Lupus Erythematosus, CutaneousPhase 1NCT02428309
Autologous Polyclonal Tregs for Lupus
A Phase 1 study testing Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells in people with Lupus Erythematosus, Cutaneous and Lupus Erythematosus, Discoid, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The primary purpose of this Phase 1 study is to evaluate the safety, tolerability, and effect of 3 different doses of Treg therapy in adults with skin (cutaneous) involvement of their lupus. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic
- What is being tested?
- Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Aug 2015to 3 Oct 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Ability to provide informed consent.
- Diagnosis of SLE by American College of Rheumatology (ACR) criteria or biopsy proven primary cutaneous lupus.
- Presence of ≥ 2 active cutaneous lupus lesions based on (1) visual morphology and (2) at least a grade 2 erythema on CLASI activity score. Histopathologic confirmation is required unless the active lesions are of the same morphology to previously histologically proven cutaneous lupus lesions.
- The cutaneous lupus lesions must include any of the following subtypes:
- Acute cutaneous lupus including maculopapular lupus rash and photosensitive lupus rash,
- Subacute cutaneous lupus,
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- Chronic cutaneous lupus including discoid lupus and hypertrophic (verrucous) lupus,
- Lupus timidus
- Positive test for Epstein-Barr virus (EBV) antibody.
- Adequate venous access to support draw of 400 mL whole blood and infusion of investigational therapy.
Who cannot join
- New onset of cutaneous lupus which has not been treated with broad spectrum sunscreen (UVA and UVB) in combination with either antimalarials or another systemic medication for at least 3 months.
- Prednisone dose > 15mg/day within the 30 days prior to screening.
- Addition of a new medication, or change in the dose of any background medication, used to treat any aspect of SLE. Specifically:
- addition or change in systemic glucocorticoids, antimalarials, methotrexate, mycophenolate mofetil, mycophenolic acid, azathioprine, cyclosporine, tacrolimus, thalidomide, lenalidomide, dapsone, acitretin, or isotretinoin within 90 days prior to screening
- treatment with cyclophosphamide within 90 days prior to screening.
- Doses of background medications at Screening visit:
Show all 56Show fewer
- hydroxychloroquine > 400 mg/day,
- chloroquine > 250 mg/day,
- quinacrine >100 mg/day,
- methotrexate > 25 mg/week,
- mycophenolate mofetil (MMF)> 3000 mg/day,
- mycophenolic acid > 720 mg/day BID,
- azathioprine > 200 mg/day,
- cyclosporine > 5 mg/day divided BID,
- tacrolimus > 6 mg/day
- thalidomide > 300 mg/day,
- lenalidomide > 10 mg/day,
- dapsone > 250 mg/day,
- acitretin > 50 mg/d (or > 1 mg/kg/day),
- isotretinoin > 120 mg/d (or > 2 mg/kg/day).
- Intravenous immunoglobulin (IVIG), plasmapheresis, or leukopheresis within the 90 days prior to screening.
- Use of rituximab within the 12 months prior to screening.
- Change in dosing frequency, concentration, or applied surface area of topical steroids, tacrolimus, and/or pimecrolimus within 4 weeks prior to screening.
- Active severe central nervous system lupus.
- SELENA-SLEDAI's seizure, psychosis, organic brain syndrome, visual disturbance,cranial nerve disorder, lupus headache, cerebrovascular accident (CVA), vasculitis,arthritis, myositis, mucosal ulcers, pleurisy, pericarditis, and fever scores > 8 total.
- Active lupus nephritis (spot protein / creatinine ratio > 1.0 mg/mg).
- End stage renal disease (estimated glomerular filtration rate [eGFR] < 20 ml/min/1.73m^2 using the CKD-EPI equation [53]).
- Drug induced lupus.
- Hemoglobin < 10 g/dL.
- White blood cell (WBC) count < 2,500/ mm^3 (equivalent to < 2.5 x10^9/L).
- Lymphocyte count < 625/mm^3 (equivalent to < 0.625 x10^9/L).
- Absolute neutrophil count < 1,500/mm3 (equivalent to < 1.5 x10^9/L).
- Platelets < 75,000/mm^3 (equivalent to < 75 x 10^9/L).
- Liver function test (aspartate aminotransferase [AST], alanine aminotransferase [ALT], or alkaline phosphatase [ALK]) results that are ≥ 2 times the upper limit of normal (ULN).
- Direct bilirubin > ULN.
