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

Systemic Lupus Erythematosus (SLE) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02804763
• Other study ID #: SL0023
• Secondary ID: 2015-004457-40
• Status: Completed
• Phase: Phase 2
• Start date: June 2, 2016
• Est. completion date: November 19, 2018

Study information

• Verified date: June 2021
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 182
• Est. completion date: November 19, 2018
• Est. primary completion date: May 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus (SLE)

Intervention

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

Locations

Country	Name	City	State
Bulgaria	Sl0023 101	Plovdiv
Bulgaria	Sl0023 102	Plovdiv
Chile	Sl0023 202	Providencia
Chile	Sl0023 203	Providencia
Chile	Sl0023 201	Puerto Varas
Chile	Sl0023 204	Vina del Mar
Colombia	Sl0023 213	Barranquilla
Colombia	Sl0023 212	Bogotá
Colombia	Sl0023 214	Bogotá
Colombia	Sl0023 216	Bucaramanga
Colombia	Sl0023 211	Chía
Colombia	Sl0023 215	Medellín
Germany	Sl0023 341	Hannover
Germany	Sl0023 113	Leipzig
Hungary	Sl0023 124	Debrecen
Mexico	Sl0023 225	Guadalajara
Mexico	Sl0023 224	León
Mexico	Sl0023 221	Mexico
Mexico	Sl0023 222	San Luis Potosí
Peru	Sl0023 232	Arequipa
Peru	Sl0023 231	Lima
Peru	Sl0023 234	Lima
Peru	Sl0023 235	Lima
Poland	Sl0023 133	Bytom
Poland	Sl0023 138	Lódz
Poland	Sl0023 136	Lublin
Poland	Sl0023 131	Poznan
Poland	Sl0023 134	Sosnowiec
Poland	Sl0023 135	Warszawa
Romania	Sl0023 146	Brasov
Romania	Sl0023 142	Bucuresti
Romania	Sl0023 144	Cluj-Napoca
Romania	Sl0023 141	Galati
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
Spain	Sl0023 161	Barcelona
Spain	Sl0023 162	Madrid
Spain	Sl0023 166	Tenerife
Ukraine	Sl0023 172	Kyiv
Ukraine	Sl0023 175	Kyiv
Ukraine	Sl0023 171	Odessa
Ukraine	Sl0023 173	Vinnytsya
United States	Sl0023 306	Albuquerque	New Mexico
United States	Sl0023 317	Amarillo	Texas
United States	Sl0023 324	Atlanta	Georgia
United States	Sl0023 312	Birmingham	Alabama
United States	Sl0023 304	Clearwater	Florida
United States	Sl0023 322	DeBary	Florida
United States	Sl0023 307	El Cajon	California
United States	Sl0023 309	El Cajon	California
United States	Sl0023 303	Houston	Texas
United States	Sl0023 323	Huntington Beach	California
United States	Sl0023 320	Idaho Falls	Idaho
United States	Sl0023 315	Jackson	Tennessee
United States	Sl0023 313	Lake Success	New York
United States	Sl0023 311	Los Angeles	California
United States	Sl0023 308	Memphis	Tennessee
United States	Sl0023 321	Miami	Florida
United States	Sl0023 301	Miami Lakes	Florida
United States	Sl0023 326	New Haven	Connecticut
United States	Sl0023 305	Oklahoma City	Oklahoma
United States	Sl0023 319	Palm Harbor	Florida
United States	Sl0023 328	Spokane	Washington
United States	Sl0023 327	Stockbridge	Georgia
United States	Sl0023 310	Tampa	Florida
United States	Sl0023 314	Thousand Oaks	California
United States	Sl0023 302	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma S.P.R.L.

Countries where clinical trial is conducted

United States,  Bulgaria,  Chile,  Colombia,  Germany,  Hungary,  Mexico,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Mean Change From Baseline in Systolic Blood Pressure	Blood pressure was measured in millimetre of mercury (mmHg).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Diastolic Blood Pressure	Blood pressure was measured in millimetre of mercury (mmHg).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Pulse Rate	Pulse Rate was measured in beats per minute (beats/min).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Temperature	Temperature was measured in Grad Celsius (°C).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	Mean Change From Baseline in Height	Height was measured in centimeters (cm).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	Mean Change From Baseline in Hemoglobin	Hemoglobin was measured in grams per liter (g/L).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean Change From Baseline in Basophils/Leukocytes	Basophils/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	Mean Change From Baseline in Eosinophils/Leukocytes	Eosinophils/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	Mean Change From Baseline in Lymphocytes/Leukocytes	Lymphocytes/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	Mean Change From Baseline in Monocytes/Leukocytes	Monocytes/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	Mean Change From Baseline in Neutrophils/Leukocytes	Neutrophils/Leukocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	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
Secondary	Mean Change From Baseline in CD3/Lymphocytes	CD3/Lymphocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	Mean Change From Baseline in CD19/Lymphocytes	CD19/Lymphocytes was measured in percentages (%).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Aspartate Aminotransferase	Aspartate Aminotransferase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Alanine Aminotransferase	Alanine Aminotransferase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Alkaline Phosphatase	Alkaline Phosphatase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Secondary	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
Secondary	Mean Change From Baseline in Bilirubin	Bilirubin was measured in micromols per liter (µmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Direct Bilirubin	Direct Bilirubin was measured in micromols per liter (µmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Lactate Dehydrogenase	Lactate Dehydrogenase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Creatinine	Creatinine was measured in micromols per liter (µmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Urea Nitrogen	Urea Nitrogen was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Sodium	Sodium was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Potassium	Potassium was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Calcium	Calcium was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Phosphate	Phosphate was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Cholesterol	Cholesterol was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Triglycerides	Triglycerides was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Protein	Protein was measured in grams per liter (g/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Albumin	Albumin was measured in grams per liter (g/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Glucose	Glucose was measured in millimoles per liter (mmol/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Lipase, Pancreatic	Lipase, Pancreatic was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Creatine Kinase	Creatine Kinase was measured in units per liter (U/L).	From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in pH		From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Erythrocytes (/HPF)		From Baseline (Week 1) to Week 48
Secondary	Mean Change From Baseline in Leukocytes (/HPF)		From Baseline (Week 1) to Week 48