A Long-Term Study of the Safety and Tolerability of Repea... | NCT01240694

Status Module

Label	Type	Description	Intervention Names
CEP-33457	Experimental	Participants will receive 200 micrograms (mcg) of CEP-33457	Drug: CEP-33457

Name	Type	Description	Arm Group Labels	Other Names
CEP-33457	Drug	CEP-33457 will be administered subcutaneously per dose specified in the arm description.	CEP-33457

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included clinically significant vitals, labs, and physical examination findings. Serious adverse events (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.	Baseline up to Week 72
Number of Participants Who Received Concomitant Medications	Any concomitant therapy or medication taken while the participant received study drug.	Baseline up to Week 72

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Achieving a Clinical Response Using the Systemic Lupus Erythematosus (SLE) Responder Index (SRI)	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=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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The participant has an established diagnosis of SLE as defined by ACR Classification Revised Criteria. The diagnosis is fulfilled provided that at least 4 criteria are met.
The participant previously participated in and completed at least Visit 8 (Week 24) the Cephalon sponsored clinical study with CEP-33457 (study C33457/2047) and, in the investigator's opinion, would benefit from continued participation in a clinical study.
Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing potential, using a medically accepted method of contraception, and must agree to continued use of this method for the duration of the study and for 30 days after discontinuation of study drug treatment.

Exclusion Criteria:

The participant has New York Heart Association (NYHA) Class III or IV congestive heart failure.
The participant has an estimated glomerular filtration rate (eGFR) of less than 30 milliliters (mL)/minute (min)/1.73 square meter (m^2) (via Modification of Diet in Renal Disease [MDRD] equation).
The participant has an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value greater than 2 times the upper limit of normal (ULN) or a total bilirubin level greater than 1.5 times ULN.
The participant has a planned immunization with a live or live attenuated vaccine within 3 months prior to administration of the first dose of study drug and for 3 months after administration of the last dose of study drug.
The participant has any clinically significant abnormalities on electrocardiogram (ECG) that are not related to SLE, as determined by the investigator. Participants with stable ECG changes without evidence of active cardiovascular disease may participate at the discretion of the investigator and medical monitor.
The participant has an ongoing active systemic infection requiring treatment or a history of severe infection, such as hepatitis or pneumonia, in the 3 months prior to administration of the first dose of study drug. Less severe infections in the 3 months prior to administration of the first dose of study drug are permitted at the discretion of the investigator and medical monitor.
The participant has any concomitant medical condition unrelated to SLE that may interfere with his or her safety or with evaluation of the study drug, as determined by the investigator.
The participant has a history of a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab).
The participant has a known positive history of antibodies to human immunodeficiency virus (HIV) or HIV disease.
The participant has a history of alcohol or substance dependence or abuse (with the exception of nicotine), according to the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, Fourth Edition, Text Revision (DSM-IV-TR), within 3 months of the screening visit for study C33457/2047, or has current substance abuse.
The participant has a history of severe allergic reactions to or hypersensitivity to any component of the study drug.
The participant is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
The participant has undergone or is undergoing treatment with another investigational drug for the treatment of lupus within 6 months prior to the 1st dose of study drug or has received any other investigational drug for any other condition within 30 days prior to the 1st dose of study drug, except for treatment with CEP-33457 or placebo in study C33457/2047.
The participant has a known history of antibodies to CEP-33457.
The participant is unlikely to comply with the study protocol or is unsuitable for any other reason, as judged by the investigator or medical monitor.

Name	Affiliation	Role
Teva Medical Expert	Teva Branded Pharmaceutical Products R&D, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Teva Investigational Site 27		Birmingham	Alabama	35233	United States
Teva Investigational Site 20

ID	Title	Description
FG000	CEP-33457	Participants received 200 micrograms (mcg) of CEP-33457 subcutaneously (SC) every 4 weeks for a maximum of 17 doses (64 weeks).

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Adverse Events (AEs)

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included clinically significant vitals, labs, and physical examination findings. Serious adverse events (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.

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

Posted

Count of Participants

Participants

Baseline up to Week 72

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000136

Title

Denominators

Categories

Title	Measurements
	OG000117

Secondary

Number of Participants Achieving a Clinical Response Using the Systemic Lupus Erythematosus (SLE) Responder Index (SRI)

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=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.

Intent-to-treat (ITT) analysis set included all enrolled participants who took at least 1 dose of study drug.

Posted

Count of Participants

Participants

Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Secondary

Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Total Score

The SLEDAI-2K is a validated objective measure that assesses disease activity within the last 28 days before completion of the index. It 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, with higher scores representing increased disease activity.

ITT analysis set included all enrolled participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable at specified timepoint.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and Final Assessment (or Early Termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Number of Participants With British Isles Lupus Assessment Group 2004 (BILAG-2004) Response

The BILAG-2004 is a validated objective and subjective global measure of the SLE disease activity, based on the physician's intention to treat, and refers to disease activity within the last 4 weeks before completion of the index. It includes 97 clinical and laboratory components to evaluate SLE disease activity in 9 different body systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological). Each body 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=stab1e or mild disease; D=previous system involvement but no current disease activity; and E=no current disease activity and the body system has never been involved. BILAG 2004 response was defined as no new BILAG A body system score and no more than 1 new BILAG B body system score from baseline.

ITT analysis set included all enrolled participants who took at least 1 dose of study drug.

Posted

Count of Participants

Participants

Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts

Secondary

Number of Participants Showing No Worsening on Physician's Global Assessment (PhGA) Scale

The PhGA was completed by the physician using a 3-inch visual analog scale (VAS) labeled from 0=none to 3=severe. A change of greater than 0.3 point on the VAS indicates worsening. The number of participants showing no worsening are presented.

ITT analysis set included all enrolled participants who took at least 1 dose of study drug.

Posted

Count of Participants

Participants

Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Number of Participants Showing No Worsening on Patient's Global Assessment (PtGA) Scale

The PtGA was completed by the participant, using a 3-inch VAS labeled from 0=none to 3=severe. A change of greater than 0.3 point on the VAS indicated worsening. The number of participants showing no worsening are presented.

ITT analysis set included all enrolled participants who took at least 1 dose of study drug.

Posted

Count of Participants

Participants

Week 12, 24, 36, 48, 60, and 72

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Short-Form 36 (SF-36) Domain Scores

The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, 2) physical role functioning, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) emotional role functioning, and 8) mental health. All domains are scored on a scale from 0 (worst) to 100 (best), with higher scores representing the best possible health state. Change from baseline scores in the following individual standardized domains: Bodily pain, physical functioning, social functioning and vitality were presented.

ITT analysis set included all enrolled participants who took at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure and 'number analyzed' signifies participants evaluable for specified category.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 12, 24, 36, 48, 60 and final assessment (or early termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants

Secondary

Change From Baseline in the Biomarker: Anti-U1 Ribonucleoprotein Antibody (Anti-UI RNP Ab)

Anti-UI RNP Ab was measured from blood serum collected at specified time points.

Posted

Mean

Standard Deviation

units (U)/milliliter (mL)

Baseline, Week 12, 24, 36, 48, 60 and final assessment (or early termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Change From Baseline in the Biomarker: C-Reactive Protein (CRP)

CRP was measured from blood serum samples at specified time points.

Posted

Mean

Standard Deviation

milligrams (mg)/deciliter (dL)

Baseline, Week 12, 24, 36, 48, 60, and Final Assessment (or Early Termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Number of Participants With Anti-nuclear Antibodies (ANA)

Anti-nuclear antibodies (ANA) were measured from blood serum samples at specified time points.

Posted

Count of Participants

Participants

Week 12, 24, 36, 48, 60, and Final Assessment (or Early Termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Number of Participants With Mild to Moderate Flare, Severe Flare, and No Flare, Based on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) Flare Index

The SELENA Flare Index divides flares into 2 categories: mild/moderate and severe. A severe flare would lead to early withdrawal. The number of participants with mild to moderate flare, severe flare, and no flare at each visit during the treatment period were reported.

Posted

Count of Participants

Participants

Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and Final Assessment (or Early Termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Total Damage Score as Assessed by the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index

The SLICC/ACR damage index assesses specific comorbidities associated with SLE. It consists of 41 items and covers 12 body systems. Total damage scores were calculated using the 41 items. The total damage score ranges from 0 (no damage) to 47 (maximum disease damage severity) with higher scores indicating increasing disease damage severity.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 24, 48 and Final Assessment (or Early Termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Number of Participants Achieving Remission of Disease

Remission of disease was defined as a reduction of SLEDAI-2K score to 0. The SLEDAI-2K is a validated objective measure that assesses disease activity within the last 28 days before completion of the index. It 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, with higher scores representing increased disease activity.

ITT analysis set included all enrolled participants who took at least 1 dose of study drug. Here 'number analyzed' signifies participants evaluable at specified timepoint.

Posted

Count of Participants

Participants

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and Final Assessment (or Early Termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Number of Participants With Change in Steroid Dose

Number of participants with change in steroid dose (prednisone equivalent/day) were reported. The change in steroid dose was evaluated to determine the number of participants taking a dose less than 7.5 mg of prednisone equivalent/day, a dose of 7.5 mg prednisone equivalent/day or more, and none per day.

ITT analysis set included all enrolled participants who took at least 1 dose of study drug.

Posted

Count of Participants

Participants

From Baseline up to Final Assessment (or Early Termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Secondary

Number of Participants With Reactive and Non-Reactive Anti-CEP-33457 Antibodies

Immunogenicity was assessed by detection of the presence of specific anti-CEP-33457 antibodies in blood serum samples collected at the specified time points.

Posted

Count of Participants

Participants

Week 24, 48 and Final Assessment (or Early Termination [up to Week 72])

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000

Primary

Number of Participants Who Received Concomitant Medications

Any concomitant therapy or medication taken while the participant received study drug.

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

Posted

Count of Participants

Participants

Baseline up to Week 72

ID	Title	Description
OG000	CEP-33457	Participants received 200 mcg of CEP-33457 SC every 4 weeks for a maximum of 17 doses (64 weeks).

Units	Counts
Participants	OG000136

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cholecystitis	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Appendicitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Pneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected136 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Injury	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected136 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Convulsion	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Myelitis transverse	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Syncope	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected136 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00017 events10 affected136 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00012 events10 affected136 at risk
Bronchitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0009 events8 affected136 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00013 events11 affected136 at risk
Sinusitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00010 events10 affected136 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00025 events20 affected136 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00011 events10 affected136 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00015 events12 affected136 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00018 events15 affected136 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00010 events7 affected136 at risk
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00026 events18 affected136 at risk
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG00016 events10 affected136 at risk
Anxiety	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0007 events7 affected136 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0007 events7 affected136 at risk
Systemic lupus erythematosus rash	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG00017 events16 affected136 at risk

ID	Term
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases