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Neuromyelitis Optica Spectrum DisorderPhase 1NCT03605238

Treatment of Relapsed and/or Refractory AQP4-IgG Seropositive NMOSD by Tandem CAR T Cells Targeting CD19 and CD20

A Phase 1 study testing Corticosteroids & tanCART19/20 in people with Neuromyelitis Optica Spectrum Disorder, run by Chinese PLA General Hospital at 1 site in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

CAR-T therapy was proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Read more about this study

Who is it for?
Ages 12 to 75 years
Conditions the study is for
Neuromyelitis Optica Spectrum Disorder
What is being tested?
Corticosteroids & tanCART19/20
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteChina
Study dates
15 Aug 2018to 15 Aug 2020
Phase
Phase 1
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 12 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Clinical diagnosis of neuromyelitis optica spectrum disorders (NMOSD) patients.
  • Patients with AQP4-IgG seropositive by cell-based assay.
  • Patients with corticosteroid treatment combined immunosuppressant (azathioprine or mycophenolate mofetil or rituximab) still recurrence.
  • Clinical evidence of at least 2 relapses in last 12 months or 3 relapses in the last 24 months with at least 1 relapse in the 12 months prior to the Screening.
  • Best corrected visual acuity(BCVA)<20/60.
  • Normal bone marrow reserve function: neutrophils>1 500/mm3, Hemoglobin > 10g/dL, Platelet count > 100 000/mm3.
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  • Normal liver and kidney function: Creatinine < 2.5 mg/dl, ALT (alanine aminotransferase)/AST (aspartate aminotransferase) < 3x normal, Bilirubin < 2.0 mg/dl.
  • Successful test expansion of tanCART19/20 cells.
  • Adequate venous access for apheresis, and no other contraindications for leukapheresis.
  • Voluntary informed consent is given.

Who cannot join

  • Pregnant or lactating women (The safety of this therapy on unborn children is not known, Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion).
  • Any serious, uncontrolled diseases (including, but not limit to, uncontrolled active infection, active hepatitis B or hepatitis C infection, HIV infection, unstable angina pectoris, congestive heart failure, serious arrhythmia).
  • Concurrent use of systemic steroids or immunosuppressant in the last two weeks.
  • Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation.
  • Other patients who are not suitable for CAR-T therapy judged by the biotherapy physician.

Trial locations and contacts

1 site in 1 country.

China1 site

  • People's Liberation of Army General Hospital (PLAGH)

    Beijing, Beijing Municipality, 100853

Other trials in China

About this study

Official title: Clinical Study of CD19/CD20 tanCAR T Cells in Relapsed and/or Refractory AQP4-IgG Seropositive Neuromyelitis Optica Spectrum Disorders (NMOSD)

CAR-T therapy was proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Researchers only use it for the treatment of systemic lupus erythematosus (SLE). Neuromyelitis optica spectrum disorders (NMOSD), that include the neuromyelitis optica (NMO), are a group of inflammatory disorders of the central nervous system characterized by episodes of immune-mediated demyelination and axonal damage mainly involving optic nerves and spinal cord. NMO is characterized by the presence of an anti-Aquaporin-4 (AQP4) antibody, which can only be produced by differentiation of B cells to plasma cells. Because these anti-AQP4 antibodies may be pathogenic, B cells recognizing AQP4 may be directly involved in the disease process as well. B cells also play a role as potent antigen presenting cells in NMO. NMO has the characteristics of high recurrence rate and poor prognosis. In the conventional treatment options, NMOSD could be treated with corticosteroids and immunosuppressive drugs immunosuppressant (e.g. azathioprine, mycophenolate mofetil, rituximab). But these drugs could barely completely cure NMOSD. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The rationale for using CAR-T therapy in NMOSD is based on the known roles of B cells, antibody production and plasma cells in the pathophysiology of NMOSD. The strongest evidence of the importance of B cells in NMO comes from studies of B cell depletion, most commonly with anti-CD20 monoclonal antibody, rituximab. Emerging evidence indicates that peripheral B cells are activated during a relapse and plasmablast production of anti-AQP4 antibodies spikes. The investigators infuse tanCART19/20 to completely deplete B cells. The purpose of this study is to assess the safety and efficacy of this tanCART19/20 in the treatment of NMOSD.

Read the detailed description

This study is being conducted to assess anti-CD19/20 CAR T cells safety and efficacy in treating patients with AQP4-IgG seropositive NMOSD.

PRIMARY OBJECTIVES:

  1. To assess the safety of the tanCART-19/20 cells in treating NMOSD patients. II. Determine duration of in vivo survival of tanCART-19/20 cells.

SECONDARY OBJECTIVES:

  1. To assess the efficacy of the tanCART-19/20 cells in treating NMOSD patients.

II. The secondary outcome measures: annual relapse rate (ARR), Expanded Disability Status Scale Score(EDDS), Best Corrected Visual Acuity (Log MAR), Spectral-Domain Optical Coherence Tomography (SD-OCT), Flash Visual Evoked Potential (FVEP) and Immunological assessments.

OUTLINE: Patients receive anti-CD19/20-CAR (coupled with CD137 and CD3 zeta signalling domains) vector-transduced autologous T cells on days 0 in the absence of unacceptable toxicity. The infusion dose is 1E5-2E6 CAR positive T cells/kg, and dose escalation methods obey the traditional 3+3 design (three doses groups: 1-2E5, 3-6E5, 1-2E6 CAR-T cells).

After completion of study treatment, patients are followed intensively for 6 months, every 6 months for 2 years, and annually thereafter for 3 years.

Being tested
Corticosteroids & tanCART19/20
Keywords
Neuromyelitis Optica Spectrum Disorder, aquaporin4-IgG, CAR-T therapy
Medical subject headings
Neuromyelitis Optica

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Corticosteroids & tanCART19/20Biological

    Twelve days of high-dose IV methylprednisolone (1000mg×3 days, 500mg×3 days, 240mg×3 days, 120mg×3 days) before anti-CD19/20 CAR T cells infusion. The dose is 1E5~2E6 anti-CD19/20-CAR positive T cells. The cells infusion process may last for 30 min.

Study groups in NCT03605238
Study groupRoleWhat they receive
Corticosteroids & tanCART19/20ExperimentalTwelve days of high-dose IV methylprednisolone to reduce acute inflammation, then infuse anti-CD19/20-CAR retroviral vector-transduced autologous derived T cells only once.
Receives: Biological: Corticosteroids & tanCART19/20

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Occurrence of study related adverse events

    defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment.

    Measured: From baseline to 12 months after

Secondary outcomes (6)

  1. Annualized relapse rate (ARR) of NMOSD Attacks

    Compare annualized relapse rate before and one year after initial CAR-T administration.

    Measured: Baseline, 12 months

  2. Change in Expanded Disability Status Scale (EDDS) Score

    The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death) in half-point increments.

    Measured: Baseline, 12 months

  3. Change in Best Corrected Visual Acuity (Log MAR)

    Visual acuity assessment through Snellen's test chart.

    Measured: Baseline, 12 months

  4. Change in peripapillary retinal nerve fibre layer(pRNFL)

    Compared pRNFL before and one year after initial CAR-T administration.

    Measured: Baseline, 12 months

  5. Change in macular ganglion cell-inner plexiform layers (mGCIPL)

    Compared mGCIPL before and one year after initial CAR-T administration.

    Measured: Baseline, 12 months

  6. Change in Flash Visual Evoked Potential (FVEP)

    Compared FVEP before and one year after initial CAR-T administration.

    Measured: Baseline, 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2018
  2. Study start15 Aug 2018 (estimated)
  3. Primary completion15 Aug 2019 (estimated)
  4. Study completion15 Aug 2020 (estimated)

Why it stopped: It was hard to recruit patients

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03605238
Sponsor's protocol ID
CHN-PLAGH-NO-S2018-002-02
Status last verified
Aug 2019
First submitted
29 Jun 2018
Last updated
19 Sep 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Corticosteroids & tanCART19/20 in people with Neuromyelitis Optica Spectrum Disorder, run by Chinese PLA General Hospital at 1 site in China.

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 5 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: withdrawn, as of the sponsor's last update on 19 Sep 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 China. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Occurrence of study related adverse events (time frame: From baseline to 12 months after). 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 NCT03605238.

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 19 Sep 2019.

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