A Phase 2 Study of Atacicept in Subjects With Relapsing M... | NCT00642902

NCT00642902

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Atacicept 25 mg	Experimental	Drug: Atacicept
Atacicept 75 mg	Experimental	Drug: Atacicept
Atacicept 150 mg	Experimental	Drug: Atacicept
Placebo	Placebo Comparator	Drug: Placebo matched to atacicept

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Atacicept	Drug	Atacicept will be administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan	Analysis of T1 Gd-enhancing lesions was done using magnetic resonance imaging (MRI) scans. Only post-baseline scans were included in the calculation of this endpoint (excluding the Study Day 1 scan which had been conducted before first dosing).	Weeks 12 to 36

Secondary Outcomes

Measure	Description	Time Frame
Number of New T1 Gd-enhancing Lesions Per Participant	Analysis of new T1 Gd-enhancing lesions was done using MRI scans.	Weeks 12, 24, 36
Percentage of Participants Free From Relapses	A relapse was defined as the fulfillment of all the following criteria: a) neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours; b) absence of fever or known infection (fever with temperature [axillary, orally, or intrauriculary] greater than (>) 37.5 degrees Celsius or 99.5 degrees Fahrenheit); and c) objective neurological impairment, correlating with the participant's reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. Percentage of participants free from relapses during 36-week treatment period was reported.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Medical Responsible	EMD Serono, an affiliate of Merck KGaA Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Phoenix	Arizona		United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24613349	Derived	Kappos L, Hartung HP, Freedman MS, Boyko A, Radu EW, Mikol DD, Lamarine M, Hyvert Y, Freudensprung U, Plitz T, van Beek J; ATAMS Study Group. Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol. 2014 Apr;13(4):353-63. doi: 10.1016/S1474-4422(14)70028-6. Epub 2014 Mar 6.

Label	URL
Related Info	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
FG001	Atacicept 25 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.

Intent-to-treat (ITT) population included all randomized participants.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
BG001	Atacicept 25 mg	Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.
BG002	Atacicept 75 mg	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks.
BG003	Atacicept 150 mg	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0003.07(1.40 to 6.77) OG0012.26(0.97 to 5.27) OG0022.30(1.08 to 4.92) OG003

Secondary

Number of New T1 Gd-enhancing Lesions Per Participant

Analysis of new T1 Gd-enhancing lesions was done using MRI scans.

ITT population included all randomized participants. 'n' signifies participants who were evaluable for this measure at given time points for each group, respectively.

Posted

Mean

Standard Deviation

lesions/participant

Weeks 12, 24, 36

ID	Title	Description
OG000	Placebo	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
OG001	Atacicept 25 mg	Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.
OG002	Atacicept 75 mg	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks.
OG003	Atacicept 150 mg

Secondary

Percentage of Participants Free From Relapses

A relapse was defined as the fulfillment of all the following criteria: a) neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours; b) absence of fever or known infection (fever with temperature [axillary, orally, or intrauriculary] greater than (>) 37.5 degrees Celsius or 99.5 degrees Fahrenheit); and c) objective neurological impairment, correlating with the participant's reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. Percentage of participants free from relapses during 36-week treatment period was reported.

ITT population included all randomized participants.

Posted

Number

percentage of participants

Baseline up to Week 36

ID	Title	Description
OG000	Placebo	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
OG001	Atacicept 25 mg	Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug up to 12 weeks after the last dose of the study drug that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with TEAEs included subjects with both non serious and serious TEAEs.

Safety population included all participants who received at least 1 dose of treatment (either active or placebo).

Posted

Number

participants

From the first dose of study drug administration up to 12 weeks after the last dose of the study drug

ID	Title	Description
OG000	Placebo	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
OG001	Atacicept 25 mg	Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	1	63	33	63
EG001	Atacicept 25 mg	Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.	3	63	30	63
EG002	Atacicept 75 mg	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks.	3	63	34	63
EG003	Atacicept 150 mg	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.	1	65	44	65

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Myocardial infarction	Cardiac disorders	MedDRA (11.1)	Non-systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG0030 affected65 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Acute psychosis	Psychiatric disorders	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Bronchopleural fistula	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Lung abscess	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Pyothorax	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Pneumonia	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0022 affected63 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Asthenia	General disorders	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Parathyroid tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Body temperature decreased	Investigations	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Otitis media acute	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site reaction	General disorders	MedDRA (11.1)	Non-systematic Assessment	EG0008 affected63 at risk EG00119 affected63 at risk EG00224 affected63 at risk EG00332 affected65 at risk
Fatigue	General disorders	MedDRA (11.1)	Non-systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0023 affected63 at risk EG003
Injection site pain	General disorders	MedDRA (11.1)	Non-systematic Assessment	EG0002 affected63 at risk EG0012 affected63 at risk EG0020 affected63 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0006 affected63 at risk EG0014 affected63 at risk EG0027 affected63 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0003 affected63 at risk EG0014 affected63 at risk EG0027 affected63 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0003 affected63 at risk EG0011 affected63 at risk EG0024 affected63 at risk EG003
Bronchitis	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0001 affected63 at risk EG0012 affected63 at risk EG0021 affected63 at risk EG003
Influenza	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment	EG0005 affected63 at risk EG0011 affected63 at risk EG0021 affected63 at risk EG003
Headache	Nervous system disorders	MedDRA (11.1)	Non-systematic Assessment	EG00011 affected63 at risk EG0018 affected63 at risk EG0023 affected63 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (11.1)	Non-systematic Assessment	EG0004 affected63 at risk EG0010 affected63 at risk EG0023 affected63 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (11.1)	Non-systematic Assessment	EG0004 affected63 at risk EG0013 affected63 at risk EG0021 affected63 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (11.1)	Non-systematic Assessment	EG0001 affected63 at risk EG0011 affected63 at risk EG0023 affected63 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (11.1)	Non-systematic Assessment	EG0002 affected63 at risk EG0013 affected63 at risk EG0021 affected63 at risk EG003

Sponsor voluntarily decided to prematurely terminate this trial due to an increase in multiple sclerosis (MS) disease activity observed in atacicept arms as compared to placebo during a routine independent data monitoring committee (IDMC) review.

Certain Agreements

ID	Term
C524618	TACI receptor-IgG Fc fragment fusion protein

Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.