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. )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus (SLE)	Drug: Placebo; Drug: Dapirolizumab pegol (DZP)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 2, 2016
• Actual Primary Completion Date: May 31, 2018
• Actual Study Completion Date: November 19, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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).
7. 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).
8. 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).
9. Mean Change From Baseline in Temperature [ Time Frame: From Baseline (Week 1) to Week 48 ]
   Temperature was measured in Grad Celsius (°C).
10. 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).
11. Mean Change From Baseline in Height [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Height was measured in centimeters (cm).
12. 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).
13. Mean Change From Baseline in Hemoglobin [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Hemoglobin was measured in grams per liter (g/L).
14. 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.
15. 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).
16. 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).
17. 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).
18. 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).
19. 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).
20. 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).
21. Mean Change From Baseline in Basophils/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Basophils/Leukocytes was measured in percentages (%).
22. 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).
23. Mean Change From Baseline in Eosinophils/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Eosinophils/Leukocytes was measured in percentages (%).
24. 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).
25. Mean Change From Baseline in Lymphocytes/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Lymphocytes/Leukocytes was measured in percentages (%).
26. 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).
27. Mean Change From Baseline in Monocytes/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Monocytes/Leukocytes was measured in percentages (%).
28. 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).
29. Mean Change From Baseline in Neutrophils/Leukocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Neutrophils/Leukocytes was measured in percentages (%).
30. 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).
31. 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).
32. Mean Change From Baseline in CD3/Lymphocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
    CD3/Lymphocytes was measured in percentages (%).
33. 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).
34. Mean Change From Baseline in CD19/Lymphocytes [ Time Frame: From Baseline (Week 1) to Week 48 ]
    CD19/Lymphocytes was measured in percentages (%).
35. 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).
36. 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).
37. 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).
38. 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).
39. Mean Change From Baseline in Bilirubin [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Bilirubin was measured in micromols per liter (µmol/L).
40. 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).
41. 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).
42. Mean Change From Baseline in Creatinine [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Creatinine was measured in micromols per liter (µmol/L).
43. 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).
44. Mean Change From Baseline in Sodium [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Sodium was measured in millimoles per liter (mmol/L).
45. Mean Change From Baseline in Potassium [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Potassium was measured in millimoles per liter (mmol/L).
46. Mean Change From Baseline in Calcium [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Calcium was measured in millimoles per liter (mmol/L).
47. Mean Change From Baseline in Phosphate [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Phosphate was measured in millimoles per liter (mmol/L).
48. Mean Change From Baseline in Cholesterol [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Cholesterol was measured in millimoles per liter (mmol/L).
49. Mean Change From Baseline in Triglycerides [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Triglycerides was measured in millimoles per liter (mmol/L).
50. Mean Change From Baseline in Protein [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Protein was measured in grams per liter (g/L).
51. Mean Change From Baseline in Albumin [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Albumin was measured in grams per liter (g/L).
52. Mean Change From Baseline in Glucose [ Time Frame: From Baseline (Week 1) to Week 48 ]
    Glucose was measured in millimoles per liter (mmol/L).
53. 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).
54. 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).
55. Mean Change From Baseline in pH [ Time Frame: From Baseline (Week 1) to Week 48 ]
56. Mean Change From Baseline in Erythrocytes (/HPF) [ Time Frame: From Baseline (Week 1) to Week 48 ]
57. Mean Change From Baseline in Leukocytes (/HPF) [ Time Frame: From Baseline (Week 1) to Week 48 ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Alabama

