NCT01135459

A Study to Evaluate the Efficacy and Safety of CEP-33457 in Participants With Systemic Lupus Erythematosus (SLE)

Completed Phase 2 Results posted Last updated 16 December 2022

What this trial tests

Phase 2 trial testing CEP-33457 in Systemic Lupus Erythematosus in 183 participants. Completed in 30 June 2012.

Timeline

24 June 2010

Primary endpoint
31 January 2012

30 June 2012

Quick facts

Lead sponsor	Cephalon, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	183
Start date	24 June 2010
Primary completion	31 January 2012
Estimated completion	30 June 2012
Sites	86 locations across France, Ukraine, Belgium, United Kingdom, Germany, Hungary, Poland, Portugal

Drugs / interventions tested

• CEP-33457 — full drug profile →
• Placebo

Conditions studied

• Systemic Lupus Erythematosus — all drugs for Systemic Lupus Erythematosus →

Sponsor

Cephalon, Inc. — full company profile →

Who can join

Adults 18 to 70, any sex, with Systemic Lupus Erythematosus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Achieving a Combined Clinical Response Using the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24 Primary · Week 24

An SRI response was defined as a reduction from baseline in SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥4 points, no worsening in Physician Global Assessment (PhGA), no new British Isles Lupus Assessment Group (BILAG) A body system score, and ≤1 new BILAG B body system score from baseline. SLEDAI-2K includes 24 weighted clinical and laboratory variables. Total score = 0 to 105. A score of 6 to 10 = moderate disease activity, and a reduction of \>3 points = improvement. PhGA was completed by physician using a visual analog scale (VAS) from 0=none to 3=severe. A change of \>0.3 points

Group	Value	95% CI
Placebo	37
CEP-33457	31

Number of Participants Achieving an SRI Response at Each Visit During the Treatment Period Secondary · Weeks 4, 8, 12, 16, and 20

An SRI response was defined as a reduction from baseline in SLEDAI-2K score of ≥4 points, no worsening in PhGA, no new BILAG A body system score, and ≤1 new BILAG B body system score from baseline. SLEDAI-2K includes 24 weighted clinical and laboratory variables. Total score = 0 to 105. A score of 6 to 10 = moderate disease activity, and a reduction of \>3 points = improvement. PhGA was completed by physician using a VAS from 0=none to 3=severe. A change of \>0.3 points = worsening. BILAG includes 97 clinical and laboratory items. Each organ system is assigned a score displayed as a grade from

Week 4

Group	Value	95% CI
Placebo	11
CEP-33457	13

Week 8

Group	Value	95% CI
Placebo	19
CEP-33457	27

Week 12

Group	Value	95% CI
Placebo	33
CEP-33457	29

Week 16

Group	Value	95% CI
Placebo	29
CEP-33457	28

Week 20

Group	Value	95% CI
Placebo	38
CEP-33457	30

Number of Participants Achieving a Reduction of at Least 4 Points in the SLEDAI-2K Total Score Secondary · Week 24

The SLEDAI-2K is a global index and includes 24 weighted clinical and laboratory variables. The total score (sum of all 24 scores) ranges from 0 to 105. A SLEDAI-2K score of 6 to 10 is indicative of moderate disease activity, and improvement is defined as a reduction of more than 3 points.

Group	Value	95% CI
Placebo	40
CEP-33457	32

Number of Participants Achieving a British Isles Lupus Assessment Group (BILAG) 2004 Response Secondary · Weeks 4, 8, 12, 16, 20, and 24

The BILAG 2004 is a validated objective and subjective global measure of the disease activity of SLE based on the physician intention to treat. It includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems; each organ system is assigned a score displayed as a grade from A to E, as follows: A=very active disease; B=participant needs increase in treatment for moderately active disease; C=stable or mild disease; D=previous organ involvement but no current disease activity; and E=no current disease activity and the organ system has never been involved. BILAG 2004

Week 4

Group	Value	95% CI
Placebo	86
CEP-33457	82

Week 8

Group	Value	95% CI
Placebo	82
CEP-33457	79

Week 12

Group	Value	95% CI
Placebo	80
CEP-33457	75

Week 16

Group	Value	95% CI
Placebo	76
CEP-33457	66

Week 20

Group	Value	95% CI
Placebo	74
CEP-33457	66

Week 24

Group	Value	95% CI
Placebo	70
CEP-33457	63

Number of Participants Achieving a BILAG 2004 Clinical Response Secondary · Weeks 4, 8, 12, 16, 20, and 24

The BILAG 2004 is a validated objective and subjective global measure of the disease activity of SLE based on the physician intention to treat. It includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems; each organ system is assigned a score displayed as a grade from A to E, as follows: A=very active disease; B=participant needs increase in treatment for moderately active disease; C=stable or mild disease; D=previous organ involvement but no current disease activity; and E=no current disease activity and the organ system has never been involved. BILAG 2004

Week 4

Group	Value	95% CI
Placebo	32
CEP-33457	36

Week 8

Group	Value	95% CI
Placebo	34
CEP-33457	37

Week 12

Group	Value	95% CI
Placebo	45
CEP-33457	34

Week 16

Group	Value	95% CI
Placebo	42
CEP-33457	33

Week 20

Group	Value	95% CI
Placebo	43
CEP-33457	32

Week 24

Group	Value	95% CI
Placebo	39
CEP-33457	31

Number of Participants Achieving a Physician Global Assessment (PhGA) Response Secondary · Weeks 4, 8, 12, 16, 20, and 24

The PhGA was completed by the physician using a 3 inch VAS labeled from 0=none to 3=severe. The PhGA response was defined as having no worsening in PhGA (with worsening defined as an increase in PhGA of more than 0.30 inch from baseline).

Week 4

Group	Value	95% CI
Placebo	80
CEP-33457	76

Week 8

Group	Value	95% CI
Placebo	83
CEP-33457	75

Week 12

Group	Value	95% CI
Placebo	77
CEP-33457	68

Week 16

Group	Value	95% CI
Placebo	71
CEP-33457	61

Week 20

Group	Value	95% CI
Placebo	73
CEP-33457	64

Week 24

Group	Value	95% CI
Placebo	71
CEP-33457	67

Number of Participants Achieving a Patient's Global Assessment (PtGA) Response Secondary · Weeks 4, 8, 12, 16, 20, and 24

The PhGA was completed by the participant using a 3 inch VAS labeled from 0=none to 3=severe. The PtGA response was defined as having no worsening in PtGA (with worsening defined as an increase in PtGA of more than 0.30 inch from baseline).

Week 4

Group	Value	95% CI
Placebo	79
CEP-33457	65

Week 8

Group	Value	95% CI
Placebo	73
CEP-33457	67

Week 12

Group	Value	95% CI
Placebo	64
CEP-33457	63

Week 16

Group	Value	95% CI
Placebo	65
CEP-33457	57

Week 20

Group	Value	95% CI
Placebo	65
CEP-33457	59

Week 24

Group	Value	95% CI
Placebo	63
CEP-33457	59

Change From Baseline in the Medical Outcome Survey Short-Form 36 (SF-36) Patient-Reported Questionnaire For Physical Component Summary (PCS) Score at Weeks 12 and 24 Secondary · Baseline, Week 12, Week 24

The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Items 1 to 4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item were summed and averaged (range: 0=worst to 100=best)

Baseline

Group	Value	95% CI
Placebo	37.3	± 9.60
CEP-33457	36.1	± 10.06

Change at Week 12

Group	Value	95% CI
Placebo	2.5	± 6.69
CEP-33457	2.2	± 6.70

Change at Week 24

Group	Value	95% CI
Placebo	2.1	± 7.66
CEP-33457	2.4	± 8.36

Change From Baseline in the Medical Outcome Survey SF-36 Patient-Reported Questionnaire For Mental Component Summary (MCS) Score at Weeks 12 and 24 Secondary · Baseline, Week 12, Week 24

The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Items 1 to 4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item were summed and averaged (range: 0=worst to 100=best)

Baseline

Group	Value	95% CI
Placebo	40.6	± 12.99
CEP-33457	41.7	± 12.26

Change at Week 12

Group	Value	95% CI
Placebo	0.5	± 11.10
CEP-33457	1.0	± 9.66

Change at Week 24

Group	Value	95% CI
Placebo	0.4	± 10.45
CEP-33457	1.7	± 10.81

Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Secondary · Baseline, Week 24

SLICC/ACR score or damage index is a measure of cumulative damage due to SLE. Damage is defined as nonreversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. Damage is defined for 12 separate organ systems: ocular (range 0-2), neuropsychiatric (0-6), renal (0-3), pulmonary (0-5), cardiovascular (0-6), peripheral vascular (0-5), gastrointestinal (0-6), musculoskeletal (0-7), skin (0-3), endocrine (diabetes) (0-1), gonadal (0-1) and malignancies (0-2). A score of 0=no damage, early damage is defi

Baseline

Group	Value	95% CI
Placebo	0.7	± 1.30
CEP-33457	0.6	± 1.08

Change at Week 24

Group	Value	95% CI
Placebo	-0.1	± 0.47
CEP-33457	-0.1	± 0.37

Number of Participants With Adverse Events (AEs) Secondary · Baseline up to Week 24

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located

Group	Value	95% CI
Placebo	81
CEP-33457	77

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 24. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 13/92 (14%)

Deaths: 0/92

CEP-33457

Serious: 9/91 (10%)

Deaths: 0/91

Serious adverse events (29 terms)

Reaction	System	Placebo	CEP-33457
Convulsion	Nervous system disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Haemolytic anaemia	Blood and lymphatic system disorders	—	—
Vertigo	Ear and labyrinth disorders	—	—
Goitre	Endocrine disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Medical device complication	General disorders	—	—
Drug hypersensitivity	Immune system disorders	—	—
Bronchitis	Infections and infestations	—	—
Cellulitis	Infections and infestations	—	—
Gastroenteritis viral	Infections and infestations	—	—
Staphylococcal sepsis	Infections and infestations	—	—
Lower limb fracture	Injury, poisoning and procedural complications	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Myositis	Musculoskeletal and connective tissue disorders	—	—
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	—	—
Cognitive disorder	Nervous system disorders	—	—
Encephalopathy	Nervous system disorders	—	—
Ischaemic stroke	Nervous system disorders	—	—
Paraesthesia	Nervous system disorders	—	—
Polyneuropathy	Nervous system disorders	—	—
Syncope	Nervous system disorders	—	—
Lupus nephritis	Renal and urinary disorders	—	—

Other adverse events (20 terms — click to expand)

Reaction	System	Placebo	CEP-33457
Arthritis	Musculoskeletal and connective tissue disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Systemic lupus erythematosus rash	Skin and subcutaneous tissue disorders	—	—
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Headache	Nervous system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Injection site erythema	General disorders	—	—
Pyrexia	General disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Weight decreased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: Convulsion, Anaemia, Haemolytic anaemia, Vertigo, Goitre, Diarrhoea, Nausea, Vomiting.

Data from ClinicalTrials.gov NCT01135459 adverse events section.

Sponsor's own description

The primary objective of this study is to evaluate the efficacy of a 200 micrograms (mcg) dose of CEP-33457 compared with placebo in participants with active systemic lupus erythematosus (SLE) as assessed by the proportion of participants achieving a combined clinical response using the SLE responder index (SRI) at Week 24.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Modulation of the immunity and inflammation by autophagy.
   Gan T, Qu S, Zhang H, Zhou XJ. · · 2023 · cited 27× · PMID 37405276 · DOI 10.1002/mco2.311
2. Interventions for cutaneous disease in systemic lupus erythematosus.
   Hannon CW, McCourt C, Lima HC, Chen S, et al · · 2021 · cited 26× · PMID 33687069 · DOI 10.1002/14651858.cd007478.pub2
3. Advances in drug therapy for systemic lupus erythematosus.
   Wallace DJ. · · 2010 · cited 23× · PMID 21114845 · DOI 10.1186/1741-7015-8-77