- Active bacterial, viral, fungal, or opportunistic infections requiring systemic antiinfective therapy.
- Presence of positive purified protein derivative tuberculin skin test (PPD, > 5mm induration [regardless of Bacille Calmette Guerin (BCG) vaccine administration]) or positive or indeterminate QuantiFERON(R)-TB Gold In-Tube Test (QFT-G_IT) at screening.
- Evidence of infection with human immunodeficiency virus (HIV), hepatitis B (as assessed by HBsAg and anti-HBc) or hepatitis C.
- Detectable circulating EBV or cytomegalovirus (CMV) genomes or active infection.
- Chronic infection that is currently being treated with suppressive anti-infective therapy, including but not limited to tuberculosis, pneumocystis, CMV, herpes zoster, and atypical mycobacteria.
- Herpes simplex virus infection requiring chronic, suppressive therapy with an anti-viral medication.
- Receipt of a live-attenuated vaccine within 12 months prior to screening.
- Concomitant malignancies or a history of malignancy, with the exception of adequately treated basal and squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
- Pregnancy.
- Breastfeeding.
- Unwilling or unable to use reliable method(s) of contraception from four weeks prior to Day 0 throughout three months after Treg dosing (males) or for two years after Treg dosing (females). Note: investigators of female participants of childbearing potential on concurrent MMF, and those participants themselves, whether or not they plan to become pregnant, are strongly encouraged to participate in Mycophenolate Risk Evaluation and Mitigation Strategy (REMS).
- Use of an experimental therapeutic agent within the calendar year prior to screening.
- Use of biologic medications other than rituximab within the 90 days or 5 half-lives,whichever is greater, prior to screening.
- Concomitant medical condition that places the subject at risk by participating in this study, including but not limited to:
- another severe, systemic autoimmune disease or condition (besides lupus) requiring systemic immunosuppressive therapy (e.g., rheumatoid arthritis, systemic sclerosis, primary Sjogren's syndrome, primary vasculitis, psoriasis, multiple sclerosis, ankylosing spondylitis, and inflammatory bowel disease), or
- severe, progressive, or poorly controlled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease, either related or unrelated to SLE, or
- history of significant infection or recurrent infection that, in the investigator's opinion, places the subject at risk by participating in this study
- any other concomitant medical condition that, in the investigator's opinion, places the subject at risk by participating in this study.
- Comorbidities requiring glucocorticoid therapy, including those which have required three or more courses of systemic glucocorticoids within the previous 12 months.
- Current or history within the past year of substance abuse.
- Inability to comply with study and follow-up procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase I, Open-Label, Dose Escalation Trial Exploring the Safety and Tolerability of Autologous Polyclonal Regulatory T Cell Therapy in Adults With Active Cutaneous Lupus (ALE08)
The primary purpose of this Phase 1 study is to evaluate the safety, tolerability, and effect of 3 different doses of Treg therapy in adults with skin (cutaneous) involvement of their lupus. Targeting cutaneous disease offers the ability to control background therapy, readily detect clinical effects, and perform research analyses not only in blood but also skin. Safety, disease activity, and mechanism of Tregs will be evaluated. The intent is to support dose selection for a future larger efficacy trial in lupus.
Read the detailed description
The investigational therapy in this trial, regulatory T cells (Tregs), is evaluating an alternative to traditional immunosuppressive therapies for the treatment of systemic lupus erythematosus (SLE, lupus). Too frequently, aggressive therapies are inadequate in the control of the disease and have potent side effects and complications. The collection and expansion of one's own T cells harnesses a naturally occurring regulatory mechanism to restore self-tolerance in people with lupus. Tregs are a specialized subset of T cells that function to control the immune response. Studies have shown that in active lupus, the numbers and function of Treg cells are significantly decreased, which contributes to an overactive immune system and an increase in disease activity. The hope is that these naturally occurring Treg cells can be used for the treatment of autoimmune diseases, including lupus.
