject from completing protocol required procedures and assessments.
- New or worsening Class III or IV lupus nephritis
- Chronic kidney failure stage 3b
- Evidence of human immunodeficiency virus (HIV) infection, agammaglobulinemias, T-cell deficiencies, or human T-cell lymphotropic virus-1 infection at any time prior to or during the study
- Clinically significant active or latent infection (eg. chronic viral hepatitis B or C)
- Known tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent TB (LTB) infection
- Live/live attenuated vaccines within 6 weeks prior to the first study drug infusion (Visit 2) or who plan to receive these vaccines during the study or 12 weeks after the final dose of study drug
- History of thromboembolic events within 12 months of screening
- Subject has used protocol defined prohibited medications
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo in a specified sequence for a total of 24 weeks DZP dose 1 Dapirolizumab pegol (DZP) Dapirolizumab pegol (DZP) dose 1 in a specified sequence for a total of 24 weeks DZP dose 3 Dapirolizumab pegol (DZP) Dapirolizumab pegol (DZP) dose 3 in a specified sequence for a total of 24 weeks DZP dose 2 Dapirolizumab pegol (DZP) Dapirolizumab pegol (DZP) dose 2 in a specified sequence for a total of 24 weeks
- Primary Outcome Measures
Name Time Method Percentage of Participants With British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004)-Based Composite Lupus Assessment (BICLA) (mNRI) Response Across 3 Doses of Dapirolizumab Pegol (DZP) and Placebo (PBO) at Week 24 Week 24 The primary efficacy variable was assessed by establishing if there was a dose response relationship between BICLA response at Week 24 and dose, using Multiple Comparison Procedure - Modelling (MCP-Mod). Four candidate dose-response models were evaluated: a linear model, a logistic model, and 2 Emax models, and the MCP-Mod methodology controlled for multiplicity.
BICLA response was defined as meeting all of the following criteria:
1. BILAG 2004 improvement: A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤ 1 new B.
2. No worsening in Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K), defined as no increase in SLEDAI-2K total score.
3. No worsening in Physician's Global Assessment of Disease Activity (PGA), defined as \< 10 millimeter (mm) increase on a 100 mm visual analog scale (VAS).
4. No disallowed changes in concomitant medications, mainly including increases in corticosteroids, immunosuppressants, and antimalarials.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline in Diastolic Blood Pressure From Baseline (Week 1) to Week 48 Blood pressure was measured in millimetre of mercury (mmHg).
Percentage of Participants Who Permanently Withdrew of Study Drug Due to an Adverse Event (AE) From Baseline (Week 1) until end of the study (Week 48) An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An adverse event (AE) was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AEs that occurred during the study were considered related unless clearly unrelated.
Mean Change From Baseline in Erythrocytes From Baseline (Week 1) to Week 48 Erythrocytes was measured in number of erythrocytes per liter (10\^12/L).
The Percentage of Participants With BICLA (mNRI) Response in the Individual Dose Groups at Week 24 Week 24 BICLA response was defined as meeting all of the following criteria:
1. BILAG 2004 improvement: A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤ 1 new B.
2. No worsening in Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K), defined as no increase in SLEDAI-2K total score.
3. No worsening in Physician's Global Assessment of Disease Activity (PGA), defined as \< 10 millimeter (mm) increase on a 100 mm visual analog scale (VAS).
4. No disallowed changes in concomitant medications, mainly including increases in corticosteroids, immunosuppressants, and antimalarials.Percentage of Participants With at Least One Adverse Events (AEs) From Baseline (Week 1) until end of the study (Week 48) An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An adverse event (AE) was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AEs that occurred during the study were considered related unless clearly unrelated.
Mean Change From Baseline in Systolic Blood Pressure From Baseline (Week 1) to Week 48 Blood pressure was measured in millimetre of mercury (mmHg).
Mean Change From Baseline in Eosinophils/Leukocytes From Baseline (Week 1) to Week 48 Eosinophils/Leukocytes was measured in percentages (%).
Mean Change From Baseline in Basophils/Leukocytes From Baseline (Week 1) to Week 48 Basophils/Leukocytes was measured in percentages (%).
Mean Change From Baseline in Basophils From Baseline (Week 1) to Week 48 Basophils was measured in number of basophils per liter (10\^9/L).
Mean Change From Baseline in Pulse Rate From Baseline (Week 1) to Week 48 Pulse Rate was measured in beats per minute (beats/min).
Mean Change From Baseline in Temperature From Baseline (Week 1) to Week 48 Temperature was measured in Grad Celsius (°C).
Mean Change From Baseline in Weight Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, and Week 20 Weight was measured in kilograms (kg).
Mean Change From Baseline in Hemoglobin From Baseline (Week 1) to Week 48 Hemoglobin was measured in grams per liter (g/L).
Mean Change From Baseline in Hematocrit From Baseline (Week 1) to Week 48 Hematocrit was measured in volume percentage (%) of red blood cells in blood.
Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormal Findings Screening, Week 4, Week 24, Week 28 and Week 48 Twelve-lead ECG assessments should have been performed prior to dosing (if applicable) and prior to obtaining pharmacokinetic (PK) or other laboratory samples. Electrocardiograms were recorded digitally and read by the Investigator for recording in the electronic Case Report Form (eCRF).
Percentage of Participants With a Serious Adverse Event (SAE) From Baseline (Week 1) until end of the study (Week 48) A Serious Adverse Event (SAE) must have met 1 or more of the following criteria:
* Death
* Life threatening
* Significant or persistent disability/incapacity
* Congenital anomaly/birth defect (including that occurring in a fetus)
* Important medical event that, based upon appropriate medical judgment, may have jeopardized the study participant, and may have required medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious
* Initial inpatient hospitalization or prolongation of hospitalization.Percentage of Participants With at Least One Adverse Events (AEs) of Interest From Baseline (Week 1) until end of the study (Week 48) Adverse events of interest (AEOI) were identified by the Investigator based on definitions per protocol, documented on the electronic Case Report Form (eCRF), adequately monitored, and source controlled.
AEOI (regardless of seriousness):
* Moderate to severe infections, including opportunistic infections and tuberculosis (TB)
* Infusion reactions (including hypersensitivity and anaphylaxis)
* Thromboembolic events (including but not limited to cardiovascular events, stroke, myocardial infarction, pulmonary embolism, and deep vein thrombosis)
* Prespecified neurological events: severe and/or serious headache, positional headache, cranial nerve dysfunction, or signs and symptoms of meningitis (photophobia, neck stiffness)
* Malignancies.Mean Change From Baseline in Height From Baseline (Week 1) to Week 48 Height was measured in centimeters (cm).
Mean Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration From Baseline (Week 1) to Week 48 Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration was measured in grams per liter (g/L).
Mean Change From Baseline in Alkaline Phosphatase From Baseline (Week 1) to Week 48 Alkaline Phosphatase was measured in units per liter (U/L).
Mean Change From Baseline in Creatinine From Baseline (Week 1) to Week 48 Creatinine was measured in micromols per liter (µmol/L).
Mean Change From Baseline in Sodium From Baseline (Week 1) to Week 48 Sodium was measured in millimoles per liter (mmol/L).
Mean Change From Baseline in Albumin From Baseline (Week 1) to Week 48 Albumin was measured in grams per liter (g/L).
Mean Change From Baseline in Triglycerides From Baseline (Week 1) to Week 48 Triglycerides was measured in millimoles per liter (mmol/L).
Mean Change From Baseline in Erythrocytes Mean Corpuscular Volume From Baseline (Week 1) to Week 48 Erythrocytes Mean Corpuscular Volume was measured in femtolitres (fL).
Mean Change From Baseline in Leukocytes From Baseline (Week 1) to Week 48 Leukocytes was measured in number of leukocytes per liter (10\^9/L).
Mean Change From Baseline in Neutrophils From Baseline (Week 1) to Week 48 Neutrophils was measured in number of neutrophils per liter (10\^9/L).
Mean Change From Baseline in Neutrophils/Leukocytes From Baseline (Week 1) to Week 48 Neutrophils/Leukocytes was measured in percentages (%).
Mean Change From Baseline in CD3/Lymphocytes From Baseline (Week 1) to Week 48 CD3/Lymphocytes was measured in percentages (%).
Mean Change From Baseline in Bilirubin From Baseline (Week 1) to Week 48 Bilirubin was measured in micromols per liter (µmol/L).
Mean Change From Baseline in Lactate Dehydrogenase From Baseline (Week 1) to Week 48 Lactate Dehydrogenase was measured in units per liter (U/L).
Mean Change From Baseline in Urea Nitrogen From Baseline (Week 1) to Week 48 Urea Nitrogen was measured in millimoles per liter (mmol/L).
Mean Change From Baseline in Cholesterol From Baseline (Week 1) to Week 48 Cholesterol was measured in millimoles per liter (mmol/L).
Mean Change From Baseline in Protein From Baseline (Week 1) to Week 48 Protein was measured in grams per liter (g/L).
Mean Change From Baseline in Creatine Kinase From Baseline (Week 1) to Week 48 Creatine Kinase was measured in units per liter (U/L).
Mean Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin From Baseline (Week 1) to Week 48 Erythrocytes Mean Corpuscular Hemoglobin was measured in picograms (pg).
Mean Change From Baseline in Eosinophils From Baseline (Week 1) to Week 48 Eosinophils was measured in number of eosinophils per liter (10\^9/L).
Mean Change From Baseline in Lymphocytes From Baseline (Week 1) to Week 48 Lymphocytes was measured in number of lymphocytes per liter (10\^9/L).
Mean Change From Baseline in Cluster of Differentiation 19 (CD19) From Baseline (Week 1) to Week 48 Cluster of differentiation 19 (CD19) was measured in cells per microliter (cells/µL).
Mean Change From Baseline in Aspartate Aminotransferase From Baseline (Week 1) to Week 48 Aspartate Aminotransferase was measured in units per liter (U/L).
Mean Change From Baseline in Alanine Aminotransferase From Baseline (Week 1) to Week 48 Alanine Aminotransferase was measured in units per liter (U/L).
Mean Change From Baseline in Gamma Glutamyl Transferase From Baseline (Week 1) to Week 48 Gamma Glutamyl Transferase was measured in units per liter (U/L).
Mean Change From Baseline in Potassium From Baseline (Week 1) to Week 48 Potassium was measured in millimoles per liter (mmol/L).
Mean Change From Baseline in Lipase, Pancreatic From Baseline (Week 1) to Week 48 Lipase, Pancreatic was measured in units per liter (U/L).
Mean Change From Baseline in pH From Baseline (Week 1) to Week 48 Mean Change From Baseline in Leukocytes (/HPF) From Baseline (Week 1) to Week 48 Mean Change From Baseline in Lymphocytes/Leukocytes From Baseline (Week 1) to Week 48 Lymphocytes/Leukocytes was measured in percentages (%).
Mean Change From Baseline in Monocytes/Leukocytes From Baseline (Week 1) to Week 48 Monocytes/Leukocytes was measured in percentages (%).
Mean Change From Baseline in Platelets From Baseline (Week 1) to Week 48 Platelets was measured in number of platelets per liter (10\^9/L).
Mean Change From Baseline in Cluster of Differentiation 3 (CD3) From Baseline (Week 1) to Week 48 Cluster of differentiation 3 (CD3) was measured in cells per microliter (cells/µL).
Mean Change From Baseline in Direct Bilirubin From Baseline (Week 1) to Week 48 Direct Bilirubin was measured in micromols per liter (µmol/L).
Mean Change From Baseline in Calcium From Baseline (Week 1) to Week 48 Calcium was measured in millimoles per liter (mmol/L).
Mean Change From Baseline in Phosphate From Baseline (Week 1) to Week 48 Phosphate was measured in millimoles per liter (mmol/L).
Mean Change From Baseline in Monocytes From Baseline (Week 1) to Week 48 Monocytes was measured in number of monocytes per liter (10\^9/L).
Mean Change From Baseline in CD19/Lymphocytes From Baseline (Week 1) to Week 48 CD19/Lymphocytes was measured in percentages (%).
Mean Change From Baseline in Glucose From Baseline (Week 1) to Week 48 Glucose was measured in millimoles per liter (mmol/L).
