NCT00595335

Brief Summary

This study is being done to investigate the effects (good and bad) of Rituximab for the treatment of an autoimmune eye disease called Graves' ophthalmopathy. This disease has proven to be difficult to treat. Rituximab is a monoclonal antibody that depletes a line of cells involved in the autoimmune response. The study hypotheses is that rituximab is effective in the treatment of patients with moderate to severe active Graves' ophthalmopathy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Apr 2008

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 1, 2008

Completed
15 days until next milestone

First Posted

Study publicly available on registry

January 16, 2008

Completed
3 months until next milestone

Study Start

First participant enrolled

April 1, 2008

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2013

Completed
9 months until next milestone

Results Posted

Study results publicly available

June 3, 2014

Completed
Last Updated

January 1, 2016

Status Verified

December 1, 2015

Enrollment Period

4.9 years

First QC Date

January 1, 2008

Results QC Date

March 26, 2014

Last Update Submit

December 30, 2015

Conditions

Keywords

Thyroid-associated ophthalmopathyRituximabProptosis

Outcome Measures

Primary Outcomes (1)

  • Change in Clinical Activity Score (CAS)

    The clinical activity score (CAS), for Grave's ophthalmopathy has become a widely accepted tool to assess disease activity and help decide the management of the condition. The CAS, which is based on classical signs of inflammation (pain, redness, and swelling), consists of 7 equally weighted items. The total CAS (as used in this study) may range from 0 to 7. The higher the CAS, the greater degree of inflammation is present. A drop in CAS of 2 or more points suggests an improvement in the inflammatory components of the disease. A CAS ≥3 implies active disease.

    baseline, 6 months after the first infusion

Secondary Outcomes (7)

  • Failure Rate

    6 months after first infusion, 12 months after first infusion

  • Change in Disease Severity

    baseline, 6 months after first infusion

  • Change in Proptosis

    baseline, 12 months after first infusion

  • Change in Lid Fissure

    baseline, 6 months after first infusion

  • Change in Extraocular Motility

    baseline, 6 months after first infusion, 12 months after first infusion

  • +2 more secondary outcomes

Study Arms (2)

Rituximab

EXPERIMENTAL

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Drug: RituximabDrug: Methylprednisolone

Placebo

PLACEBO COMPARATOR

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Drug: Saline

Interventions

Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Also known as: Rituxan, MabThera
Rituximab
SalineDRUG

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Placebo

Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Also known as: Medrol, Solu-Medrol
Rituximab

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with clinical activity score (CAS) of ≥4 and moderate to severe disease severity, as defined by thyroid eye disease severity scale based on the first letter of the defining characteristic of each class, the classification is known as: 'no signs or symptoms; only signs; soft tissue; proptosis; extraocular muscle; cornea; sight loss' (NOSPECS) score
  • Euthyroid for at least 6-8 weeks
  • No immediate need for decompression surgery
  • With disease progression over the previous 1-2 months or without evident improvement in the prior 6 months.

You may not qualify if:

  • Corticosteroid use in the preceding 4 weeks
  • HIV, hepatitis C or hepatitis B infections
  • Denied consent for HIV or hepatitis testing
  • Mild or inactive Graves' ophthalmopathy
  • Orbital radiotherapy within 18 months or orbital surgery within the past year
  • Absolute neutrophil count \< 1,500/mm\^3
  • Pregnant or nursing patients
  • Coronary artery disease, congestive heart failure, significant arrhythmias, significant infection or immunodeficiency, other serious illnesses

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

  • Stan MN, Garrity JA, Carranza Leon BG, Prabin T, Bradley EA, Bahn RS. Randomized controlled trial of rituximab in patients with Graves' orbitopathy. J Clin Endocrinol Metab. 2015 Feb;100(2):432-41. doi: 10.1210/jc.2014-2572. Epub 2014 Oct 24.

MeSH Terms

Conditions

Graves OphthalmopathyExophthalmos

Interventions

RituximabSodium ChlorideMethylprednisoloneMethylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Eye Diseases, HereditaryEye DiseasesGraves DiseaseOrbital DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGoiterThyroid DiseasesEndocrine System DiseasesHyperthyroidismAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium CompoundsPrednisolonePregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Results Point of Contact

Title
Dr. Rebecca S. Bahn
Organization
Mayo Clinic

Study Officials

  • Rebecca S Bahn, MD

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Medicine, Consultant in Endocrinology, Mayo Clinic

Study Record Dates

First Submitted

January 1, 2008

First Posted

January 16, 2008

Study Start

April 1, 2008

Primary Completion

March 1, 2013

Study Completion

September 1, 2013

Last Updated

January 1, 2016

Results First Posted

June 3, 2014

Record last verified: 2015-12

Locations