Lupus Erythematosus, SystemicPhase 1/2NCT00094380
Treating Systemic Lupus Erythematosus (SLE) Patients With CTLA4-IgG4m (RG2077)
A Phase 1/2 study testing CTLA4-IgG4m (RG2077) and Cyclophosphamide in people with Lupus Erythematosus, Systemic and Lupus Nephritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lupus Erythematosus, Systemic, Lupus Nephritis
- What is being tested?
- CTLA4-IgG4m (RG2077) and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2004to Jan 2006
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Columbia University Medical Center
New York, New York, 10032
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: 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.
Read the 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.
- Conditions
- Lupus Erythematosus, Systemic, Lupus Nephritis
- Being tested
- CTLA4-IgG4m (RG2077), Cyclophosphamide
- Keywords
- SLE, Lupus, Systemic Lupus Erythematosus, Lupus Nephritis
- Medical subject headings
- Lupus Erythematosus, Systemic, Lupus Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTLA4-IgG4m (RG2077)Drug
CyclophosphamideDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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. Receives: Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, as measured by the occurrence of adverse events
Measured: Throughout study
Secondary outcomes (3)
Renal function
Measured: Throughout study
Lupus serology
Measured: Throughout study
SLE disease activity
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2004 (estimated)
- Study startSep 2004
- Primary completionJan 2006
- Study completionJan 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lupus Erythematosus, SystemicStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Responsible party
- Sponsor
- Investigators
- David Wofsy, MD, Study chair, University of California, San FranciscoBetty Diamond, MD, Study chair, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00094380
- Sponsor's protocol ID
- DAIT ITN002AI
- Status last verified
- Jan 2017
- First submitted
- 16 Oct 2004
- Last updated
- 11 Jan 2017
- Results posted
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 15807196
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Systemic Lupus Erythematosus With CTLA4-IgG4m Plus Cyclophosphamide: A Phase I/IIA Study
- ClinicalTrials.gov ID
- NCT00094380
- Acronym / sponsor ID
- DAIT ITN002AI
- Conditions
- Lupus Erythematosus, Systemic, Lupus Nephritis
- Keywords
- SLE, Lupus, Systemic Lupus Erythematosus, Lupus Nephritis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Study start
- Sep 2004
- Primary completion
- Jan 2006 (actual)
- Study completion
- Jan 2006 (actual)
- First posted
- 18 Oct 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation portion: Low dose CTLA4-IgG4m (RG2077) | Experimental | Drug: CTLA4-IgG4m (RG2077), Drug: CyclophosphamideThree 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. |
| Part IIA: CTLA4-IgG4m | Experimental | Drug: CTLA4-IgG4m (RG2077), Drug: CyclophosphamideParticipants 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 |
| Part IIA: Control Group | Experimental | Drug: CyclophosphamideParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CTLA4-IgG4m (RG2077) | Drug | Dose-escalation portion: Low dose CTLA4-IgG4m (RG2077), Part IIA: CTLA4-IgG4m |
| Cyclophosphamide | Drug | Dose-escalation portion: Low dose CTLA4-IgG4m (RG2077), Part IIA: CTLA4-IgG4m, Part IIA: Control Group |
Primary outcome
Safety, as measured by the occurrence of adverse events
Time frame: Throughout study
3 secondary outcomes
Renal function
Time frame: Throughout study
Lupus serology
Time frame: Throughout study
SLE disease activity
Time frame: Throughout study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2017.
- Results publication: PubMed 15807196Davidson A, Diamond B, Wofsy D, Daikh D. Block and tackle: CTLA4Ig takes on lupus. Lupus. 2005;14(3):197-203. doi: 10.1191/0961203305lu2136oa.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Immune Tolerance Network (ITN)Link provided by the sponsor.
- Immune Tolerance Network (ITN) TrialShare: open public access to participant-level data available for this trialLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Wofsy, MD study chair
University of California, San Francisco
Betty Diamond, MD study chair
Columbia University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CTLA4-IgG4m (RG2077) and Cyclophosphamide in people with Lupus Erythematosus, Systemic and Lupus Nephritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety, as measured by the occurrence of adverse events (time frame: Throughout study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00094380, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2017.