Phase 2
N=312
A Phase II Study to Evaluate Safety and Efficacy of ALX-0061 in Subjects With Systemic Lupus Erythematosus
Lupus Erythematosus, Systemic
Bottom Line
View on ClinicalTrials.gov: NCT02437890 ↗Enrolled (actual)
312
Serious AEs
7.4%
Results posted
Feb 2019
Primary outcome: Primary: Number and Percentage of Subjects Who Achieved a Response at Week 24 According to the Modified British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (mBICLA) Score — 29; 28; 24; 24 Participants — p== 0.526
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ALX-0061 (Biological); Placebo (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ablynx, a Sanofi company
- Primary completion
- Jan 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number and Percentage of Subjects Who Achieved a Response at Week 24 According to the Modified British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (mBICLA) Score |
29; 28; 24; 24; 23 | = 0.526 |
| SECONDARY Number and Percentage of Subjects With mBICLA Response at Week 24 and Week 48 |
28; 28; 22; 24; 22; 28 | — |
| SECONDARY Number and Percentage of Subjects With Modified Systemic Lupus Erythematosus Responder Index (mSRI-4) Response at Week 24 and Week 48 |
37; 39; 30; 33; 29; 34 | — |
| SECONDARY Number and Percentage of Subjects With mSRI-5 Response at Week 24 and Week 48 |
17; 24; 19; 20; 16; 20 | — |
| SECONDARY Number and Percentage of Subjects With mSRI-6 Response at Week 24 and Week 48 |
16; 23; 19; 19; 15; 20 | — |
| SECONDARY Number and Percentage of Subjects With mSRI-7 Response at Week 24 and Week 48 |
9; 8; 8; 12; 7; 12 | — |
| SECONDARY Number and Percentage of Subjects With mSRI-8 Response at Week 24 and Week 48. |
9; 7; 8; 10; 7; 11 | — |
| SECONDARY Change From Baseline in Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (mSLEDAI-2K) Score at Week 24 and Week 48 |
-4.0; -4.6; -3.8; -4.3; -3.6; -4.5 | — |
| SECONDARY Number and Percentage of Subjects With BILAG-2004 Normal Improvement at Week 24 and Week 48 |
31; 29; 28; 25; 24; 34 | — |
| SECONDARY Number and Percentage of Subjects With BILAG-2004 Enhanced Improvement at Week 24 and Week 48 |
7; 16; 11; 6; 13; 5 | — |
| SECONDARY BILAG-2004 Total Score at Baseline, Week 24 and Week 48 |
17.4; 17.9; 15.2; 17.4; 17.3; 6.8 | — |
| SECONDARY Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Mucocutaneous System at Week 24 and Week 48 |
25; 24; 18; 21; 25; 26 | — |
| SECONDARY Number and Percentage of Subjects With BILAG-2004 Normal Improvement in Musculoskeletal System at Week 24 and Week 48 |
41; 39; 36; 36; 33; 40 | — |
| SECONDARY Number and Percentage of Subjects With Persistent Minimal or no Activity in 9 Organ Systems According to BILAG-2004 Systems Tally at Week 24 and Week 48 |
15; 24; 19; 16; 16; 20 | — |
| SECONDARY Change From Baseline in Physician's Global Assessment (PGA) at Week 24 and Week 48 |
-25.2; -28.4; -26.2; -23.5; -22.7; -28.3 | — |
| SECONDARY Change From Baseline in Patient's Global Assessment at Week 24 and Week 48 |
-12.4; -13.5; -14.9; -20.1; -16.0; -15.1 | — |
| SECONDARY Change From Baseline in Proteinuria at Week 24 and Week 48 |
6.17; 1.77; 1.03; -3.02; 0.16; 4.89 | — |
| SECONDARY Number of Subjects Who Were Treatment-emergent Urine Sediment Positive at Week 24 and Week 48 |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Change From Baseline in Serum Creatinine at Week 24 and Week 48 |
-1.25; -3.29; -1.50; -3.98; -0.86; 1.19 | — |
| SECONDARY Change From Baseline in Creatinine Clearance Estimation (eGFR) at Week 24 and Week 48 |
-1.63; 4.83; -1.72; -0.90; -8.91; -6.00 | — |
| SECONDARY Number of and Percentage Treatment Failures From Baseline to Week 24 and Week 48 |
2; 0; 4; 2; 3; 5 | — |
| SECONDARY Number and Percentage of Subjects Experiencing Severe Flares According to BILAG-2004 Flare Index From Baseline to Week 24 and Week 48 |
8; 6; 6; 7; 6; 8 | — |
| SECONDARY Number and Percentage of Subjects Experiencing Severe Flares According to mSLEDAI-2K Flare Index (mSFI) From Baseline to Week 24 and Week 48 |
1; 0; 2; 2; 1; 4 | — |
| SECONDARY Percent Change From Baseline in Daily Dose of Steroids at Week 24 and Week 48 |
