NCT00094380

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Sep 2004

Geographic Reach
1 country

2 active sites

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

Study Start

First participant enrolled

September 1, 2004

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

October 16, 2004

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 18, 2004

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2006

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2006

Completed
Last Updated

January 11, 2017

Status Verified

January 1, 2017

Enrollment Period

1.3 years

First QC Date

October 16, 2004

Last Update Submit

January 10, 2017

Conditions

Lupus Erythematosus, SystemicLupus Nephritis

Keywords

SLELupusSystemic Lupus ErythematosusLupus Nephritis

Outcome Measures

Primary Outcomes (1)

  • Safety, as measured by the occurrence of adverse events

    Throughout study

Secondary Outcomes (3)

  • Renal function

    Throughout study

  • Lupus serology

    Throughout study

  • SLE disease activity

    Throughout study

Study Arms (3)

Dose-escalation portion: Low dose CTLA4-IgG4m (RG2077)

EXPERIMENTAL

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: CTLA4-IgG4m (RG2077)Drug: Cyclophosphamide

Part IIA: CTLA4-IgG4m

EXPERIMENTAL

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

Part IIA: Control Group

EXPERIMENTAL

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

Interventions

CTLA4-IgG4m (RG2077)DRUG
Dose-escalation portion: Low dose CTLA4-IgG4m (RG2077)Part IIA: CTLA4-IgG4m
CyclophosphamideDRUG
Dose-escalation portion: Low dose CTLA4-IgG4m (RG2077)Part IIA: CTLA4-IgG4mPart IIA: Control Group

Eligibility Criteria

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

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

  • Davidson A, Diamond B, Wofsy D, Daikh D. Block and tackle: CTLA4Ig takes on lupus. Lupus. 2005;14(3):197-203. doi: 10.1191/0961203305lu2136oa.

    PMID: 15807196RESULT

Related Links

MeSH Terms

Conditions

Lupus Erythematosus, SystemicLupus Nephritis

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Connective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System DiseasesGlomerulonephritisNephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • David Wofsy, MD

    University of California, San Francisco

    STUDY CHAIR

  • Betty Diamond, MD

    Columbia University

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 16, 2004

First Posted

October 18, 2004

Study Start

September 1, 2004

Primary Completion

January 1, 2006

Study Completion

January 1, 2006

Last Updated

January 11, 2017

Record last verified: 2017-01

Data Sharing

IPD Sharing
Will share

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.

Available IPD Datasets

Individual Participant Data Set (SDY798)Access
Study protocol synopsis; -Study summary; -design; -adverse event; -Assessment; -Medications, -demographics; -study files (SDY798)Access
Individual Participant Data Set (ITN002AI)Access
Informed Consent Form (ITN002AI)Access
Study synopsis, -schedule of events, -adverse events, et al. (ITN002AI)Access

Locations

US(2)