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

• ClinicalTrials.gov Identifier: NCT02804763
• Recruitment Status: Completed
• First Posted: June 17, 2016
• Results First Posted: June 30, 2021
• Last Update Posted: June 30, 2021
• Sponsor: UCB Biopharma S.P.R.L.
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma S.P.R.L. )

Tracking Information

• First Submitted Date: June 14, 2016
• First Posted Date: June 17, 2016
• Results First Submitted Date: April 19, 2021
• Results First Posted Date: June 30, 2021
• Last Update Posted Date: June 30, 2021
• Actual Study Start Date: June 2, 2016
• Actual Primary Completion Date: May 31, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 7, 2021)

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 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: June 14, 2016): Percentage of subjects with BICLA response across 3 doses of dapirolizumab pegol (DZP) and placebo (PBO) at Week 24 [ Time Frame: Week 24 ]

Current Secondary Outcome Measures (submitted: June 7, 2021)

• The Percentage of Participants With BICLA (mNRI) Response in the Individual Dose Groups at Week 24 [ Time Frame: 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) [ Time Frame: 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.
• Percentage of Participants With a Serious Adverse Event (SAE) [ Time Frame: 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 [ Time Frame: 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.
• Percentage of Participants Who Permanently Withdrew of Study Drug Due to an Adverse Event (AE) [ Time Frame: 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 [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Blood pressure was measured in millimetre of mercury (mmHg).
• Mean Change From Baseline in Diastolic Blood Pressure [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Blood pressure was measured in millimetre of mercury (mmHg).
• Mean Change From Baseline in Pulse Rate [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Pulse Rate was measured in beats per minute (beats/min).
• Mean Change From Baseline in Temperature [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Temperature was measured in Grad Celsius (°C).
• Mean Change From Baseline in Weight [ Time Frame: 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 Height [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Height was measured in centimeters (cm).
• Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormal Findings [ Time Frame: 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).
• Mean Change From Baseline in Hemoglobin [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Hemoglobin was measured in grams per liter (g/L).
• Mean Change From Baseline in Hematocrit [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Hematocrit was measured in volume percentage (%) of red blood cells in blood.
• Mean Change From Baseline in Erythrocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Erythrocytes was measured in number of erythrocytes per liter (10^12/L).
• Mean Change From Baseline in Erythrocytes Mean Corpuscular Volume [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Erythrocytes Mean Corpuscular Volume was measured in femtolitres (fL).
• Mean Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration [ Time Frame: 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 Erythrocytes Mean Corpuscular Hemoglobin [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Erythrocytes Mean Corpuscular Hemoglobin was measured in picograms (pg).
• Mean Change From Baseline in Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Leukocytes was measured in number of leukocytes per liter (10^9/L).
• Mean Change From Baseline in Basophils [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Basophils was measured in number of basophils per liter (10^9/L).
• Mean Change From Baseline in Basophils/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Basophils/Leukocytes was measured in percentages (%).
• Mean Change From Baseline in Eosinophils [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Eosinophils was measured in number of eosinophils per liter (10^9/L).
• Mean Change From Baseline in Eosinophils/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Eosinophils/Leukocytes was measured in percentages (%).
• Mean Change From Baseline in Lymphocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Lymphocytes was measured in number of lymphocytes per liter (10^9/L).
• Mean Change From Baseline in Lymphocytes/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Lymphocytes/Leukocytes was measured in percentages (%).
• Mean Change From Baseline in Monocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Monocytes was measured in number of monocytes per liter (10^9/L).
• Mean Change From Baseline in Monocytes/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Monocytes/Leukocytes was measured in percentages (%).
• Mean Change From Baseline in Neutrophils [ Time Frame: 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 [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Neutrophils/Leukocytes was measured in percentages (%).
• Mean Change From Baseline in Platelets [ Time Frame: 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) [ Time Frame: 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 CD3/Lymphocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  CD3/Lymphocytes was measured in percentages (%).
• Mean Change From Baseline in Cluster of Differentiation 19 (CD19) [ Time Frame: 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 CD19/Lymphocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
  CD19/Lymphocytes was measured in percentages (%).
• Mean Change From Baseline in Aspartate Aminotransferase [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Aspartate Aminotransferase was measured in units per liter (U/L).
• Mean Change From Baseline in Alanine Aminotransferase [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Alanine Aminotransferase was measured in units per liter (U/L).
• Mean Change From Baseline in Alkaline Phosphatase [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Alkaline Phosphatase was measured in units per liter (U/L).
• Mean Change From Baseline in Gamma Glutamyl Transferase [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Gamma Glutamyl Transferase was measured in units per liter (U/L).
• Mean Change From Baseline in Bilirubin [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Bilirubin was measured in micromols per liter (µmol/L).
• Mean Change From Baseline in Direct Bilirubin [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Direct Bilirubin was measured in micromols per liter (µmol/L).
• Mean Change From Baseline in Lactate Dehydrogenase [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Lactate Dehydrogenase was measured in units per liter (U/L).
• Mean Change From Baseline in Creatinine [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Creatinine was measured in micromols per liter (µmol/L).
• Mean Change From Baseline in Urea Nitrogen [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Urea Nitrogen was measured in millimoles per liter (mmol/L).
• Mean Change From Baseline in Sodium [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Sodium was measured in millimoles per liter (mmol/L).
• Mean Change From Baseline in Potassium [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Potassium was measured in millimoles per liter (mmol/L).
• Mean Change From Baseline in Calcium [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Calcium was measured in millimoles per liter (mmol/L).
• Mean Change From Baseline in Phosphate [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Phosphate was measured in millimoles per liter (mmol/L).
• Mean Change From Baseline in Cholesterol [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Cholesterol was measured in millimoles per liter (mmol/L).
• Mean Change From Baseline in Triglycerides [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Triglycerides was measured in millimoles per liter (mmol/L).
• Mean Change From Baseline in Protein [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Protein was measured in grams per liter (g/L).
• Mean Change From Baseline in Albumin [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Albumin was measured in grams per liter (g/L).
• Mean Change From Baseline in Glucose [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Glucose was measured in millimoles per liter (mmol/L).
• Mean Change From Baseline in Lipase, Pancreatic [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Lipase, Pancreatic was measured in units per liter (U/L).
• Mean Change From Baseline in Creatine Kinase [ Time Frame: From Baseline (Week 1) to Week 48 ]
  Creatine Kinase was measured in units per liter (U/L).
• Mean Change From Baseline in pH [ Time Frame: From Baseline (Week 1) to Week 48 ]
• Mean Change From Baseline in Erythrocytes (/HPF) [ Time Frame: From Baseline (Week 1) to Week 48 ]
• Mean Change From Baseline in Leukocytes (/HPF) [ Time Frame: From Baseline (Week 1) to Week 48 ]

• Original Secondary Outcome Measures (submitted: June 14, 2016): The percentage of subjects with BICLA response in the individual dose groups at Week 24 [ Time Frame: Week 24 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2 Efficacy and Safety Study of Dapirolizumab Pegol (DZP) in Systemic Lupus Erythematosus
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus (SLE)

Intervention

• Drug: Placebo
  Solution for infusion, 0,9% saline
• Drug: Dapirolizumab pegol (DZP)
  Solution for infusion

Study Arms

• Placebo Comparator: Placebo
  Placebo in a specified sequence for a total of 24 weeks
  Intervention: Drug: Placebo
• Experimental: DZP dose 1
  Dapirolizumab pegol (DZP) dose 1 in a specified sequence for a total of 24 weeks
  Intervention: Drug: Dapirolizumab pegol (DZP)
• Experimental: DZP dose 2
  Dapirolizumab pegol (DZP) dose 2 in a specified sequence for a total of 24 weeks
  Intervention: Drug: Dapirolizumab pegol (DZP)
• Experimental: DZP dose 3
  Dapirolizumab pegol (DZP) dose 3 in a specified sequence for a total of 24 weeks
  Intervention: Drug: Dapirolizumab pegol (DZP)

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 15, 2017): 182
• Original Estimated Enrollment (submitted: June 14, 2016): 160
• Actual Study Completion Date: November 19, 2018
• Actual Primary Completion Date: May 31, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Chile, Colombia, Germany, Hungary, Mexico, Peru, Poland, Romania, Russian Federation, Spain, Ukraine, United States

Administrative Information

• NCT Number: NCT02804763
• Other Study ID Numbers: SL0023; 2015-004457-40 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: UCB Pharma ( UCB Biopharma S.P.R.L. )
• Original Responsible Party: Same as current
• Current Study Sponsor: UCB Biopharma S.P.R.L.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; +1 844 599 2273 (UCB)

• PRS Account: UCB Pharma
• Verification Date: June 2021