- Conditions
- Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic
- Being tested
- Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells
- Keywords
- active cutaneous lupus, systemic lupus erythematosus (SLE), autologous polyclonal regulatory T cell Therapy, polyclonal Tregs for treatment of lupus
- Medical subject headings
- Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ex vivo Expanded Human Autologous Polyclonal Regulatory T CellsBiological
Also called Ex vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Treg Cohort | Experimental | 3-6 participants will receive a single infusion of 1 x 10^ 8 autologous polyclonal Tregs (ex vivo selected and expanded) Receives: Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells |
| Medium Dose Treg Cohort | Experimental | Sequential dose escalation, 3-6 subjects will receive a single infusion of 4 x 10^ 8 autologous polyclonal Tregs (ex vivo selected and expanded) Receives: Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells |
| High Dose Treg Cohort | Experimental | Sequential dose escalation, 3-6 participants will receive a single infusion of 16 x 10^ 8 autologous polyclonal Tregs (ex vivo selected and expanded) Receives: Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Significant Adverse Events (AEs) Through Week 48
A significant adverse event is any related National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0 Grade 3 or higher AE or any related serious adverse event. Related is defined as being possibly, probably, or definitely related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.
Measured: From time of signed informed consent to Week 48
Secondary outcomes (19)
Number of Significant Adverse Events (AEs) Through Week 152
A significant adverse event is any related National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0 Grade 3 or higher AE or any related serious adverse event. Related is defined as being possibly, probably, or definitely related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.
Measured: From time of signed informed consent to Week 152
Number of Grade 3 or Higher Adverse Events (AEs) Through Week 152
Adverse events (AEs) Grade 3 or higher were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0.
Measured: From time of signed informed consent to Week 152
Number of Infection-Related Adverse Events (AEs) Through Week 152
If the adverse event was believed to be caused by a viral, bacterial, or fungal organism, regardless of whether it was treated with antibiotics or not, then it was classified as infection-related.
Measured: From time of signed informed consent to Week 152
Number of Lupus Flares Through Week 152 by Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Criteria
An activity score increase of ≥4 CLASI points defines a flare. A mild/moderate flare includes at least one of the following SELENA-SLEDAI criteria: Increase in the SLEDAI Score of ≥3 points, new or worse discoid, photosensitive, profundus, cutaneous vasculitis, bullous lupus, nasopharyngeal ulcers, pleuritic, pericarditis, arthritis, fever attributable to SLE; increase in prednisone (<0.5 mg/kg/day); added NSAID or Plaquenil; increase in PhGA (<2.5 [on a 3.0 indexed VAS scale]). A severe flare includes at least one of the following SELENA-SLEDAI criteria: Increase of >12 in the SLEDAI Score; new or worse CNS-SLE, vasculitis, nephritis, myositis, platelet count <60,000/mm^3, hemolytic anemia with hemoglobin <7% or decrease in hemoglobin >3%; prednisone >0.5 mg/kg/day; new Cyclophosphamide, Azathioprine, Methotrexate, Mycophenolate Mofetil, or hospitalization attributable to SLE; increase in PhGA to >2.5.
Measured: From time of signed informed consent to Week 152
Number Infusion-Related Adverse Events (AEs) Within 24 Hours of Infusion
Any infusion-related adverse events Grade 1 or higher within 24 hours of polyclonal Treg infusion. This study graded the severity of adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0.
Measured: From time of infusion to 24 hours post infusion
Change From Baseline: Alkaline Phosphatase (ALK), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)
Change=Post Baseline value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values are based on subject age, gender, and the specific laboratory methods that were used to determine the lab values.
Measured: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in g/dL: Albumin, Hemoglobin
Change=Post Baseline value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values.
Measured: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in mg/dL: Total Bilirubin, Creatinine
Change=Post Baseline value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values.
Measured: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in mmol/L: Potassium, Sodium, Chloride
Change=Post Baseline value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values.
Measured: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in Cell Counts: White Blood Cells (WBC), Total Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets
Change=Post Baseline value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values.
Measured: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline Red Blood Cell Count
Change=Post Baseline value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values.
Measured: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in mm/hr: Sedimentation Rate (ESR)
Change=Post Baseline value minus Baseline value. A positive difference reflects an increased laboratory parameter value over time; a negative difference reflects a decreased laboratory parameter value over time. Normal laboratory values depend on a subject age, gender, and the specific laboratory methods that were used to determine the lab values.
Measured: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score
The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a validated, physician-based assessment tool used to measure cutaneous lupus severity. Severity is calculated based on disease activity (erythema and scale) and damage (dyspigmentation and scarring) for the cumulative areas of involved skin. Severity categories based on the CLASI activity score are as follows: mild (0-9), moderate (10-20), and severe (21-70). A 4-point or 20% change in the CLASI activity score identifies a clinically meaningful change. A 4-point increase in the CLASI activity score indicates a flare.
Measured: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in SELENA-SLEDAI Total Score
The Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus (SLE) Disease Activity Index (SELENA-SLEDAI) score is a weighted scale score ranging from 0 to 105 based on the presence or absence of 24 manifestations of SLE. The SELENA-SLEDAI assesses disease activity for 10 days prior to and including the day of assessment. Positive change in the SELENA-SLEDAI score indicates increased disease activity.
Measured: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Patient's Global Assessment (PGA)
The global assessment (PGA) is a visual 3-inch analog scale from 0 to 3 in which the participant marks the scale according to perceived disease activity. A score of 0 corresponds to no lupus disease activity and a score of 3 corresponds to severe disease activity. A positive change from baseline indicates more disease activity.
Measured: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Physician's Global Assessment (PhGA)
The physician's global assessment (PhGA) is a visual analog 3-inch scale in the SELENA-SLEDAI that is scored from 0 to 3 by the physician. A score of 0 corresponds to no lupus disease activity and a score of 3 corresponds to severe disease activity. A positive change from baseline indicates more disease activity.
Measured: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Anti-dsDNA Antibody Titers
Double-stranded DNA is one of multiple diagnostic tests for SLE and high levels may be associated with disease activity. The positive range is based on the normal range from the local laboratory. A positive change from baseline value indicates the detection of autoantibodies to double-stranded DNA.
Measured: Baseline ( Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Serum C3 Complement Levels
C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 71 to 159 mg/dL. Those with active systemic lupus erythematosus (SLE) may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate SLE disease activity.
Measured: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Serum C4 Complement Levels
C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range is 13 to 30 mg/dL. Individuals with active systemic lupus erythematosus (SLE) may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity.
Measured: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2015 (estimated)
- Study start27 Aug 2015
- Primary completion2 Sep 2016
- Study completion3 Oct 2018
Why it stopped: Due to participant recruitment feasibility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lupus Erythematosus, CutaneousStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence
- Responsible party
- Sponsor
- Investigators
- Maria Dall'Era, MD, Study chair, University of California, San FranciscoAnna Haemel, MD, Study chair, University of California, San FranciscoJeffrey Bluestone, PhD, Study chair, University of California, San FranciscoMichael Rosenblum, MD, PhD, Study chair, University of California, San FranciscoDavid Wofsy, MD, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02428309
- Sponsor's protocol ID
- DAIT ALE08
- Status last verified
- Oct 2019
- First submitted
- 23 Apr 2015
- Last updated
- 12 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The plan is to share participant level data and additional relevant materials in the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts. Currently: study in progress-no data sharing.
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Dose Escalation Trial Exploring the Safety and Tolerability of Autologous Polyclonal Regulatory T Cell Therapy in Adults With Active Cutaneous Lupus (ALE08)
- ClinicalTrials.gov ID
- NCT02428309
- Acronym / sponsor ID
- DAIT ALE08
- Conditions
- Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic
- Keywords
- active cutaneous lupus, systemic lupus erythematosus (SLE), autologous polyclonal regulatory T cell Therapy, polyclonal Tregs for treatment of lupus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to participant recruitment feasibility
- Enrolment
- 1 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence
- Study start
- 27 Aug 2015 (actual)
- Primary completion
- 2 Sep 2016 (actual)
- Study completion
- 3 Oct 2018 (actual)
- First posted
- 28 Apr 2015 (estimated)
- Results
- Posted 12 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this Phase 1 study is to evaluate the safety, tolerability, and effect of 3 different doses of Treg therapy in adults with skin (cutaneous) involvement of their lupus. Targeting cutaneous disease offers the ability to control background therapy, readily detect clinical effects, and perform research analyses not only in blood but also skin. Safety, disease activity, and mechanism of Tregs will be evaluated. The intent is to support dose selection for a future larger efficacy trial in lupus.
Detailed description
The investigational therapy in this trial, regulatory T cells (Tregs), is evaluating an alternative to traditional immunosuppressive therapies for the treatment of systemic lupus erythematosus (SLE, lupus). Too frequently, aggressive therapies are inadequate in the control of the disease and have potent side effects and complications. The collection and expansion of one's own T cells harnesses a naturally occurring regulatory mechanism to restore self-tolerance in people with lupus. Tregs are a specialized subset of T cells that function to control the immune response. Studies have shown that in active lupus, the numbers and function of Treg cells are significantly decreased, which contributes to an overactive immune system and an increase in disease activity. The hope is that these naturally occurring Treg cells can be used for the treatment of autoimmune diseases, including lupus.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose Treg Cohort | Experimental | Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells3-6 participants will receive a single infusion of 1 x 10^ 8 autologous polyclonal Tregs (ex vivo selected and expanded) |
| Medium Dose Treg Cohort | Experimental | Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T CellsSequential dose escalation, 3-6 subjects will receive a single infusion of 4 x 10^ 8 autologous polyclonal Tregs (ex vivo selected and expanded) |
| High Dose Treg Cohort | Experimental | Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T CellsSequential dose escalation, 3-6 participants will receive a single infusion of 16 x 10^ 8 autologous polyclonal Tregs (ex vivo selected and expanded) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Ability to provide informed consent.
- Diagnosis of SLE by American College of Rheumatology (ACR) criteria or biopsy proven primary cutaneous lupus.
- Presence of ≥ 2 active cutaneous lupus lesions based on (1) visual morphology and (2) at least a grade 2 erythema on CLASI activity score. Histopathologic confirmation is required unless the active lesions are of the same morphology to previously histologically proven cutaneous lupus lesions.
- The cutaneous lupus lesions must include any of the following subtypes:
- Positive test for Epstein-Barr virus (EBV) antibody.
Key exclusion criteria (56 listed)
- New onset of cutaneous lupus which has not been treated with broad spectrum sunscreen (UVA and UVB) in combination with either antimalarials or another systemic medication for at least 3 months.
- Prednisone dose > 15mg/day within the 30 days prior to screening.
- Addition of a new medication, or change in the dose of any background medication, used to treat any aspect of SLE. Specifically:
- Doses of background medications at Screening visit:
- Intravenous immunoglobulin (IVIG), plasmapheresis, or leukopheresis within the 90 days prior to screening.
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 |
|---|---|---|
| Ex vivo Expanded Human Autologous Polyclonal Regulatory T CellsAlso: Ex vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells | Biological | High Dose Treg Cohort, Low Dose Treg Cohort, Medium Dose Treg Cohort |
Primary outcome
Number of Significant Adverse Events (AEs) Through Week 48
Time frame: From time of signed informed consent to Week 48
A significant adverse event is any related National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0 Grade 3 or higher AE or any related serious adverse event. Related is defined as being possibly, probably, or definitely related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.
19 secondary outcomes
Number of Significant Adverse Events (AEs) Through Week 152
Time frame: From time of signed informed consent to Week 152
Number of Grade 3 or Higher Adverse Events (AEs) Through Week 152
Time frame: From time of signed informed consent to Week 152
Number of Infection-Related Adverse Events (AEs) Through Week 152
Time frame: From time of signed informed consent to Week 152
Number of Lupus Flares Through Week 152 by Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Criteria
Time frame: From time of signed informed consent to Week 152
Number Infusion-Related Adverse Events (AEs) Within 24 Hours of Infusion
Time frame: From time of infusion to 24 hours post infusion
Change From Baseline: Alkaline Phosphatase (ALK), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)
Time frame: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in g/dL: Albumin, Hemoglobin
Time frame: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in mg/dL: Total Bilirubin, Creatinine
Time frame: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in mmol/L: Potassium, Sodium, Chloride
Time frame: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in Cell Counts: White Blood Cells (WBC), Total Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets
Time frame: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline Red Blood Cell Count
Time frame: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in mm/hr: Sedimentation Rate (ESR)
Time frame: Baseline (Visit 0) and Weeks 4, 12, 48, and 152
Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score
Time frame: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in SELENA-SLEDAI Total Score
Time frame: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Patient's Global Assessment (PGA)
Time frame: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Physician's Global Assessment (PhGA)
Time frame: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Anti-dsDNA Antibody Titers
Time frame: Baseline ( Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Serum C3 Complement Levels
Time frame: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Change From Baseline in Serum C4 Complement Levels
Time frame: Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
- Autoimmunity Centers of ExcellenceLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The plan is to share participant level data and additional relevant materials in the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts. Currently: study in progress-no data sharing.
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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.
Maria Dall'Era, MD study chair
University of California, San Francisco
Anna Haemel, MD study chair
University of California, San Francisco
Jeffrey Bluestone, PhD study chair
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells in people with Lupus Erythematosus, Cutaneous and Lupus Erythematosus, Discoid, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 10 inclusion and 56 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: stopped early, as of the sponsor's last update on 12 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Significant Adverse Events (AEs) Through Week 48 (time frame: From time of signed informed consent to Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Nov 2019.