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

NCT01584388 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2011p002414
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to evaluate the safety and effectiveness of rituximab in IgG4-RD.

Conditions

Retroperitoneal Fibrosis; Autoimmune Pancreatitis; Sialadenitis; Pseudotumor

Keywords

Type 1 autoimmune pancreatitis; IgG4-related sclerosing cholangitis; Chronic sclerosing sialadenitis; Lacrimal glands; Orbital pseudotumor; IgG4-related tubulointerstitial nephritis; Lymphadenopathy; Pachymeningitis; Aorta; Peri-aortitis; Retroperitoneal fibrosis; Riedel's thyroiditis

Outcome Measures

Primary Outcomes (3)

• IgG4-RD RI Score at Baseline and Six Months After Rituxan Treatment

  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.

  6 months

• Cumulative Glucocorticoid Use at Baseline and 6 Months

  Cumulative glucocorticoid therapy between baseline and 6 months.

  6 months

• No Disease Flares During Rituximab Treatment Phase

  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)

  Month 6

Secondary Outcomes (10)

• Retreatment With Rituximab for Disease Relapse

  12 months

• Disease Response at 6 Months

  6 months

• Sustained Disease Response

  12 months

• Complete Remission

  6 months

• Complete Remission IgG-RD RI (Exclusive of Serum IgG4) of 0 at 6 Months.

  6 months

Study Arms (1)

Rituximab

EXPERIMENTAL

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab 1000 mg IV times two doses, separated by approximately 15 days.

Also known as: Rituxan

Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included in the trial based on the following disease-specific criteria:
• Age 18 or older
• Diagnosis of IgG4-RD, based upon either pathological criteria\* (for those who have undergone biopsies) or clinical criteria.\*\* The criteria for pathological and clinical diagnoses are specified below.
• The subject can be either steroid-naive, in relapse, steroid dependent, or refractory to steroids. Subjects who are steroid dependent or refractory are eligible for enrollment if steroid dose has not been increased in the past 2 weeks, and their treating physician plans to withdraw steroids completely (by dose taper) within 8 weeks of starting rituximab.
• Pathological diagnosis:
• Histopathologic features consisting of a lymphoplasmacytic infiltrate and storiform fibrosis within involved organs. Other histopathologic features consistent with IgG4-RD (e.g., obliterative phlebitis) may be present but are not required.
• Either an IgG4/IgG plasma cell ratio of \> 50% within the affected organs or more than 10 IgG4-bearing plasma cells per high-power field.
• All patients with pathologic diagnoses will have their specimens reviewed by pathology investigators.
• \*\*Clinical diagnosis:
• Organ involvement in a pattern consistent with IgG4-RD. This must include dysfunction of one of the following organs: pancreas (autoimmune pancreatitis); salivary glands (chronic sclerosing sialadenitis); lacrimal glands; orbital pseudotumor; kidneys; lungs; lymph nodes; meninges; aorta (including aortitis/periaortitis and/or retroperitoneal fibrosis); thyroid gland (Riedel's thyroiditis). If a patient is enrolled with a clinical diagnosis alone, the diagnosis must be accompanied by both an imaging finding compatible with IgG4-RD and a 1.5-fold elevation in the serum IgG4 concentration.

You may not qualify if:

• Patients will be excluded from the study based on the following criteria:
• Disease-Specific Concerns: Excessive fibrosis within organs, such that a disease response to rituximab would not be expected.
• General Medical Concerns:
• Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment), or lactating.
• Inability to comply with study and/or follow-up procedures.
• Rituximab-Specific Concerns:
• History of HIV.
• Presence of active infection.
• New York Heart Association Classification III or IV heart disease (See Appendix D).
• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to randomization.
• Allergies: History of severe allergic reactions to human or chimeric monoclonal antibodies or murine protein.
• Uncontrolled disease: They show evidence of other uncontrolled disease, including drug and alcohol abuse, which that could interfere with participation in the trial according to the protocol.
• History of anti-human anti-chimeric antibody formation.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Related Publications (1)

• Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, Deshpande V, Smyrk TC, Chari S, Stone JH. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis. 2015 Jun;74(6):1171-7. doi: 10.1136/annrheumdis-2014-206605. Epub 2015 Feb 9.

  PMID: 25667206 DERIVED

MeSH Terms

Conditions

Retroperitoneal Fibrosis; Autoimmune Pancreatitis; Sialadenitis; Orbital Pseudotumor; Lymphadenopathy; Meningitis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pancreatitis, Chronic; Pancreatitis; Pancreatic Diseases; Digestive System Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Orbital Diseases; Eye Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Neuroinflammatory Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: John H Stone
• Organization: MGH Rheumatology

jhstone@partners.org

617-726-7938

Study Officials

• John H Stone, MD, MPH

  Massachusetts General Hospital (Rheumatology Unit)

  STUDY CHAIR

• Arezou Khosroshahi, MD

  Massachusetts General Hospital (Rheumatology Unit)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Clinical Rheumatology

Study Record Dates

• First Submitted: April 22, 2012
• First Posted: April 25, 2012
• Study Start: April 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2015
• Last Updated: July 2, 2017
• Results First Posted: July 2, 2017

Record last verified: 2017-05