3.87; -0.80; 0.25; -1.40; -3.46; 6.93 | — |
| SECONDARY Number and Percentage of Subjects Whose Daily Dose of Steroids Was Reduced Without Severe Flares During Weeks 40-48 |
3; 2; 5; 1; 3; 3 | — |
| SECONDARY Number and Percentage of Subjects Who Discontinued Prednisone (or Equivalent) by Week 48 Without Experiencing a Severe Flare |
0; 0; 1; 1; 0; 0 | — |
| SECONDARY Change From Baseline in Physical Component Scores of Short Form (36) Health Survey (SF-36) at Week 24 and Week 48 |
4.71; 4.56; 6.77; 4.67; 5.01; 3.73 | — |
| SECONDARY Change From Baseline in Mental Component Scores of SF-36 at Week 24 and Week 48 |
0.08; -0.99; -0.56; 0.45; -1.18; 1.50 | — |
| SECONDARY Change From Baseline in 28 Joint Count Swollenness (SJC28) Score at Week 24 and Week 48 |
-4.8; -5.0; -4.9; -4.8; -4.5; -5.0 | — |
| SECONDARY Change From Baseline in 28 Joint Count Tenderness (TJC28) Score at Week 24 and Week 48 |
-6.8; -6.8; -6.4; -5.8; -5.5; -6.6 | — |
| SECONDARY Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12, Week 24 and Week 48 |
-2.4; -1.9; -1.4; -1.6; -1.3; -1.1 | — |
| SECONDARY Change From Baseline in CLASI Damage Score at Week 12, Week 24 and Week 48 |
0.1; 0.1; -0.1; -0.3; -0.4; 0.4 | — |
| SECONDARY ALX-0061 Serum Concentrations at Week 24 and Week 48 |
0.118; 2.05; 18.1; 30.7; 0.155; 2.17 | — |
| SECONDARY Actual Values of Soluble Interleukin 6 Receptor (sIL-6R) Concentrations at Baseline, Week 24, and Week 48 |
42.22; 37.63; 38.10; 42.14; 36.92; 39.70 | — |
| SECONDARY Actual Values of C-reactive Protein (CRP) Concentrations at Baseline, Week 24, and Week 48 |
43.58; 49.05; 38.89; 66.32; 32.23; 59.43 | — |
| SECONDARY Actual Values of Fibrinogen Concentrations at Baseline, Week 24, and Week 48 |
3.2; 3.2; 3.2; 3.2; 3.1; 3.3 | — |
| SECONDARY Actual Values of Anti-double-stranded (ds) DNA Concentrations at Baseline, Week 24, and Week 48 |
132.90; 145.87; 52.88; 68.92; 73.34; 81.36 | — |
| SECONDARY Actual Values of Complement C3 Concentrations at Baseline, Week 24, and Week 48 |
102.3; 100.2; 101.9; 105.8; 98.6; 101.7 | — |
| SECONDARY Actual Values of Complement C4 Concentrations at Baseline, Week 24, and Week 48 |
17.3; 17.8; 15.9; 18.7; 16.3; 17.5 | — |
| SECONDARY Actual Values for Hemolytic Complement Component 50 (CH50) at Baseline, Week 24, and Week 48 |
101.1; 109.6; 98.9; 103.0; 82.4; 95.8 | — |
| SECONDARY Number and Percentage of Subjects Who Were Treatment-emergent (TE) Anti-drug Antibody (ADA) Positive |
32; 16; 18; 31; 38 | — |
Summary
Primary objective:
To assess the efficacy and safety of different dose regimens of ALX-0061 administered subcutaneously (s.c.) to subjects with moderate to severe active, seropositive systemic lupus erythematosus (SLE) compared to placebo.
Secondary objectives:
To assess the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, flare rate, steroid reduction and health-related quality of life, with different dose regimens of ALX-0061.
Eligibility Criteria
Inclusion Criteria
- Man or woman ≥ 18 years and < 65 years of age
- Have a diagnosis of SLE for at least 6 months prior to screening and fulfill the 1997 American College of Rheumatology (ACR) or 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria
- Have moderate to severe active SLE
- Have seropositive disease at screening
- Subject must be at least on one or more of the treatments for SLE as listed in the protocol
- Others as defined in the protocol
Exclusion Criteria
- Have an A score on the revised BILAG-2004 other than in the mucocutaneous and/or musculoskeletal system at screening and at baseline for the organ systems that can be clinically assessed
- Have a systemic inflammatory disease other than SLE
- Clinically significant infection treated or needing treatment
- Any active or recurrent viral infection that based on the Investigator´s clinical assessment makes the subject unsuitable for the study
- Have received prior therapy blocking the interleukin-6 (IL-6) pathway
- Others as defined in the protocol
Data sourced from ClinicalTrials.gov (NCT02437890). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.