Treating Systemic Lupus Erythematosus (SLE) Patients With CTLA4-IgG4m (RG2077)

January 10, 2017 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Treatment of Systemic Lupus Erythematosus With CTLA4-IgG4m Plus Cyclophosphamide: A Phase I/IIA Study

The purpose of this study is to examine the safety of a single dose of RG2077 in patients with systemic lupus erythematosus (SLE) who are currently receiving cyclophosphamide. This study will also determine if RG2077 is effective in decreasing disease activity in these patients.

Study hypothesis: CTLA4-Ig mediates a T cell costimulatory blockade that effectively induces an antigen-specific nonresponsiveness in T cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

SLE is a chronic, inflammatory autoimmune disorder that may affect many organ systems, including the skin, joints, and internal organs. RG2077 has been studied for use in multiple sclerosis, another autoimmune disorder. This study will evaluate the safety and efficacy of RG2077 in SLE patients who are currently receiving cyclophosphamide.

This trial is composed of two parts. The first part is a dose-escalation study in which participants will receive one of two doses of RG2077 (0.2 mg/kg or 2 mg/kg); this part of the study will last 60 days. At screening, patients will have an IV catheter inserted into their arms for administration of cyclophosphamide and RG2077. Patients will also have medical and medication history assessments, a comprehensive physical exam, and blood and urine tests. There are 5 study visits for the first part of the trial; these will occur at screening, at study entry, and Days 1, 14, and 28. Selected visits will include physical exam, vital signs measurement, blood and urine tests, and disease activity assessment. At Days 7 and 60, patients will be contacted by phone to report their medication history and any adverse effects they have experienced.

The second part of the study will evaluate a single 10 mg/kg dose of RG2077; this part of the study will last 90 days. In the study, participants will be randomly assigned to one of two groups. At the start of the study, Group 1 participants will receive RG2077 and cyclophosphamide and Group 2 participants will receive cyclophosphamide only. There will be 9 study visits; these will occur at study screening, study entry, and Days 1, 4, 7, 14, 28, and 60. At selected visits, patients will undergo physical exam, vital signs measurement, blood tests and urine tests, and disease activity assessment.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of SLE by American College of Rheumatology (ACR) criteria
  • Concurrent treatment with intravenous cyclophosphamide (500 to 1000 mg/m2) for at least one of the following manifestations of lupus: World Health Organization (WHO) class III, IV, or V lupus nephritis; British Isles Lupus Assessment Group (BILAG) score of A for vasculitis; BILAG score of A for cytopenia; BILAG score of A for nervous system
  • Stable medication regimen for at least 4 weeks prior to study entry
  • Weight between 40 kg (88.2 lbs) and 125 kg (275.6 lb)
  • Willing to use acceptable forms of contraception

Exclusion Criteria:

  • Moderately severe anemia (hemoglobin less than 8 mg/dL)
  • Neutropenia (absolute neutrophil count less than 1,500/mm3)
  • Thrombocytopenia (platelets less than 50,000/mm3)
  • Positive tuberculin (PPD) test without evidence of prior treatment or administration of bacille Calmette-Guérin (BCG) vaccine
  • Active infections, including HIV and hepatitis B or C
  • Receipt of a live vaccine within 3 months of study entry
  • End-stage renal disease with creatinine clearance less than 20 ml/min/1.73 m2
  • History of cancer. Patients with a history of carcinoma in situ and treated basal and squamous cell carcinomas are not excluded.
  • Pregnant or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Dose-escalation portion: Low dose CTLA4-IgG4m (RG2077)
Three patients will receive a single intravenous infusion of 0.2 mg/kg CTLA4-IgG4m following the scheduled cyclophosphamide infusion on the same day. If one or more dose-limiting toxicities (CTC grade 3 or higher adverse event in the first 28 days after CTLA4-IgG4m administration that is possibly, probably, or definitely related to CTLA4-IgG4m (RG2077)). are observed, enrollment in the trial will be suspended pending DSMB review. If no dose-limiting toxicity is observed in the 0.2mg/kg dose, three patients will receive a single intravenous infusion of 2 mg/kg of CTLA4-IgG4m following the scheduled cyclophosphamide infusion on the same day. If one or more dose-limiting toxicities are observed, enrollment will be suspended pending review by the Data Safety and Monitoring Board (DSMB).If no dose-limiting toxicity is observed in the 2 mg/kg dose, treatment of patients with 10 mg/kg of CTLA4-IgG4m in combination with cyclophosphamide will proceed.
Drug: Cyclophosphamide
Drug: CTLA4-IgG4m (RG2077)
EXPERIMENTAL: Part IIA: CTLA4-IgG4m
Participants randomized to the CTLA4-IgG4m Arm will receive a single intravenous infusion of 10 mg/kg CTLA4-IgG4m (RG2077) following the scheduled cyclophosphamide infusion on the same day
Drug: Cyclophosphamide
Drug: CTLA4-IgG4m (RG2077)
EXPERIMENTAL: Part IIA: Control Group
Participants randomized to the control group will not receive treatment with CTLA4-IgG4m (RG2077); these participants will undergo all study evaluations with the exception of the CTLA4-IgG4m (RG2077) pharmacokinetic evaluations and immunogenicity evaluations.
Drug: Cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety, as measured by the occurrence of adverse events
Time Frame: Throughout study
Throughout study

Secondary Outcome Measures

Outcome Measure
Time Frame
Renal function
Time Frame: Throughout study
Throughout study
Lupus serology
Time Frame: Throughout study
Throughout study
SLE disease activity
Time Frame: Throughout study
Throughout study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Immune Tolerance Network (ITN)

Investigators

  • Study Chair: Betty Diamond, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2004

Primary Completion (ACTUAL)

January 1, 2006

Study Completion (ACTUAL)

January 1, 2006

Study Registration Dates

First Submitted

October 16, 2004

First Submitted That Met QC Criteria

October 16, 2004

First Posted (ESTIMATE)

October 18, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

January 11, 2017

Last Update Submitted That Met QC Criteria

January 10, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT ITN002AI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Participant level data and additional relevant materials are available to the public in 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: SDY798
    Information comments: ImmPort study identifier is SDY798.
  2. Study protocol synopsis; -Study summary; -design; -adverse event; -Assessment; -Medications, -demographics; -study files
    Information identifier: SDY798
    Information comments: ImmPort study identifier is SDY798.
  3. Individual Participant Data Set
    Information identifier: ITN002AI
    Information comments: TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.
  4. Informed Consent Form
    Information identifier: ITN002AI
    Information comments: TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.
  5. Study synopsis, -schedule of events, -adverse events, et al.
    Information identifier: ITN002AI
    Information comments: TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lupus Erythematosus, Systemic

Clinical Trials on Cyclophosphamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cyprus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe