Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of CEP-33457 in Participants With Systemic Lupus Erythematosus (SLE) (NCT NCT01135459)

Last Updated: 2022-12-16

Results Overview

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 = worsening. BILAG includes 97 clinical and laboratory items. Each organ system is assigned a score displayed as a grade from A to E: A=very active disease; B=patient 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 organ system has never been involved.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

183 participants

Primary outcome timeframe

Week 24

Results posted on

2022-12-16

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to CEP-33457 subcutaneously (SC) every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 Participants received CEP-33457 200 micrograms (mcg) SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Overall Study STARTED	92	91
Overall Study Received at Least 1 Dose of Study Drug	92	91
Overall Study COMPLETED	71	71
Overall Study NOT COMPLETED	21	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to CEP-33457 subcutaneously (SC) every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 Participants received CEP-33457 200 micrograms (mcg) SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Overall Study Adverse Event	8	10
Overall Study Lack of Efficacy	3	1
Overall Study Withdrawal by Subject	2	3
Overall Study Protocol Violation	5	3
Overall Study Lost to Follow-up	2	1
Overall Study Non-compliance to study procedures	0	1
Overall Study Other than specified	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=91 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	Total n=183 Participants Total of all reporting groups
Age, Continuous	40.1 years STANDARD_DEVIATION 11.88 • n=5 Participants	42.0 years STANDARD_DEVIATION 11.25 • n=7 Participants	41.0 years STANDARD_DEVIATION 11.58 • n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	86 Participants n=7 Participants	169 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	82 Participants n=5 Participants	80 Participants n=7 Participants	162 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	64 Participants n=5 Participants	67 Participants n=7 Participants	131 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaskan Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=90 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Number of Participants Achieving a Combined Clinical Response Using the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24	37 Participants	31 Participants

SECONDARY outcome

Timeframe: 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 A to E: 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 organ system has never been involved.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=90 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Number of Participants Achieving an SRI Response at Each Visit During the Treatment Period Week 16	29 Participants	28 Participants
Number of Participants Achieving an SRI Response at Each Visit During the Treatment Period Week 4	11 Participants	13 Participants
Number of Participants Achieving an SRI Response at Each Visit During the Treatment Period Week 8	19 Participants	27 Participants
Number of Participants Achieving an SRI Response at Each Visit During the Treatment Period Week 12	33 Participants	29 Participants
Number of Participants Achieving an SRI Response at Each Visit During the Treatment Period Week 20	38 Participants	30 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=90 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Number of Participants Achieving a Reduction of at Least 4 Points in the SLEDAI-2K Total Score	40 Participants	32 Participants

SECONDARY outcome

Timeframe: 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 response was defined as no new A body system score and no more than 1 new BILAG B body system score from baseline.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=90 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Number of Participants Achieving a British Isles Lupus Assessment Group (BILAG) 2004 Response Week 12	80 Participants	75 Participants
Number of Participants Achieving a British Isles Lupus Assessment Group (BILAG) 2004 Response Week 16	76 Participants	66 Participants
Number of Participants Achieving a British Isles Lupus Assessment Group (BILAG) 2004 Response Week 20	74 Participants	66 Participants
Number of Participants Achieving a British Isles Lupus Assessment Group (BILAG) 2004 Response Week 4	86 Participants	82 Participants
Number of Participants Achieving a British Isles Lupus Assessment Group (BILAG) 2004 Response Week 8	82 Participants	79 Participants
Number of Participants Achieving a British Isles Lupus Assessment Group (BILAG) 2004 Response Week 24	70 Participants	63 Participants

SECONDARY outcome

Timeframe: 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 clinical response was defined as having an improvement in at least 1 category from a B score at baseline to a C or D score with no worsening in any other category from baseline.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=90 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Number of Participants Achieving a BILAG 2004 Clinical Response Week 12	45 Participants	34 Participants
Number of Participants Achieving a BILAG 2004 Clinical Response Week 16	42 Participants	33 Participants
Number of Participants Achieving a BILAG 2004 Clinical Response Week 24	39 Participants	31 Participants
Number of Participants Achieving a BILAG 2004 Clinical Response Week 20	43 Participants	32 Participants
Number of Participants Achieving a BILAG 2004 Clinical Response Week 4	32 Participants	36 Participants
Number of Participants Achieving a BILAG 2004 Clinical Response Week 8	34 Participants	37 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=90 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Number of Participants Achieving a Physician Global Assessment (PhGA) Response Week 4	80 Participants	76 Participants
Number of Participants Achieving a Physician Global Assessment (PhGA) Response Week 8	83 Participants	75 Participants
Number of Participants Achieving a Physician Global Assessment (PhGA) Response Week 12	77 Participants	68 Participants
Number of Participants Achieving a Physician Global Assessment (PhGA) Response Week 16	71 Participants	61 Participants
Number of Participants Achieving a Physician Global Assessment (PhGA) Response Week 20	73 Participants	64 Participants
Number of Participants Achieving a Physician Global Assessment (PhGA) Response Week 24	71 Participants	67 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=90 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Number of Participants Achieving a Patient's Global Assessment (PtGA) Response Week 4	79 Participants	65 Participants
Number of Participants Achieving a Patient's Global Assessment (PtGA) Response Week 8	73 Participants	67 Participants
Number of Participants Achieving a Patient's Global Assessment (PtGA) Response Week 12	64 Participants	63 Participants
Number of Participants Achieving a Patient's Global Assessment (PtGA) Response Week 16	65 Participants	57 Participants
Number of Participants Achieving a Patient's Global Assessment (PtGA) Response Week 20	65 Participants	59 Participants
Number of Participants Achieving a Patient's Global Assessment (PtGA) Response Week 24	63 Participants	59 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24

Population: Full analysis set included all randomized participants who took at least 1 dose of study drug and had the baseline SLEDAI-2K total score, BILAG 2004 body system scores, and the PhGA score. Overall number of participants analyzed = participants evaluable for this outcome measure. Number analyzed = participants evaluable at specified timepoint.

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). Higher scores represent better health status and functional ability.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=89 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
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 Baseline	37.3 units on a scale Standard Deviation 9.60	36.1 units on a scale Standard Deviation 10.06
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 Change at Week 12	2.5 units on a scale Standard Deviation 6.69	2.2 units on a scale Standard Deviation 6.70
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 Change at Week 24	2.1 units on a scale Standard Deviation 7.66	2.4 units on a scale Standard Deviation 8.36

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=89 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Change From Baseline in the Medical Outcome Survey SF-36 Patient-Reported Questionnaire For Mental Component Summary (MCS) Score at Weeks 12 and 24 Baseline	40.6 units on a scale Standard Deviation 12.99	41.7 units on a scale Standard Deviation 12.26
Change From Baseline in the Medical Outcome Survey SF-36 Patient-Reported Questionnaire For Mental Component Summary (MCS) Score at Weeks 12 and 24 Change at Week 12	0.5 units on a scale Standard Deviation 11.10	1.0 units on a scale Standard Deviation 9.66
Change From Baseline in the Medical Outcome Survey SF-36 Patient-Reported Questionnaire For Mental Component Summary (MCS) Score at Weeks 12 and 24 Change at Week 24	0.4 units on a scale Standard Deviation 10.45	1.7 units on a scale Standard Deviation 10.81

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full analysis set included all randomized participants who took at least 1 dose of study drug and had the baseline SLEDAI-2K total score, BILAG 2004 body system scores, and the PhGA score. Number analyzed = participants evaluable at specified timepoint.

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 defined as ≥1. The total maximum score is 47, and increasing score indicates increasing disease damage severity.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=90 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Baseline	0.7 units on a scale Standard Deviation 1.30	0.6 units on a scale Standard Deviation 1.08
Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Change at Week 24	-0.1 units on a scale Standard Deviation 0.47	-0.1 units on a scale Standard Deviation 0.37

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety analysis set included all randomized participants who took at least 1 dose of study drug.

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 in Reported AE section.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=91 Participants Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Number of Participants With Adverse Events (AEs)	81 Participants	77 Participants

Adverse Events

Placebo

Serious events: 13 serious events

Other events: 58 other events

Deaths: 0 deaths

CEP-33457

Serious events: 9 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=92 participants at risk Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=91 participants at risk Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Blood and lymphatic system disorders Anaemia	0.00% 0/92 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Blood and lymphatic system disorders Haemolytic anaemia	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Endocrine disorders Goitre	0.00% 0/92 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Gastrointestinal disorders Nausea	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
General disorders Medical device complication	0.00% 0/92 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 2 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Immune system disorders Drug hypersensitivity	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Infections and infestations Bronchitis	0.00% 0/92 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Infections and infestations Cellulitis	0.00% 0/92 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Infections and infestations Gastroenteritis viral	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Infections and infestations Staphylococcal sepsis	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Injury, poisoning and procedural complications Lower limb fracture	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myositis	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Cognitive disorder	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Convulsion	2.2% 2/92 • Number of events 2 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Encephalopathy	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Ischaemic stroke	0.00% 0/92 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Paraesthesia	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Polyneuropathy	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Syncope	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Renal and urinary disorders Lupus nephritis	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Systemic lupus erythematosus rash	0.00% 0/92 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	1.1% 1/91 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Vascular disorders Thrombophlebitis superficial	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Vascular disorders Venous insufficiency	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	0.00% 0/91 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.

Measure	Placebo n=92 participants at risk Participants received placebo matched to CEP-33457 SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).	CEP-33457 n=91 participants at risk Participants received CEP-33457 200 mcg SC every 4 weeks for 20 weeks (Day 1, Weeks 4, 8, 12, 16, and 20).
Gastrointestinal disorders Diarrhoea	8.7% 8/92 • Number of events 10 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	6.6% 6/91 • Number of events 10 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Gastrointestinal disorders Nausea	7.6% 7/92 • Number of events 11 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	5.5% 5/91 • Number of events 7 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	3.3% 3/92 • Number of events 3 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	6.6% 6/91 • Number of events 7 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
General disorders Fatigue	4.3% 4/92 • Number of events 5 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	6.6% 6/91 • Number of events 7 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
General disorders Injection site erythema	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	7.7% 7/91 • Number of events 23 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
General disorders Pyrexia	7.6% 7/92 • Number of events 10 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	4.4% 4/91 • Number of events 5 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	7.6% 7/92 • Number of events 7 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	7.7% 7/91 • Number of events 7 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	9.8% 9/92 • Number of events 11 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	7.7% 7/91 • Number of events 9 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Infections and infestations Urinary tract infection	9.8% 9/92 • Number of events 10 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	3.3% 3/91 • Number of events 6 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Injury, poisoning and procedural complications Contusion	5.4% 5/92 • Number of events 6 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	3.3% 3/91 • Number of events 3 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Investigations Weight decreased	5.4% 5/92 • Number of events 5 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	3.3% 3/91 • Number of events 3 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	7.6% 7/92 • Number of events 10 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	13.2% 12/91 • Number of events 15 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthritis	5.4% 5/92 • Number of events 9 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	17.6% 16/91 • Number of events 22 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	5.4% 5/92 • Number of events 5 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	3.3% 3/91 • Number of events 3 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.1% 1/92 • Number of events 1 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	5.5% 5/91 • Number of events 5 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	3.3% 3/92 • Number of events 3 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	7.7% 7/91 • Number of events 7 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	9.8% 9/92 • Number of events 16 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	12.1% 11/91 • Number of events 14 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Nervous system disorders Headache	9.8% 9/92 • Number of events 9 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	8.8% 8/91 • Number of events 11 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	6.5% 6/92 • Number of events 6 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	4.4% 4/91 • Number of events 4 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Systemic lupus erythematosus rash	13.0% 12/92 • Number of events 22 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.	12.1% 11/91 • Number of events 15 • Baseline up to Week 24 Safety analysis set included all randomized participants who took at least 1 dose of study drug.