The Efficacy and Safety of Atacicept in Combination With... | NCT00573157

ID	Type	Description	Link
493G01

Status Module

Name	Class
ZymoGenetics	INDUSTRY

Label	Type	Description	Intervention Names
Atacicept Plus Mycophenolate mofetil Plus Corticosteroids	Experimental		Drug: Atacicept Drug: Mycophenolate mofetil Drug: Corticosteroids
Placebo Plus Mycophenolate mofetil Plus Corticosteroids	Placebo Comparator		Drug: Mycophenolate mofetil Drug: Placebo Drug: Corticosteroids

Name	Type	Description	Arm Group Labels	Other Names
Atacicept	Drug	Atacicept will be administered at a dose of 150 milligram (mg) subcutaneously (SC) twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Confirmed Complete Renal Response (CRR), Partial Response, and Non-response	Complete renal response (CRR): from baseline, a return to within 10% of normal for renal function (assessed by calculated glomerular filtration rate [GFR]), improvement in proteinuria (urine protein/creatinine ratio <0.5) & resolution of hematuria. Partial response (PR): from baseline, a <= 10% worsening in renal function ( by calculated GFR); 50% improvement in proteinuria (assessed by urine protein/creatinine ratio) & resolution of hematuria, Non-response (NR): Neither criteria for CR or PR was met. Subjects were also deemed NR if they had treatment failure, regardless of CR or PR status. Subjects cannot be treatment failures. A response of CRR was confirmed if the Week 52 value is CRRand if the Week 48 value is CRR and at least 4 weeks apart from Week 52 /if the Week 48 value was missing/ less than 4 weeks from Week 52, then the Week 56 response must be CRR - if the Week 52 value was missing, then Week 48 and Week 56 must be CRR.	At Week 52

Measure	Description	Time Frame
Percentage of Participants With Normalization of Renal Function		At Week 52
Number of Participants With New Lupus Flares		At Week 52

Eligibility Module

Name	Affiliation	Role
Medical Responsible	EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Tulane University Hospital and Clinic Department of Internal Medicine		New Orleans	Louisiana		United States

PubMed Identifier	Type	Citation	Retractions
22325903	Derived	Ginzler EM, Wax S, Rajeswaran A, Copt S, Hillson J, Ramos E, Singer NG. Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther. 2012 Feb 7;14(1):R33. doi: 10.1186/ar3738.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Atacicept Plus Mycophenolate Mofetil Plus Corticosteroids	Atacicept was administered subcutaneously (SC) at a loading dose of 150 milligram (mg) twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose corticosteroids (CS) of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Atacicept Plus Mycophenolate Mofetil Plus Corticosteroids	Atacicept was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.
BG001	Placebo Plus Mycophenolate Mofetil Plus Corticosteroids	Placebo was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0004 BG0012 BG0026

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

Percentage of Participants With Confirmed Complete Renal Response (CRR), Partial Response, and Non-response

Complete renal response (CRR): from baseline, a return to within 10% of normal for renal function (assessed by calculated glomerular filtration rate [GFR]), improvement in proteinuria (urine protein/creatinine ratio <0.5) & resolution of hematuria. Partial response (PR): from baseline, a <= 10% worsening in renal function ( by calculated GFR); 50% improvement in proteinuria (assessed by urine protein/creatinine ratio) & resolution of hematuria, Non-response (NR): Neither criteria for CR or PR was met. Subjects were also deemed NR if they had treatment failure, regardless of CR or PR status. Subjects cannot be treatment failures. A response of CRR was confirmed if the Week 52 value is CRRand if the Week 48 value is CRR and at least 4 weeks apart from Week 52 /if the Week 48 value was missing/ less than 4 weeks from Week 52, then the Week 56 response must be CRR - if the Week 52 value was missing, then Week 48 and Week 56 must be CRR.

Due to early termination of the study caused by unanticipated safety issues, the outcome measure was not assessed.

Posted

At Week 52

ID	Title	Description
OG000	Atacicept Plus Mycophenolate Mofetil Plus Corticosteroids	Atacicept was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.
OG001	Placebo Plus Mycophenolate Mofetil Plus Corticosteroids	Placebo was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.

Units	Counts
Participants	OG0000 OG0010

Secondary

Percentage of Participants With Normalization of Renal Function

Due to early termination of the study caused by unanticipated safety issues, the outcome measure was not assessed.

Posted

At Week 52

ID	Title	Description
OG000	Atacicept Plus Mycophenolate Mofetil Plus Corticosteroids	Atacicept was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.
OG001	Placebo Plus Mycophenolate Mofetil Plus Corticosteroids	Placebo was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.

Secondary

Number of Participants With New Lupus Flares

Due to early termination of the study caused by unanticipated safety issues, the outcome measure was not assessed.

Posted

At Week 52

ID	Title	Description
OG000	Atacicept Plus Mycophenolate Mofetil Plus Corticosteroids	Atacicept was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.
OG001	Placebo Plus Mycophenolate Mofetil Plus Corticosteroids	Placebo was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Atacicept Plus Mycophenolate Mofetil Plus Corticosteroids	Atacicept was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.			3	4	4	4
EG001	Placebo Plus Mycophenolate Mofetil Plus Corticosteroids	Placebo was administered SC at a loading dose of 150 mg twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks. MMF was administered orally with a starting dose of 500 mg twice daily for 1 week, increased to 1000 mg twice daily for 1 week, then adjusted to 1500 mg or lower twice daily as per investigator's discretion. High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever was less was administered for 4 Weeks and tapered to 7.5 to 10 mg/day up to Week 12.			0	2	1	2

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA Version 11.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Syncope	Nervous system disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Empyema	Infections and infestations	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Pneumonia	Infections and infestations	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Pneumonia legionella	Infections and infestations	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Sepsis	Infections and infestations	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Renal failure acute	Renal and urinary disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Hypertensive crisis	Vascular disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected2 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected2 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Injection site erythema	General disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Injection site haematoma	General disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected2 at risk
Injection site pain	General disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Oedema	General disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Oedema peripheral	General disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Pyrexia	General disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Renal haematoma	Injury, poisoning and procedural complications	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0002 affected4 at risk EG0010 affected2 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Tachycardia	Cardiac disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected2 at risk
Atrial fibrillation	Cardiac disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Palpitations	Cardiac disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected2 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0002 affected4 at risk EG0010 affected2 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected2 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Dysgeusia	Nervous system disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected2 at risk
Tremor	Nervous system disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Leukocytoclastic vasculitis	Skin and subcutaneous tissue disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected2 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected2 at risk
Dry eye	Eye disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Influenza	Infections and infestations	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Blood immunoglobulin G decreased	Investigations	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Insomnia	Psychiatric disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Mood altered	Psychiatric disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Dysuria	Renal and urinary disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Renal failure acute	Renal and urinary disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk
Hypertension	Vascular disorders	MedDRA Version 12.0	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected2 at risk

ID	Term
D008181	Lupus Nephritis
D009393	Nephritis

ID	Term
D005921	Glomerulonephritis
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D008180	Lupus Erythematosus, Systemic
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
C524618	TACI receptor-IgG Fc fragment fusion protein
D009173	Mycophenolic Acid
D000305	Adrenal Cortex Hormones

ID	Term
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D005227	Fatty Acids
D008055	Lipids
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists