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A Study of the Effect of XmAb®5871 in Patients With Systemic Lupus Erythematosus

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ClinicalTrials.gov Identifier: NCT02725515
Recruitment Status : Completed
First Posted : April 1, 2016
Results First Posted : August 9, 2019
Last Update Posted : August 9, 2019
Sponsor:
Collaborators:
PPD
ICON plc
Information provided by (Responsible Party):
Xencor, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Systemic Lupus Erythematosus
Interventions Biological: XmAb5871
Biological: Placebo to match XmAb5871
Enrollment 105
Recruitment Details First informed consent date: 16FEB2016 First randomization date: 07MAR2016 Last informed consent date: 09NOV2017 Last randomization date: 07DEC2017
Pre-assignment Details After obtaining informed consent, IM depomedrol was administered and screening studies were performed over the 2-4 week screening period. Immunosuppressive therapy must have been stopped or tapered off by randomization on Day 1. Patients who did not meet the disease activity improvement criteria during the screening period were not randomized.
Arm/Group Title XmAb5871 Placebo
Hide Arm/Group Description XmAb5871 administered by IV infusion for up to a total of 16 infusions Placebo to match XmA5871 administered by IV infusion for up to a total of 16 infusions
Period Title: Overall Study
Started 53 52
Completed 28 17
Not Completed 25 35
Reason Not Completed
Refused infusion (no study treatment)             1             0
Loss of Improvement per Protocol             14             25
Withdrawal by Subject             2             1
Non-Compliance With Study Drug             0             3
Lost to Follow-up             1             1
Adverse Event             7             2
No Documented Disease Improvement             0             1
Completed Study Under Original Protocol             0             1
Lack of Response             0             1
Arm/Group Title XmAb5871 Placebo Total
Hide Arm/Group Description XmAb5871 administered by IV infusion for up to a total of 16 infusions Placebo to match XmA5871 administered by IV infusion for up to a total of 16 infusions Total of all reporting groups
Overall Number of Baseline Participants 52 52 104
Hide Baseline Analysis Population Description
Intent to Treat (ITT) Population: All patients who have received at least a partial dose of XmAb5871 or placebo. One patient was randomized to XmAb5871 but was never treated and withdrew from the study. This one patient is excluded from this analysis.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 52 participants 52 participants 104 participants
45.5
(23 to 65)
43.5
(20 to 64)
45.0
(20 to 65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 52 participants 104 participants
Female
50
  96.2%
49
  94.2%
99
  95.2%
Male
2
   3.8%
3
   5.8%
5
   4.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 52 participants 104 participants
Hispanic or Latino
6
  11.5%
4
   7.7%
10
   9.6%
Not Hispanic or Latino
46
  88.5%
48
  92.3%
94
  90.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 52 participants 104 participants
American Indian or Alaska Native
2
   3.8%
1
   1.9%
3
   2.9%
Asian
2
   3.8%
1
   1.9%
3
   2.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
26
  50.0%
25
  48.1%
51
  49.0%
White
19
  36.5%
25
  48.1%
44
  42.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   5.8%
0
   0.0%
3
   2.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 52 participants 52 participants 104 participants
52 52 104
SLEDAI Total Score at Screening--Efficacy Evaluable Population   [1] [2] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 50 participants 42 participants 92 participants
8.0
(4 to 16)
10.0
(2 to 18)
10.0
(2 to 18)
[1]
Measure Description: The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score ranges between 0 and 105. The higher the score, the more significant is the degree of disease activity. Scores of 6 and above are considered to be consistent with active disease requiring therapy.
[2]
Measure Analysis Population Description:

Efficacy Evaluable Population: All patients who:

  • Complete study through Day 225 assessments
  • Discontinue due to reaching the protocol specified LOI endpoint (and have not missed 2 or more consecutive doses prior to the LOI visit)
  • Discontinue due to drug-related adverse event (nonresponder)
1.Primary Outcome
Title Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 225
Time Frame Day 225
Hide Outcome Measure Data
Hide Analysis Population Description

Efficacy Evaluable Population: All patients who:

