Trial Outcomes & Findings for Rituximab in IgG4-RD: A Phase 1-2 Trial (NCT NCT01584388)

NCT ID: NCT01584388

Last Updated: 2017-07-02

Results Overview

The IgG4-RD RI is then calculated by adding the individual organ scores.At each assessment, the physician enters a 0-4 score after the organ/site listed with: 0 = Normal or resolved 1. = Improved but still present 2. = Persistent (still active; unchanged from previous visit) 3. = New or recurrent disease activity while patient is off treatment 4. = Worsened or new disease despite treatment Definitions Organ/Site score: The overall level of IgG4-RD activity within a specific organ system Symptomatic: Is the disease manifestation in a particular organ system symptomatic? (Y = yes; N = no) Urgent disease: Disease that requires treatment immediately to prevent serious organ dysfunction (Y = yes; N = no) (Presence of urgent disease within an organ leads to DOUBLING of that organ system score) Damage: Organ dysfunction that has occurred as a result of IgG4-RD and is considered permanent (Y = yes; N = no) The Responder Index ranges from 0-60.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2017-07-02

Participant Flow

Participant milestones

Measure	Rituximab Rituximab: Rituximab 1000 mg IV times two doses, separated by approximately 15 days.
Overall Study STARTED	30
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Rituximab in IgG4-RD: A Phase 1-2 Trial

Baseline characteristics by cohort

Measure	Rituximab n=30 Participants Rituximab: Rituximab 1000 mg IV times two doses, separated by approximately 15 days.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants
Age, Continuous	48 Years STANDARD_DEVIATION 17 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

The IgG4-RD RI is then calculated by adding the individual organ scores.At each assessment, the physician enters a 0-4 score after the organ/site listed with:

0 = Normal or resolved

1. = Improved but still present

2. = Persistent (still active; unchanged from previous visit)

3. = New or recurrent disease activity while patient is off treatment

4. = Worsened or new disease despite treatment Definitions Organ/Site score: The overall level of IgG4-RD activity within a specific organ system Symptomatic: Is the disease manifestation in a particular organ system symptomatic? (Y = yes; N = no) Urgent disease: Disease that requires treatment immediately to prevent serious organ dysfunction (Y = yes; N = no) (Presence of urgent disease within an organ leads to DOUBLING of that organ system score) Damage: Organ dysfunction that has occurred as a result of IgG4-RD and is considered permanent (Y = yes; N = no)

The Responder Index ranges from 0-60.

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months n=30 Participants IgG4-RD Responder Index 6 months after treatment
IgG4-RD RI Score at Baseline and Six Months After Rituxan Treatment	11 units on a scale Standard Deviation 7	1 units on a scale Standard Deviation 2

PRIMARY outcome

Timeframe: 6 months

Population: cumulative glucocorticoid use at 6 and compare them to baseline using paired T tests.

Cumulative glucocorticoid therapy between baseline and 6 months.

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months n=30 Participants IgG4-RD Responder Index 6 months after treatment
Cumulative Glucocorticoid Use at Baseline and 6 Months	42 mg Interval 0.0 to 850.0	15 mg Interval 0.0 to 280.0

PRIMARY outcome

Timeframe: Month 6

Population: number of subjects without disease flares during baseline to 6 month of treatment

Disease flare measured by responder Index score:

At each assessment, the physician enters a 0-4 score after the organ/site listed with:

0 = Normal or resolved

1. = Improved but still present

2. = Persistent (still active; unchanged from previous visit)

3. = New or recurrent disease activity while patient is off treatment

4. = Worsened or new disease despite treatment Definitions Organ/Site score: The overall level of IgG4-RD activity within a specific organ system Symptomatic: Is the disease manifestation in a particular organ system symptomatic? (Y = yes; N = no) Urgent disease: Disease that requires treatment immediately to prevent serious organ dysfunction (Y = yes; N = no) (Presence of urgent disease within an organ leads to DOUBLING of that organ system score) Damage: Organ dysfunction that has occurred as a result of IgG4-RD and is considered permanent (Y = yes; N = no)

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
No Disease Flares During Rituximab Treatment Phase	23 Participants	—

SECONDARY outcome

Timeframe: 12 months

Number of subjects that relapsed during the course of the trial

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Retreatment With Rituximab for Disease Relapse	4 Participants	—

SECONDARY outcome

Timeframe: 6 months

Decline of IgG4-RD Responder Index by at least two points for at least 6 months

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Disease Response at 6 Months	29 Participants	—

SECONDARY outcome

Timeframe: 12 months

Decline of the IgG4-RD RI by at least two points and maintained for 12 months.

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Sustained Disease Response	22 Participants	—

SECONDARY outcome

Timeframe: 6 months

IgG4-RD RI (including serum IgG4) of 0 at six months

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Complete Remission	14 Participants	—

SECONDARY outcome

Timeframe: 6 months

IgG-RD RI (exclusive of serum IgG4) of 0 at 6 months.

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Complete Remission IgG-RD RI (Exclusive of Serum IgG4) of 0 at 6 Months.	18 Participants	—

SECONDARY outcome

Timeframe: 12 months

IgG4-RD RI = 0 at any point in the trial

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Complete Remission at Any Timepoint	18 Participants	—

SECONDARY outcome

Timeframe: 12 months

IgG4-RD RI = 0 (exclusive of serum IgG4) at any point in the trial

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Complete Remission (Any Timepoint), Exclusive of Serum IgG4	20 Participants	—

SECONDARY outcome

Timeframe: Mean days +/- standard deviation

Treatment phase up to 52 weeks (365 days)

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Time to Disease Response	43 Days Standard Deviation 37	—

SECONDARY outcome

Timeframe: Days

Treatment phase up to 52 weeks (365 days)

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Time to Relapse	210 Days Standard Deviation 105	—

SECONDARY outcome

Timeframe: Days

Treatment phase up to 52 weeks (365 days)

Outcome measures

Measure	IgG4-RD Responder Index n=30 Participants Scoring at baseline	6 Months IgG4-RD Responder Index 6 months after treatment
Time to Complete Remission	198 Days Standard Deviation 87	—

Adverse Events

Open Label Treatment With Rituximab

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Open Label Treatment With Rituximab n=30 participants at risk Rituximab 1000 mg IV times two doses, separated by approximately 15 days
Infections and infestations Legionella pneumophila pneumonia	3.3% 1/30 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria:requires inpatient hospitalization or prolongation of existing hospitalization;
Infections and infestations Klebsiella urinary tract infection	3.3% 1/30 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria:requires inpatient hospitalization or prolongation of existing hospitalization;
Blood and lymphatic system disorders cold agglutininmediated	3.3% 1/30 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria:requires inpatient hospitalization or prolongation of existing hospitalization;
Vascular disorders Amaurosis fugax	3.3% 1/30 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria:requires inpatient hospitalization or prolongation of existing hospitalization;
Cardiac disorders unstable angina	3.3% 1/30 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria:requires inpatient hospitalization or prolongation of existing hospitalization;
Eye disorders Surgery for pseudotumor	3.3% 1/30 • Number of events 1 • Reports of unanticipated problems involving risks to subjects or others are within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria:requires inpatient hospitalization or prolongation of existing hospitalization;

Other adverse events

Adverse event data not reported

Additional Information

John H Stone

MGH Rheumatology

Phone: 617-726-7938

Email: jhstone@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place