Sl0023 312

Birmingham, Alabama, United States, 35294

United States, California

Sl0023 307

El Cajon, California, United States, 92020

Sl0023 309

El Cajon, California, United States, 92020

Sl0023 323

Huntington Beach, California, United States, 92646

Sl0023 311

Los Angeles, California, United States, 90048

Sl0023 314

Thousand Oaks, California, United States, 91360

Sl0023 302

Upland, California, United States, 91786

United States, Connecticut

Sl0023 326

New Haven, Connecticut, United States, 06520

United States, Florida

Sl0023 304

Clearwater, Florida, United States, 33765

Sl0023 322

DeBary, Florida, United States, 32713

Sl0023 301

Miami Lakes, Florida, United States, 33014

Sl0023 321

Miami, Florida, United States, 33136

Sl0023 319

Palm Harbor, Florida, United States, 34684

Sl0023 310

Tampa, Florida, United States, 33603

United States, Georgia

Sl0023 324

Atlanta, Georgia, United States, 30303

Sl0023 327

Stockbridge, Georgia, United States, 30281

United States, Idaho

Sl0023 320

Idaho Falls, Idaho, United States, 83404

United States, New Mexico

Sl0023 306

Albuquerque, New Mexico, United States, 87104

United States, New York

Sl0023 313

Lake Success, New York, United States, 11042

United States, Oklahoma

Sl0023 305

Oklahoma City, Oklahoma, United States, 73101

United States, Tennessee

Sl0023 315

Jackson, Tennessee, United States, 38305

Sl0023 308

Memphis, Tennessee, United States, 38119

United States, Texas

Sl0023 317

Amarillo, Texas, United States, 79124

Sl0023 303

Houston, Texas, United States, 77034

United States, Washington

Sl0023 328

Spokane, Washington, United States, 99204

Bulgaria

Sl0023 101

Plovdiv, Bulgaria

Sl0023 102

Plovdiv, Bulgaria

Chile

Sl0023 202

Providencia, Chile

Sl0023 203

Providencia, Chile

Sl0023 201

Puerto Varas, Chile

Sl0023 204

Vina del Mar, Chile

Colombia

Sl0023 213

Barranquilla, Colombia

Sl0023 212

Bogotá, Colombia

Sl0023 214

Bogotá, Colombia

Sl0023 216

Bucaramanga, Colombia

Sl0023 211

Chía, Colombia

Sl0023 215

Medellín, Colombia

Germany

Sl0023 341

Hannover, Germany

Sl0023 113

Leipzig, Germany

Hungary

Sl0023 124

Debrecen, Hungary

Mexico

Sl0023 225

Guadalajara, Mexico

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León, Mexico

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Mexico, Mexico

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San Luis Potosí, Mexico

Peru

Sl0023 232

Arequipa, Peru

Sl0023 231

Lima, Peru

Sl0023 234

Lima, Peru

Sl0023 235

Lima, Peru

Poland

Sl0023 133

Bytom, Poland

Sl0023 136

Lublin, Poland

Sl0023 131

Poznan, Poland

Sl0023 134

Sosnowiec, Poland

Sl0023 135

Warszawa, Poland

Sl0023 138

Łódź, Poland

Romania

Sl0023 146

Brasov, Romania

Sl0023 142

Bucuresti, Romania

Sl0023 144

Cluj-Napoca, Romania

Sl0023 141

Galati, Romania

Russian Federation

Sl0023 157

Kazan, Russian Federation

Sl0023 156

Kemerovo, Russian Federation

Sl0023 152

Saint Petersburg, Russian Federation

Sl0023 155

Voronezh, Russian Federation

Sl0023 151

Yaroslavl', Russian Federation

Sl0023 153

Yekaterinburg, Russian Federation

Spain

Sl0023 161

Barcelona, Spain

Sl0023 162

Madrid, Spain

Sl0023 166

Tenerife, Spain

Ukraine

Sl0023 172

Kyiv, Ukraine

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Kyiv, Ukraine

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Odessa, Ukraine

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Vinnytsya, Ukraine

Sponsors and Collaborators

UCB Biopharma S.P.R.L.

Investigators

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

  Study Documents (Full-Text)

Documents provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):

Study Protocol  [PDF] December 14, 2016

Statistical Analysis Plan  [PDF] September 4, 2018

More Information

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT02804763
• Other Study ID Numbers: SL0023; 2015-004457-40 ( EudraCT Number )
• First Posted: June 17, 2016
• Results First Posted: June 30, 2021
• Last Update Posted: June 30, 2021
• Last Verified: June 2021

Keywords provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):

Systemic Lupus Erythematosus (SLE); Dapirolizumab Pegol (DZP)

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases