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

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ClinicalTrials.gov Identifier: NCT01584388
Recruitment Status : Completed
First Posted : April 25, 2012
Results First Posted : July 2, 2017
Last Update Posted : July 2, 2017
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
John H. Stone, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Retroperitoneal Fibrosis
Autoimmune Pancreatitis
Sialadenitis
Pseudotumor
Intervention Drug: Rituximab
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rituximab
Hide Arm/Group Description Rituximab: Rituximab 1000 mg IV times two doses, separated by approximately 15 days.
Period Title: Overall Study
Started 30
Completed 30
Not Completed 0
Arm/Group Title Rituximab
Hide Arm/Group Description Rituximab: Rituximab 1000 mg IV times two doses, separated by approximately 15 days.
Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
Covient sample
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
<=18 years
0
   0.0%
Between 18 and 65 years
15
  50.0%
>=65 years
15
  50.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
48  (17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
4
  13.3%
Male
26
  86.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
1.Primary Outcome
Title IgG4-RD RI Score at Baseline and Six Months After Rituxan Treatment
Hide Description

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.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title IgG4-RD Responder Index 6 Months
Hide Arm/Group Description:
Scoring at baseline
IgG4-RD Responder Index 6 months after treatment
Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
11  (7) 1  (2)
2.Primary Outcome
Title Cumulative Glucocorticoid Use at Baseline and 6 Months
Hide Description Cumulative glucocorticoid therapy between baseline and 6 months.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
cumulative glucocorticoid use at 6 and compare them to baseline using paired T tests.
Arm/Group Title Glucocorticoid Treatment (Baseline) Glucocorticoid Use (6 Months)
Hide Arm/Group Description:
total prednisone dose equivalent (mg) admin in the 28 preceding enrollment)
total prednisone dose equivalent admin over 28 days prior to the 6 month study visit
Overall Number of Participants Analyzed 30 30
Mean (Full Range)
Unit of Measure: mg
42
(0 to 850)
15
(0 to 280)
3.Primary Outcome
Title No Disease Flares During Rituximab Treatment Phase
Hide Description

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)
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
number of subjects without disease flares during baseline to 6 month of treatment
Arm/Group Title Disease Flare
Hide Arm/Group Description:
no disease flare before month 6
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
23
  76.7%
4.Secondary Outcome
Title Retreatment With Rituximab for Disease Relapse
Hide Description Number of subjects that relapsed during the course of the trial
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Relapse Treatment
Hide Arm/Group Description:
Rituximab treatment for relapse
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
4
  13.3%
5.Secondary Outcome
Title Disease Response at 6 Months
Hide Description Decline of IgG4-RD Responder Index by at least two points for at least 6 months
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Disease Response at 6 Months
Hide Arm/Group Description:
Decline of IgG4-RD RI by at least 2 points and maintained at 6 months.
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
29
  96.7%
6.Secondary Outcome
Title Sustained Disease Response
Hide Description Decline of the IgG4-RD RI by at least two points and maintained for 12 months.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Disease Response at 12 Months
Hide Arm/Group Description:
Decline of IgG4-RD RI by at least 2 points and maintained at 12 months.
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
22
  73.3%
7.Secondary Outcome
Title Complete Remission
Hide Description IgG4-RD RI (including serum IgG4) of 0 at six months
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Complete Remission at 6 Months
Hide Arm/Group Description:
IgG-RD RI (exclusive of serum IgG4) of 0 at 6 months.
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
14
  46.7%
8.Secondary Outcome
Title Complete Remission IgG-RD RI (Exclusive of Serum IgG4) of 0 at 6 Months.
Hide Description IgG-RD RI (exclusive of serum IgG4) of 0 at 6 months.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Complete Remission at 6 Months, Exclusive of Serum IgG4
Hide Arm/Group Description:
IgG-RD RI (exclusive of serum IgG4) of 0 at 6 months.
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
18
  60.0%
9.Secondary Outcome
Title Complete Remission at Any Timepoint
Hide Description IgG4-RD RI = 0 at any point in the trial
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Complete Remission (Any Timepoint)
Hide Arm/Group Description:
IgG4-RD RI = 0 at any point in the trial
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
18
  60.0%
10.Secondary Outcome
Title Complete Remission (Any Timepoint), Exclusive of Serum IgG4
Hide Description IgG4-RD RI = 0 (exclusive of serum IgG4) at any point in the trial
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Complete Remission at Any Timepoint, Exclusive of Serum IgG4
Hide Arm/Group Description:
IgG4-RD RI = 0 (exclusive of serum IgG4) at any point in the trial
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
20
  66.7%
11.Secondary Outcome
Title Time to Disease Response
Hide Description Treatment phase up to 52 weeks (365 days)
Time Frame Mean days +/- standard deviation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Time to Disease Response
Hide Arm/Group Description:
Time to achievement of IgG4-RD RI improvement of > 2
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: Days
43  (37)
12.Secondary Outcome
Title Time to Relapse
Hide Description Treatment phase up to 52 weeks (365 days)
Time Frame Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Time to Relapse
Hide Arm/Group Description:
Time to increase in IgG4-RD RI and reinstitution of treatment
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: Days
210  (105)
13.Secondary Outcome
Title Time to Complete Remission
Hide Description Treatment phase up to 52 weeks (365 days)
Time Frame Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Time to Complete Remission
Hide Arm/Group Description:
Time to achievement of IgG4-RD RI of 0
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: Days
198  (87)
Time Frame 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.
Adverse Event Reporting Description 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;
 
Arm/Group Title Open Label Treatment With Rituximab
Hide Arm/Group Description Rituximab 1000 mg IV times two doses, separated by approximately 15 days
All-Cause Mortality
Open Label Treatment With Rituximab
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Open Label Treatment With Rituximab
Affected / at Risk (%) # Events
Total   5/30 (16.67%)    
Blood and lymphatic system disorders   
cold agglutininmediated   1/30 (3.33%)  1
Cardiac disorders   
unstable angina   1/30 (3.33%)  1
Eye disorders   
Surgery for pseudotumor   1/30 (3.33%)  1
Infections and infestations   
Legionella pneumophila pneumonia  [1]  1/30 (3.33%)  1
Klebsiella urinary tract infection  [2]  1/30 (3.33%)  1
Vascular disorders   
Amaurosis fugax  [3]  1/30 (3.33%)  1
Indicates events were collected by systematic assessment
[1]
The Legionella infection was present unrecognised at the time of the baseline infusion
[2]
Infection
[3]
amaurosis fugax leading to a carotid endarterectomy
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Open Label Treatment With Rituximab
Affected / at Risk (%) # Events
Total   0/30 (0.00%)    
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John H Stone
Organization: MGH Rheumatology
Phone: 617-726-7938
EMail: jhstone@partners.org
Layout table for additonal information
Responsible Party: John H. Stone, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01584388     History of Changes
Other Study ID Numbers: 2011p002414
First Submitted: April 22, 2012
First Posted: April 25, 2012
Results First Submitted: December 14, 2015
Results First Posted: July 2, 2017
Last Update Posted: July 2, 2017