Mean Change From Baseline in Erythrocytes (/HPF) From Baseline (Week 1) to Week 48
Trial Locations
- Locations (71)
Sl0023 135
🇵🇱Warszawa, Poland
Sl0023 310
🇺🇸Tampa, Florida, United States
Sl0023 312
🇺🇸Birmingham, Alabama, United States
Sl0023 304
🇺🇸Clearwater, Florida, United States
Sl0023 301
🇺🇸Miami Lakes, Florida, United States
Sl0023 321
🇺🇸Miami, Florida, United States
Sl0023 320
🇺🇸Idaho Falls, Idaho, United States
Sl0023 305
🇺🇸Oklahoma City, Oklahoma, United States
Sl0023 303
🇺🇸Houston, Texas, United States
Sl0023 102
🇧🇬Plovdiv, Bulgaria
Sl0023 311
🇺🇸Los Angeles, California, United States
Sl0023 307
🇺🇸El Cajon, California, United States
Sl0023 309
🇺🇸El Cajon, California, United States
Sl0023 323
🇺🇸Huntington Beach, California, United States
Sl0023 326
🇺🇸New Haven, Connecticut, United States
Sl0023 314
🇺🇸Thousand Oaks, California, United States
Sl0023 302
🇺🇸Upland, California, United States
Sl0023 322
🇺🇸DeBary, Florida, United States
Sl0023 319
🇺🇸Palm Harbor, Florida, United States
Sl0023 327
🇺🇸Stockbridge, Georgia, United States
Sl0023 324
🇺🇸Atlanta, Georgia, United States
Sl0023 313
🇺🇸Lake Success, New York, United States
Sl0023 306
🇺🇸Albuquerque, New Mexico, United States
Sl0023 315
🇺🇸Jackson, Tennessee, United States
Sl0023 308
🇺🇸Memphis, Tennessee, United States
Sl0023 317
🇺🇸Amarillo, Texas, United States
Sl0023 101
🇧🇬Plovdiv, Bulgaria
Sl0023 328
🇺🇸Spokane, Washington, United States
Sl0023 202
🇨🇱Providencia, Chile
Sl0023 203
🇨🇱Providencia, Chile
Sl0023 201
🇨🇱Puerto Varas, Chile
Sl0023 204
🇨🇱Vina del Mar, Chile
Sl0023 213
🇨🇴Barranquilla, Colombia
Sl0023 212
🇨🇴Bogotá, Colombia
Sl0023 216
🇨🇴Bucaramanga, Colombia
Sl0023 211
🇨🇴Chía, Colombia
Sl0023 214
🇨🇴Bogotá, Colombia
Sl0023 215
🇨🇴Medellín, Colombia
Sl0023 341
🇩🇪Hannover, Germany
Sl0023 113
🇩🇪Leipzig, Germany
Sl0023 225
🇲🇽Guadalajara, Mexico
Sl0023 124
🇭🇺Debrecen, Hungary
Sl0023 224
🇲🇽León, Mexico
Sl0023 222
🇲🇽San Luis Potosí, Mexico
Sl0023 221
🇲🇽Mexico, Mexico
Sl0023 231
🇵🇪Lima, Peru
Sl0023 232
🇵🇪Arequipa, Peru
Sl0023 234
🇵🇪Lima, Peru
Sl0023 235
🇵🇪Lima, Peru
Sl0023 131
🇵🇱Poznan, Poland
Sl0023 133
🇵🇱Bytom, Poland
Sl0023 136
🇵🇱Lublin, Poland
Sl0023 134
🇵🇱Sosnowiec, Poland
Sl0023 138
🇵🇱Łódź, Poland
Sl0023 146
🇷🇴Brasov, Romania
Sl0023 144
🇷🇴Cluj-Napoca, Romania
Sl0023 142
🇷🇴Bucuresti, Romania
Sl0023 141
🇷🇴Galati, Romania
Sl0023 157
🇷🇺Kazan, Russian Federation
Sl0023 151
🇷🇺Yaroslavl', Russian Federation
Sl0023 153
🇷🇺Yekaterinburg, Russian Federation
Sl0023 156
🇷🇺Kemerovo, Russian Federation
Sl0023 155
🇷🇺Voronezh, Russian Federation
Sl0023 152
🇷🇺Saint Petersburg, Russian Federation
Sl0023 161
🇪🇸Barcelona, Spain
Sl0023 172
🇺🇦Kyiv, Ukraine
Sl0023 162
🇪🇸Madrid, Spain
Sl0023 166
🇪🇸Tenerife, Spain
Sl0023 175
🇺🇦Kyiv, Ukraine
Sl0023 171
🇺🇦Odessa, Ukraine
Sl0023 173
🇺🇦Vinnytsya, Ukraine