Trial Outcomes & Findings for Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis (NCT NCT02169219)

Results Overview

We examined whether an 8-week glucocorticoid course in combination with rituximab (RTX) would induce disease remission in patients with AAV. The primary outcome was disease remission off steroids at 6 months.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

6 months

Results posted on

2021-06-25

Participant Flow

* New diagnosis or flare of previously diagnosed disease in patients followed in the Massachusetts General Hospital (MGH) Rheumatology or Nephrology Units. * New diagnosis or flare of previously diagnosed disease in patients hospitalized at MGH.

Participant milestones

Participant milestones
Measure	Glucocorticoids and Rituximab All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit.
Overall Study STARTED	20
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Glucocorticoids and Rituximab All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit.
Overall Study Lack of Efficacy	6

Baseline Characteristics

Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glucocorticoids and Rituximab n=20 Participants This is a single-arm trial. All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit. Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab: Rituximab will be administered in four weekly doses at 375mg/m2
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Region of Enrollment United States	20 Participants n=5 Participants
Birmingham Vasculitis Activity Score for Wegener's Granulomatosis(BVAS/WG)	5 units on a scale n=5 Participants
Disease group Granulomatosis with polyangiitis (GPA)	14 Participants n=5 Participants
Disease group Microscopic polyangiitis (MPA)	6 Participants n=5 Participants
Disease group Indeterminate	0 Participants n=5 Participants
anti-neutrophil cytoplasmic antibody (ANCA) myeloperoxidase (MPO)	11 Participants n=5 Participants
anti-neutrophil cytoplasmic antibody (ANCA) proteinase (PR3)	7 Participants n=5 Participants
anti-neutrophil cytoplasmic antibody (ANCA) Negative	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

We examined whether an 8-week glucocorticoid course in combination with rituximab (RTX) would induce disease remission in patients with AAV. The primary outcome was disease remission off steroids at 6 months.

Outcome measures

Outcome measures
Measure	Glucocorticoids and Rituximab n=20 Participants Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab will be administered in four weekly doses at 375mg/m2
Complete Remission	14 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: Number of patients having a disease response

Number of patients achieving disease response defined as, no new disease manifestations; no worsening of existing disease; stable or improved BVAS/WG score at 4 weeks.

Outcome measures

Outcome measures
Measure	Glucocorticoids and Rituximab n=20 Participants Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab will be administered in four weekly doses at 375mg/m2
Disease Response	20 Participants

SECONDARY outcome

Timeframe: 8 weeks

Number of patients entering partial remission, defined as no new disease manifestations, no worsening of existing disease and BVAS/WG \< 3.

Outcome measures

Outcome measures
Measure	Glucocorticoids and Rituximab n=20 Participants Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab will be administered in four weekly doses at 375mg/m2
Partial Remission	20 Participants

SECONDARY outcome

Timeframe: 6 months

Number of patients entering sustained remission defined as BVAS/WG = 0, prednisone dose = 0 and no disease flares during the study period.

Outcome measures

Outcome measures
Measure	Glucocorticoids and Rituximab n=20 Participants Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab will be administered in four weekly doses at 375mg/m2
Sustained Complete Remission	14 Participants

SECONDARY outcome

Timeframe: 6 months

Number of limited flares defined as a new occurrence or worsening of one or more minor BVAS/WG items and a total BVAS/WG ≤ 3

Outcome measures

Outcome measures
Measure	Glucocorticoids and Rituximab n=20 Participants Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab will be administered in four weekly doses at 375mg/m2
Limited Flares	2 Participants

SECONDARY outcome

Timeframe: 6 months

Number of severe flares defined as flare with BVAS/WG \> 3 or experiencing one of the major BVAS/WG items

Outcome measures

Outcome measures
Measure	Glucocorticoids and Rituximab n=20 Participants Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab will be administered in four weekly doses at 375mg/m2
Severe Flares	5 Participants