  • Complete study through Day 225 assessments
  • Discontinue due to reaching the protocol specified LOI endpoint (and have not missed 2 or more consecutive doses prior to the LOI visit)
  • Discontinue due to drug-related adverse event (nonresponder)
Arm/Group Title XmAb5871 Placebo
Hide Arm/Group Description:
XmAb5871 administered by IV infusion for up to a total of 16 infusions
Placebo to match XmA5871 administered by IV infusion for up to a total of 16 infusions
Overall Number of Participants Analyzed 50 42
Measure Type: Count of Participants
Unit of Measure: Participants
21
  42.0%
12
  28.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection XmAb5871, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1830
Comments [Not Specified]
Method Barnard's Unconditional Exact Test P-val
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 13.4
Confidence Interval (2-Sided) 95%
-6.6 to 32.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Patients Without Loss of Systemic Lupus Erythematosus Disease Activity Improvement on Day 169
Time Frame Day 169
Hide Outcome Measure Data
Hide Analysis Population Description

Efficacy Evaluable Population: All patients who:

  • Complete study through Day 225 assessments
  • Discontinue due to reaching the protocol specified LOI endpoint (and have not missed 2 or more consecutive doses prior to the LOI visit)
  • Discontinue due to drug-related adverse event (nonresponder)
Arm/Group Title XmAb5871 Placebo
Hide Arm/Group Description:
XmAb5871 administered by IV infusion for up to a total of 16 infusions
Placebo to match XmA5871 administered by IV infusion for up to a total of 16 infusions
Overall Number of Participants Analyzed 50 42
Measure Type: Count of Participants
Unit of Measure: Participants
29
  58.0%
17
  40.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection XmAb5871, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1075
Comments [Not Specified]
Method Barnard's Unconditional Exact Test P-val
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 17.5
Confidence Interval (2-Sided) 95%
-3.7 to 37.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Loss of Systemic Lupus Erythematosus Disease Activity Improvement Achieved by a Short Period of IM Steroid Therapy in SLE Patients
Hide Description

Loss of improvement was defined as worsening of disease activity that in the opinion of the principal investigator requires a change in treatment (exclusive of a decrease in oral steroids) AND one of:

  1. SELENA- SLEDAI increase of >=4 points from maximal improvement OR
  2. Worsening of at least 1 BILAG A or B score OR
  3. New BILAG A or B score.
Time Frame From the date of randomization until the date of loss of Systemic Lupus Erythematosus Disease Activity Improvement, or the date of the final efficacy assessment, up to 239 days.
Hide Outcome Measure Data
Hide Analysis Population Description

Efficacy Evaluable Population: All patients who:

  • Complete study through Day 225 assessments
  • Discontinue due to reaching the protocol specified LOI endpoint (and have not missed 2 or more consecutive doses prior to the LOI visit)
  • Discontinue due to drug-related adverse event (nonresponder)
Arm/Group Title XmAb5871 Placebo
Hide Arm/Group Description:
XmAb5871 administered by IV infusion for up to a total of 16 infusions
Placebo to match XmA5871 administered by IV infusion for up to a total of 16 infusions
Overall Number of Participants Analyzed 50 42
Median (95% Confidence Interval)
Unit of Measure: days
230
(197.0 to 239.0)
131
(85.0 to 225.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection XmAb5871, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0252
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.30 to 0.92
Estimation Comments [Not Specified]
Time Frame Adverse event summaries include events reported between randomization and the end of study visit (Day 253)
Adverse Event Reporting Description

Adverse events were reported by study center investigators using an electronic data capture system.

Safety Population: All patients who have received at least a partial dose of XmAb5871 or placebo.

One patient was randomized to XmAb5871 but was never treated and withdrew from the study. This one patient is excluded from adverse event summaries.

 
Arm/Group Title XmAb5871 Placebo
Hide Arm/Group Description XmAb5871 administered by IV infusion for up to a total of 16 infusions Placebo to match XmA5871 administered by IV infusion for up to a total of 16 infusions
All-Cause Mortality
XmAb5871 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/52 (0.00%)   0/52 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
XmAb5871 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   7/52 (13.46%)   4/52 (7.69%) 
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  1/52 (1.92%)  0/52 (0.00%) 
Anaemia  1  0/52 (0.00%)  1/52 (1.92%) 
Cardiac disorders     
Atrial fibrillation  1  1/52 (1.92%)  0/52 (0.00%) 
Gastrointestinal disorders     
Enteritis  1  0/52 (0.00%)  1/52 (1.92%) 
General disorders     
Pyrexia  1  1/52 (1.92%)  0/52 (0.00%) 
Infections and infestations     
Pneumonia  1  1/52 (1.92%)  0/52 (0.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  1/52 (1.92%)  0/52 (0.00%) 
Musculoskeletal and connective tissue disorders     
Systemic lupus erythematosus  1  1/52 (1.92%)  1/52 (1.92%) 
Nervous system disorders     
Migraine  1  0/52 (0.00%)  1/52 (1.92%) 
Dizziness  1  1/52 (1.92%)  0/52 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  0/52 (0.00%)  1/52 (1.92%) 
Vascular disorders     
Hypertension  1  1/52 (1.92%)  0/52 (0.00%) 
1
Term from vocabulary, MedDRA version 21.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
XmAb5871 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   41/52 (78.85%)   28/52 (53.85%) 
Cardiac disorders     
Tachycardia  1  3/52 (5.77%)  0/52 (0.00%) 
Gastrointestinal disorders     
Nausea  1  20/52 (38.46%)  9/52 (17.31%) 
Vomiting  1  9/52 (17.31%)  1/52 (1.92%) 
Diarrhoea  1  4/52 (7.69%)  4/52 (7.69%) 
Abdominal pain  1  5/52 (9.62%)  1/52 (1.92%) 
Abdominal pain upper  1  3/52 (5.77%)  2/52 (3.85%) 
General disorders     
Peripheral swelling  1  3/52 (5.77%)  2/52 (3.85%) 
Fatigue  1  4/52 (7.69%)  0/52 (0.00%) 
Non-cardiac chest pain  1  4/52 (7.69%)  0/52 (0.00%) 
Infections and infestations     
Upper respiratory tract infection  1  4/52 (7.69%)  6/52 (11.54%) 
Urinary tract infection  1  5/52 (9.62%)  3/52 (5.77%) 
Nasopharyngitis  1  4/52 (7.69%)  3/52 (5.77%) 
Acute sinusitis  1  3/52 (5.77%)  2/52 (3.85%) 
Bronchitis  1  2/52 (3.85%)  3/52 (5.77%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  3/52 (5.77%)  2/52 (3.85%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  5/52 (9.62%)  6/52 (11.54%) 
Back pain  1  8/52 (15.38%)  2/52 (3.85%) 
Pain in extremity  1  6/52 (11.54%)  1/52 (1.92%) 
Arthralgia  1  2/52 (3.85%)  3/52 (5.77%) 
Nervous system disorders     
Headache  1  12/52 (23.08%)  1/52 (1.92%) 
Dizziness  1  8/52 (15.38%)  1/52 (1.92%) 
Migraine  1  3/52 (5.77%)  0/52 (0.00%) 
Psychiatric disorders     
Anxiety  1  3/52 (5.77%)  1/52 (1.92%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/52 (7.69%)  4/52 (7.69%) 
Oropharyngeal pain  1  3/52 (5.77%)  1/52 (1.92%) 
Sinus congestion  1  3/52 (5.77%)  0/52 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/52 (1.92%)  3/52 (5.77%) 
Vascular disorders     
Flushing  1  7/52 (13.46%)  0/52 (0.00%) 
Hot flush  1  4/52 (7.69%)  1/52 (1.92%) 
1
Term from vocabulary, MedDRA version 21.0
Indicates events were collected by systematic assessment
Prior to database lock, an evaluation of early discontinuation rates indicated that the efficacy-evaluable population might be insufficient to power the primary analysis. An additional 15 patients were enrolled beyond the originally planned 90.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Vice President, Biometrics
Organization: Xencor, Inc.
Phone: 858-480-3414
EMail: bburington@xencor.com
Layout table for additonal information
Responsible Party: Xencor, Inc.
ClinicalTrials.gov Identifier: NCT02725515     History of Changes
Other Study ID Numbers: XmAb5871-04
First Submitted: January 8, 2016
First Posted: April 1, 2016
Results First Submitted: June 6, 2019
Results First Posted: August 9, 2019
Last Update Posted: August 9, 2019