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

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00094380
First received: October 16, 2004
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Lupus Erythematosus, Systemic
Lupus Nephritis
Drug: CTLA4-IgG4m (RG2077)
Drug: Cyclophosphamide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Systemic Lupus Erythematosus With CTLA4-IgG4m Plus Cyclophosphamide: A Phase I/IIA Study

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Safety, as measured by the occurrence of adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Renal function [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Lupus serology [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • SLE disease activity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: September 2004
Study Completion Date: January 2006
Arms Assigned Interventions
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 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: CTLA4-IgG4m (RG2077) Drug: Cyclophosphamide
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: CTLA4-IgG4m (RG2077) Drug: Cyclophosphamide
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00094380

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Investigators
Study Chair: David Wofsy, MD University of California, San Francisco
Study Chair: Betty Diamond, MD Columbia University
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00094380     History of Changes
Other Study ID Numbers: DAIT ITN002AI
Study First Received: October 16, 2004
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
SLE
Lupus
Systemic Lupus Erythematosus
Lupus Nephritis

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Lupus Nephritis
Nephritis
Autoimmune Diseases
Connective Tissue Diseases
Glomerulonephritis
Immune System Diseases
Kidney Diseases
Urologic Diseases
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014