SECONDARY outcome

Timeframe: 4 weeks

Number of early treatment failures defined as patients who have new or worsening disease manifestations assessed at 4 weeks after study entry

Outcome measures

Outcome measures
Measure	Glucocorticoids and Rituximab n=20 Participants Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab will be administered in four weekly doses at 375mg/m2
Early Treatment Failures	0 Participants

SECONDARY outcome

Timeframe: 24 months

The Vasculitis Damage Index (VDI) is a single-page catalog of damage items separated into 11 groupings of items by organ system. There are a total of 60 items. Each item is recorded if it occurred since the onset of vasculitis, has been present for at least 3 months, or occurred at least 3 months ago. Each item of damage is scored as present (1) or absent (0), yielding a maximum score of 60.

Outcome measures

Outcome measures
Measure	Glucocorticoids and Rituximab n=20 Participants Glucocorticoids: Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab will be administered in four weekly doses at 375mg/m2
Vasculitis Damage Index (VDI) Baseline VDI score	0 units on a scale Interval 0.0 to 1.0
Vasculitis Damage Index (VDI) 24 month VDI score	0.5 units on a scale Interval 0.0 to 2.0

Adverse Events

Glucocorticoids and Rituximab

Serious events: 11 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Glucocorticoids and Rituximab n=20 participants at risk Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: * 60mg for 2 weeks * 40mg for 2 weeks * 30mg for 1 week * 20mg for 1 week * 10mg for 1 week * 5mg for 1 week Rituximab: Rituximab will be administered in four weekly doses at 375mg/m2
Immune system disorders Severe flares	25.0% 5/20 • Number of events 5 • Reports of unanticipated problems involving risks to subjects or others are to be submitted to the IRB within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Adverse events were collected through the 6 month study duration. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria: 1\) hospitalization or prolonged hospitalization 2.)One severe flare - defined as BVAS/WG ≥ 3 or experiencing one of the major BVAS/WG items) 3.) unexpected and related to the investigation drug
Cardiac disorders myocardial infarction	5.0% 1/20 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are to be submitted to the IRB within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Adverse events were collected through the 6 month study duration. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria: 1\) hospitalization or prolonged hospitalization 2.)One severe flare - defined as BVAS/WG ≥ 3 or experiencing one of the major BVAS/WG items) 3.) unexpected and related to the investigation drug
Cardiac disorders atrial fibrillation,	5.0% 1/20 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are to be submitted to the IRB within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Adverse events were collected through the 6 month study duration. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria: 1\) hospitalization or prolonged hospitalization 2.)One severe flare - defined as BVAS/WG ≥ 3 or experiencing one of the major BVAS/WG items) 3.) unexpected and related to the investigation drug
Immune system disorders syncope	5.0% 1/20 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are to be submitted to the IRB within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Adverse events were collected through the 6 month study duration. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria: 1\) hospitalization or prolonged hospitalization 2.)One severe flare - defined as BVAS/WG ≥ 3 or experiencing one of the major BVAS/WG items) 3.) unexpected and related to the investigation drug
Endocrine disorders Thyroid maligancy	10.0% 2/20 • Number of events 2 • Reports of unanticipated problems involving risks to subjects or others are to be submitted to the IRB within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Adverse events were collected through the 6 month study duration. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria: 1\) hospitalization or prolonged hospitalization 2.)One severe flare - defined as BVAS/WG ≥ 3 or experiencing one of the major BVAS/WG items) 3.) unexpected and related to the investigation drug
Reproductive system and breast disorders Uterine malignancy	5.0% 1/20 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are to be submitted to the IRB within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Adverse events were collected through the 6 month study duration. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria: 1\) hospitalization or prolonged hospitalization 2.)One severe flare - defined as BVAS/WG ≥ 3 or experiencing one of the major BVAS/WG items) 3.) unexpected and related to the investigation drug

Other adverse events

Adverse event data not reported

Additional Information

Dr. John Stone

Massachusetts General Hospital, Division of Rheumatology

Phone: 617-643-2140

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place