A Phase 2 Efficacy and Safety Study of Dapirolizumab Pegol (DZP) in Systemic Lupus Erythematosus

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study Followed by an Observational Period to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus (SLE)
• Intervention / Treatment: Drug: Placebo; Drug: Dapirolizumab pegol (DZP)

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • Sl0023 101
  • Plovdiv, Bulgaria
    • Sl0023 102
• Chile
  • Providencia, Chile
    • Sl0023 202
  • Providencia, Chile
    • Sl0023 203
  • Puerto Varas, Chile
    • Sl0023 201
  • Vina del Mar, Chile
    • Sl0023 204
• Colombia
  • Barranquilla, Colombia
    • Sl0023 213
  • Bogotá, Colombia
    • Sl0023 212
  • Bogotá, Colombia
    • Sl0023 214
  • Bucaramanga, Colombia
    • Sl0023 216
  • Chía, Colombia
    • Sl0023 211
  • Medellín, Colombia
    • Sl0023 215
• Germany
  • Hannover, Germany
    • Sl0023 341
  • Leipzig, Germany
    • Sl0023 113
• Hungary
  • Debrecen, Hungary
    • Sl0023 124
• Mexico
  • Guadalajara, Mexico
    • Sl0023 225
  • León, Mexico
    • Sl0023 224
  • Mexico, Mexico
    • Sl0023 221
  • San Luis Potosí, Mexico
    • Sl0023 222
• Peru
  • Arequipa, Peru
    • Sl0023 232
  • Lima, Peru
    • Sl0023 231
  • Lima, Peru
    • Sl0023 234
  • Lima, Peru
    • Sl0023 235
• Poland
  • Bytom, Poland
    • Sl0023 133
  • Lublin, Poland
    • Sl0023 136
  • Poznan, Poland
    • Sl0023 131
  • Sosnowiec, Poland
    • Sl0023 134
  • Warszawa, Poland
    • Sl0023 135
  • Łódź, Poland
    • Sl0023 138
• Romania
  • Brasov, Romania
    • Sl0023 146
  • Bucuresti, Romania
    • Sl0023 142
  • Cluj-Napoca, Romania
    • Sl0023 144
  • Galati, Romania
    • Sl0023 141
• Russian Federation
  • Kazan, Russian Federation
    • Sl0023 157
  • Kemerovo, Russian Federation
    • Sl0023 156
  • Saint Petersburg, Russian Federation
    • Sl0023 152
  • Voronezh, Russian Federation
    • Sl0023 155
  • Yaroslavl', Russian Federation
    • Sl0023 151
  • Yekaterinburg, Russian Federation
    • Sl0023 153
• Spain
  • Barcelona, Spain
    • Sl0023 161
  • Madrid, Spain
    • Sl0023 162
  • Tenerife, Spain
    • Sl0023 166
• Ukraine
  • Kyiv, Ukraine
    • Sl0023 172
  • Kyiv, Ukraine
    • Sl0023 175
  • Odessa, Ukraine
    • Sl0023 171
  • Vinnytsya, Ukraine
    • Sl0023 173
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Sl0023 312
  • California
    • El Cajon, California, United States, 92020
      • Sl0023 307
    • El Cajon, California, United States, 92020
      • Sl0023 309
    • Huntington Beach, California, United States, 92646
      • Sl0023 323
    • Los Angeles, California, United States, 90048
      • Sl0023 311
    • Thousand Oaks, California, United States, 91360
      • Sl0023 314
    • Upland, California, United States, 91786
      • Sl0023 302
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Sl0023 326
  • Florida
    • Clearwater, Florida, United States, 33765
      • Sl0023 304
    • DeBary, Florida, United States, 32713
      • Sl0023 322
    • Miami, Florida, United States, 33136
      • Sl0023 321
    • Miami Lakes, Florida, United States, 33014
      • Sl0023 301
    • Palm Harbor, Florida, United States, 34684
      • Sl0023 319
    • Tampa, Florida, United States, 33603
      • Sl0023 310
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Sl0023 324
    • Stockbridge, Georgia, United States, 30281
      • Sl0023 327
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Sl0023 320
  • New Mexico
    • Albuquerque, New Mexico, United States, 87104
      • Sl0023 306
  • New York
    • Lake Success, New York, United States, 11042
      • Sl0023 313
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73101
      • Sl0023 305
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Sl0023 315
    • Memphis, Tennessee, United States, 38119
      • Sl0023 308
  • Texas
    • Amarillo, Texas, United States, 79124
      • Sl0023 317
    • Houston, Texas, United States, 77034
      • Sl0023 303
  • Washington
    • Spokane, Washington, United States, 99204
      • Sl0023 328

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo in a specified sequence for a total of 24 weeks	Drug: Placebo; Solution for infusion, 0,9% saline
Experimental: DZP dose 1; Dapirolizumab pegol (DZP) dose 1 in a specified sequence for a total of 24 weeks	Drug: Dapirolizumab pegol (DZP); Solution for infusion
Experimental: DZP dose 2; Dapirolizumab pegol (DZP) dose 2 in a specified sequence for a total of 24 weeks	Drug: Dapirolizumab pegol (DZP); Solution for infusion
Experimental: DZP dose 3; Dapirolizumab pegol (DZP) dose 3 in a specified sequence for a total of 24 weeks	Drug: Dapirolizumab pegol (DZP); Solution for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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: 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.; No worsening in Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K), defined as no increase in SLEDAI-2K total score.; 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).; No disallowed changes in concomitant medications, mainly including increases in corticosteroids, immunosuppressants, and antimalarials.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants With BICLA (mNRI) Response in the Individual Dose Groups at Week 24	BICLA response was defined as meeting all of the following criteria: 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.; No worsening in Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K), defined as no increase in SLEDAI-2K total score.; 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).; No disallowed changes in concomitant medications, mainly including increases in corticosteroids, immunosuppressants, and antimalarials.	Week 24
Percentage of Participants With at Least One Adverse Events (AEs)	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.	From Baseline (Week 1) until end of the study (Week 48)
Percentage of Participants With a Serious Adverse Event (SAE)	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.	From Baseline (Week 1) until end of the study (Week 48)
Percentage of Participants With at Least One Adverse Events (AEs) of Interest	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.	From Baseline (Week 1) until end of the study (Week 48)
Percentage of Participants Who Permanently Withdrew of Study Drug Due to an Adverse Event (AE)	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.	From Baseline (Week 1) until end of the study (Week 48)
Mean Change From Baseline in Systolic Blood Pressure	Blood pressure was measured in millimetre of mercury (mmHg).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Diastolic Blood Pressure	Blood pressure was measured in millimetre of mercury (mmHg).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Pulse Rate	Pulse Rate was measured in beats per minute (beats/min).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Temperature	Temperature was measured in Grad Celsius (°C).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Weight	Weight was measured in kilograms (kg).	Baseline (Week 1), Week 4, Week 8, Week 12, Week 16, and Week 20
Mean Change From Baseline in Height	Height was measured in centimeters (cm).	From Baseline (Week 1) to Week 48
Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormal Findings	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).	Screening, Week 4, Week 24, Week 28 and Week 48
Mean Change From Baseline in Hemoglobin	Hemoglobin was measured in grams per liter (g/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Hematocrit	Hematocrit was measured in volume percentage (%) of red blood cells in blood.	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Erythrocytes	Erythrocytes was measured in number of erythrocytes per liter (10^12/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Erythrocytes Mean Corpuscular Volume	Erythrocytes Mean Corpuscular Volume was measured in femtolitres (fL).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration	Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration was measured in grams per liter (g/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin	Erythrocytes Mean Corpuscular Hemoglobin was measured in picograms (pg).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Leukocytes	Leukocytes was measured in number of leukocytes per liter (10^9/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Basophils	Basophils was measured in number of basophils per liter (10^9/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Basophils/Leukocytes	Basophils/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Eosinophils	Eosinophils was measured in number of eosinophils per liter (10^9/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Eosinophils/Leukocytes	Eosinophils/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Lymphocytes	Lymphocytes was measured in number of lymphocytes per liter (10^9/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Lymphocytes/Leukocytes	Lymphocytes/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Monocytes	Monocytes was measured in number of monocytes per liter (10^9/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Monocytes/Leukocytes	Monocytes/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Neutrophils	Neutrophils was measured in number of neutrophils per liter (10^9/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Neutrophils/Leukocytes	Neutrophils/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Platelets	Platelets was measured in number of platelets per liter (10^9/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Cluster of Differentiation 3 (CD3)	Cluster of differentiation 3 (CD3) was measured in cells per microliter (cells/µL).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in CD3/Lymphocytes	CD3/Lymphocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Cluster of Differentiation 19 (CD19)	Cluster of differentiation 19 (CD19) was measured in cells per microliter (cells/µL).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in CD19/Lymphocytes	CD19/Lymphocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Aspartate Aminotransferase	Aspartate Aminotransferase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Alanine Aminotransferase	Alanine Aminotransferase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Alkaline Phosphatase	Alkaline Phosphatase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Gamma Glutamyl Transferase	Gamma Glutamyl Transferase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Bilirubin	Bilirubin was measured in micromols per liter (µmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Direct Bilirubin	Direct Bilirubin was measured in micromols per liter (µmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Lactate Dehydrogenase	Lactate Dehydrogenase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Creatinine	Creatinine was measured in micromols per liter (µmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Urea Nitrogen	Urea Nitrogen was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Sodium	Sodium was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Potassium	Potassium was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Calcium	Calcium was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Phosphate	Phosphate was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Cholesterol	Cholesterol was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Triglycerides	Triglycerides was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Protein	Protein was measured in grams per liter (g/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Albumin	Albumin was measured in grams per liter (g/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Glucose	Glucose was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Lipase, Pancreatic	Lipase, Pancreatic was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in Creatine Kinase	Creatine Kinase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Mean Change From Baseline in pH		From Baseline (Week 1) to Week 48
Mean Change From Baseline in Erythrocytes (/HPF)		From Baseline (Week 1) to Week 48
Mean Change From Baseline in Leukocytes (/HPF)		From Baseline (Week 1) to Week 48

Collaborators and Investigators

• Sponsor: UCB Biopharma S.P.R.L.

Publications and helpful links

General Publications

• Morel T, Cano S, Bartlett SJ, Gordon C, Haier B, Regnault A, Schneider M, Stach C, Cleanthous S. The FATIGUE-PRO: a new patient-reported outcome instrument to quantify fatigue in patients affected by systemic lupus erythematosus. Rheumatology (Oxford). 2022 Aug 3;61(8):3329-3340. doi: 10.1093/rheumatology/keab920.

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2016
• Primary Completion (Actual): May 31, 2018
• Study Completion (Actual): November 19, 2018

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 14, 2016
• First Posted (Estimate): June 17, 2016

Study Record Updates

• Last Update Posted (Actual): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus (SLE); Dapirolizumab Pegol (DZP)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: SL0023; 2015-004457-40 (EudraCT Number)