Belimumab in Remission of VASculitis | NCT01663623

Status Module

Name	Class
GlaxoSmithKline	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo plus azathioprine	Placebo Comparator	Placebo IV plus oral azathioprine 2 mg/kg/day; placebo administered on Days 0, 14, 28, and then every 28 days until the end of the study. If the results in the double-blind period show that belimumab is safe and effective, then participants have the option to receive treatment with belimumab in a 6-month open-label extension phase. Placebo patients who opt to participate in the extension will receive belimumab 10 mg/kg IV every 28 days plus oral azathioprine 2 mg/kg/day for an additional 6 months.	Biological: Placebo Drug: Azathioprine
Belimumab 10 mg/kg plus azathioprine	Experimental	Belimumab 10 mg/kg IV plus oral azathioprine 2 mg/kg/day; belimumab administered on Days 0, 14, 28, and then every 28 days until the end of the study. If the results in the double-blind period show that belimumab is safe and effective, then participants have the option to continue treatment with belimumab in a 6-month open-label extension phase. Patients who opt to participate in the extension will continue to receive belimumab 10 mg/kg IV every 28 plus oral azathioprine 2 mg/kg/day days for an additional 6 months.	Biological: Belimumab 10 mg/kg Drug: Azathioprine

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Biological	Placebo	Placebo plus azathioprine
Belimumab 10 mg/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time to First Relapse	Time to relapse is defined as the number of days from Day 0 until the participant experienced a relapse (relapse date - treatment start date +1). Only post-baseline relapses were considered in these analyses. Only relapses occurring up to and including the last visit date in the double-blind treatment period were considered in these analyses. Intent-to-treat population comprised of all randomized participants who received at least one dose of study agent (belimumab or placebo). NA indicates that the data was not available as the Number of events is too low to estimate the value. Median and Inter-quartile range were presented and were based on Kaplan Meier estimates.	Approximately up to 4 years

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Major Relapse During the Double-blind Phase of the Study	Data for number of participants with major relapse [defined as experiencing at least 1 major Birmingham Vasculitis Activity Score (BVAS) item] during the double-bind phase of the study was reported. Analysis was performed using a Cox proportional hazard model.	Approximately up to 4 years

Eligibility Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Birmingham	Alabama	35294	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
30666823	Derived	Jayne D, Blockmans D, Luqmani R, Moiseev S, Ji B, Green Y, Hall L, Roth D, Henderson RB, Merkel PA; BREVAS Study Collaborators. Efficacy and Safety of Belimumab and Azathioprine for Maintenance of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Controlled Study. Arthritis Rheumatol. 2019 Jun;71(6):952-963. doi: 10.1002/art.40802. Epub 2019 Apr 16.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 26, 2015	Nov 27, 2017

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.
BG001	Belimumab 10 mg/kg	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.
BG002	Total	Total of all reporting groups

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

Time to First Relapse

Time to relapse is defined as the number of days from Day 0 until the participant experienced a relapse (relapse date - treatment start date +1). Only post-baseline relapses were considered in these analyses. Only relapses occurring up to and including the last visit date in the double-blind treatment period were considered in these analyses. Intent-to-treat population comprised of all randomized participants who received at least one dose of study agent (belimumab or placebo). NA indicates that the data was not available as the Number of events is too low to estimate the value. Median and Inter-quartile range were presented and were based on Kaplan Meier estimates.

Intent-to-treat population

Posted

Median

Inter-Quartile Range

Days

Approximately up to 4 years

ID	Title	Description
OG000	Placebo	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.
OG001	Belimumab 10 mg/kg	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.

Units	Counts
Participants	OG00052 OG00153

Title

Denominators

Categories

Title	Measurements
	OG000NA(789.0 to NA)Kaplan Meier statistics could not be estimated where the number of events is too low. Hence it is NA. OG001NA(NA to NA)Kaplan Meier statistics could not be estimated where the number of events is too low. Hence it is NA.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cox Proportional Hazards model	Analysis was adjusted for ANCA type, disease stage at induction and induction regimen	0.884	Cox proportional Hazards (Wald Chi Square)	Hazard Ratio (HR)	1.07			2-Sided	95	0.44	2.59			Analysis performed using a Cox Proportional Hazards model with covariates treatment group, Actual ANCA type, Actual disease stage at induction and Actual induction regimen.		Other

Secondary

Number of Participants With Major Relapse During the Double-blind Phase of the Study

Data for number of participants with major relapse [defined as experiencing at least 1 major Birmingham Vasculitis Activity Score (BVAS) item] during the double-bind phase of the study was reported. Analysis was performed using a Cox proportional hazard model.

Intent-to-treat population

Posted

Number

Participants

Approximately up to 4 years

ID	Title	Description
OG000	Placebo	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.
OG001	Belimumab 10 mg/kg	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.

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	Placebo	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered matching placebo intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 milligram per kilogram per day (mg/kg/day). In Belgium-only open-label extension, all participants received belimumab 10mg/day every 28 days until Week 24, with a final evaluation at Week 28.	0	52	16	52	33	52
EG001	Belimumab 10 mg/kg	Participants were administered induction therapy (corticosteroids and either cyclophosphamide or rituximab) in the 6 months leading up to randomization. After randomization, participants were administered belimumab 10 mg/kg intravenously over 1 hour, at Day 0, 14, 28 and every 28 days thereafter until 12 months after the last subject was randomized. All participants received oral azathioprine at a target dose of 2 mg/kg/day. In Belgium-only open-label extension, all participants received belimumab 10 mg/kg every 28 days until Week 24, with a final evaluation at Week 28.	1	53	18	53	32	53

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Cellulitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Influenza	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Neutropenic sepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Salmonellosis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Tuberculosis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Pneumothorax traumatic	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Post procedural discharge	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected52 at risk EG0010 affected53 at risk
General physical health deterioration	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Hypersensitivity	Immune system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0012 affected53 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Anal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Pneumomediastinum	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Chronic gastritis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Muscle contracture	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Idiopathic orbital inflammation	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Liver function test increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected52 at risk EG0011 affected53 at risk
Vasculitis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0010 affected53 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG00010 affected52 at risk EG0016 affected53 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0008 affected52 at risk EG0017 affected53 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0004 affected52 at risk EG0015 affected53 at risk
Bronchitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0006 affected52 at risk EG0011 affected53 at risk
Influenza	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0015 affected53 at risk
Gastroenteritis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0003 affected52 at risk EG0010 affected53 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected52 at risk EG0017 affected53 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected52 at risk EG0015 affected53 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected52 at risk EG0013 affected53 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected52 at risk EG0015 affected53 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected52 at risk EG0011 affected53 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0008 affected52 at risk EG00110 affected53 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected52 at risk EG0015 affected53 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected52 at risk EG0014 affected53 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0006 affected52 at risk EG0016 affected53 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected52 at risk EG0013 affected53 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected52 at risk EG0012 affected53 at risk
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0007 affected52 at risk EG0017 affected53 at risk
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected52 at risk EG0016 affected53 at risk
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0007 affected52 at risk EG0015 affected53 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected52 at risk EG0015 affected53 at risk
Hypertension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected52 at risk EG0013 affected53 at risk

ID	Term
D014657	Vasculitis
D014890	Granulomatosis with Polyangiitis
D001327	Autoimmune Diseases
D055953	Microscopic Polyangiitis
D056647	Systemic Vasculitis

ID	Term
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D017563	Lung Diseases, Interstitial
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D056648	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
D017445	Skin Diseases, Vascular
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D007154	Immune System Diseases
D059345	Cerebral Small Vessel Diseases
D002561	Cerebrovascular Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
D013872	Thionucleosides
D013457	Sulfur Compounds
D009930	Organic Chemicals
D015122	Mercaptopurine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides