Systemic SclerosisPhase 1NCT06414135
Relmacabtagene Autoleucel for the Treatment of Systemic Sclerosis
A Phase 1 study testing Relma-cel in people with Systemic Sclerosis, run by Liangjing Lu at 1 site in China.
Trial summary
Relma-cel is a product containing CD19-CAR-transduced T cells. The purpose of this study is to evaluate the safety of Relma-cel at different dose levels in patients with early diffuse systemic sclerosis. Efficacy will be explored too. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Systemic Sclerosis
- What is being tested?
- Relma-cel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 12 Jun 2024to Apr 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- voluntary to sign the ICF
- aged between 18-65 years old (inclusive)
- diagnosed with diffuse systemic sclerosis according to 2013 ACR Systemic Sclerosis Classification Criterion
- meet the definitions of refractory/progressive as below:
- refractory: non-respondent to or disease recurrence after remission with conventional therapies. Conventional therapies are defined as treated for more than 6 months with low dose steroids (≤ 15 mg prednisone equivalent), cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporin or biologics such as rituximab, belimumab, telitacicept, tocilizumab;
- progressive: having below manifestations within 6 months
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- mRSS increases by >= 3
- FVC decreases by > 10% or FVC decreases by > 5% and DLCO decreases by > 15%
- without systemic active infections within 2 weeks of leukapheresis, e.g., infectious pneumonia, tuberculosis
- available vascular access for leukapheresis
- major organ functions:
- Renal function: CrCl ≥50 ml/min (Cockcroft/Gault equation)
- Bone marrow function: ANC ≥ 1000/uL, absolute lymphocyte count ≥100/uL, Hb ≥90 g/L, Platelet count ≥75 x 10^9/L. Blood transfusion and infusion of growth factors within 7 days of eligibility assessment are not allowed.
- Liver function: ALT ≤ 3 x ULN, AST ≤ 3 x ULN, total bilirubin ≤ 2 x ULN (in case of Gilbert syndrome, total bilirubin ≤ 3 x ULN)
- Coagulation: INR ≤ 1.5 x ULN, PT ≤1.5 x ULN
- Cardiac function: LVEF ≥ 55%
- negative result of serum β-hCG measurement for women of childbearing potential at screening and within 48 hours of the first dose of lymphodepletion
- Female subjects with childbearing potential or male subjects with partners of childbearing potential should adopt medically effective contraception or abstinence from enrollment to 2 years after the end of the study; female subjects with childbearing potential should have a negative serum hCG test within 7 days of enrollment and not in lactation
Who cannot join
- NYHA class IV
- FVC predicted < 45% or DLCO predicted < 40%
- abnormalities on HRCT not attributable to systemic sclerosis
- history of autologous stem cell transplantation
- with manifestations of renal crisis
- with other autoimmune comorbidities that need systemic treatment
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- with a history of severe drug allergy
- with congenital immunoglobulin deficiency
- with malignant tumors, except for nonmelanoma skin cancer, in situ cervical cancer, bladder cancer, breast cancer which has been disease free for more than 2 years
- with psychiatric diseases or severe cognition dysfunctions
- within 5 half-life cycles of the last administration of an investigational product
- pregnant, lactation or plan to be pregnant within one year
- a history of CAR-T therapy or other gene-modified T cell targeted therapies
- other conditions that are not suitable for enrollment of the study in the judgement of the investigator
- the use of any live vaccines against infections within one month of the screening
- with any manifestations of active tuberculosis at screening
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, 200001
Liangjing Lu, 86-13661472001, Lu_liangjing@163.com
About this study
Official title: A Dose Ranging Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Pharmacodynamics of Relmacabtagene Autoleucel (Relma-cel) in Patients With Refractory/Progressive Systemic Sclerosis
Relma-cel is a product containing CD19-CAR-transduced T cells. The purpose of this study is to evaluate the safety of Relma-cel at different dose levels in patients with early diffuse systemic sclerosis. Efficacy will be explored too. If enrolled, participants will undergo leukapheresis, lymphodepleting chemotherapy and administration of Relma-cel.
- Conditions
- Systemic Sclerosis
- Being tested
- Relma-cel
- Keywords
- CAR-T cell therapy, systemic sclerosis, B cell depletion
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Relma-celBiological
All participants will receive Relma-cel once at different dose levels: 25×10^6 CAR+ T cells、50×10^6 CAR+ T cells、75×10^6 CAR+ T cells
| Study group | Role | What they receive |
|---|---|---|
| Relma-cel arm | Experimental | All participants will receive Relma-cel once at different dose levels Receives: Biological: Relma-cel |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT rate
the incidence of dose-limiting toxicity
Measured: 28 days
Occurrence of AEs and SAEs
frequency and severity of AEs and SAEs
Measured: 3 months
Secondary outcomes (16)
Relma-cel cell numbers and transgene copy numbers and duration in blood
Normally Relma-cel number and transgene copy number will gradually decrease to non-measurable as time goes on.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the changes of CD19+ cells and other B cell subsets
Theoretically the number of CD19+ cells and other B cell subsets will significantly decreased following Relma-cel administration and gradually increase to normal level as the effect of Relma-cel disappear
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in Composite Response Index in Systemic Sclerosis (CRISS)
Criss is an indicator to evaluate the efficacy of systemic sclerosis therapies. A score greater than or equal to 0.6 means Improvement. A score less than 0.6 means No Improvement.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in Sclerodema Clinical Trial Consortium-Damage Index (SCTC-DI)
SCTC-DI is a 23-item questionnaire to evaluate the organ damage in patients with systemic sclerosis. The range is between 0-55. The higher the score is, the worse the damage is.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in modified Rodnan Skin Score (mRSS)
mRSS is an instrument to evaluate cutaneous involvement in patients with systemic sclerosis. The total score ranges from 0 to 51. The higher the score is, the more the cutaneous involvement is.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in pulmonary function (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO))
The two items are used to evaluate pulmonary function. Normally both indicators should be greater than 80%.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in cardiac function (left ventricular ejection fraction, LVEF)
LVEF is an indicator of the heart's ability to eject blood out. The normal range is 50-55%
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in high resolution computed tomography (HRCT)
HRCT is a radiology test of the lungs. In this trial, HRCT will be used to evaluate the lesion size of the lungs, e.g., a lesion could be 10% of the lungs. The greater the percentage is, the worse the lesion is.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in disease activity score -28 (DAS-28) if any joint involvement
DAS-28 is a questionnaire to evaluate disease activity in patients with rheumatoid arthritis. 28 joints will be evaluated. Less than 2.6 means the disease is in remission. 2.6-3.2 means a low disease activity. More than 3.2 means active disease needing change in medication. More than 5.1 means very active disease that requires careful monitoring and adjustment to medication
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in the levels of inflammation biomarkers including C-reactive protein (CRP), erythropoietin sedimentation rate (ESR) and ferritin
CRP, ESR and ferritin are inflammation biomarkers. The normal ranges are different in different labs. Higher values than the upper limit of normal range mean the presence of inflammation.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
systemic sclerosis specific antibodies, e.g., anti-scl-70 antibodies, anti-RNA polymerase III antibodies, anti-centrosome antibodies, antinuclear antibody (ANA)
Normally all the antibodies are negative in human body. A positive result means abnormalities of immune system.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in skin biopsy pathology, e.g., the number of lymphocytes, the thickness of epiderm
In the presence of systemic sclerosis, the increased number of T and B lymphocytes, the thinning of epiderm and the decreased number of sweat gland are expected.
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in nailfold capillaroscopy examination, e.g., the capillary density, the diameter of capillaries
nailfold capillaroscopy is a device to observe the capillaries in the nailfold areas. With system sclerosis, the capillary density will diminish and expanded capillary loop may occur
Measured: 12 months
the change from baseline in skin stiffness (measuring the thickness of epiderm and dermis) by skin ultrasound
the thickness of epiderm and dermis will be thinner in the presence of systemic sclerosis.
Measured: 12 months
the change from baseline in health assessment questionnaire -damage index (HAQ-DI)
HAQ-DI, assesses a patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asks over the past week "Are you able to …" perform a particular task. The patient's responses are made on a scale from zero (no disability) to three (completely disabled). The total score will be 0-3. The higher the score is, the worse the body function is.
Measured: 12 months
the change from baseline in IgG, IgM, IgE, IgA
with Relma-cel administration, IgG, IgM, IgE, IgA will significantly decrease, then graduallly increase as the effect of Relma-cel disappears
Measured: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start12 Jun 2024
- Primary completionMay 2025 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liangjing Lu
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Ming Ju Biotechnology Co., Ltd.
- Responsible party
- Sponsor-investigator, Liangjing Lu, RenJi Hospital
- Investigators
- Liangjing Lu, Study chair, RenJi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06414135
- Sponsor's protocol ID
- JWCAR029029
- Status last verified
- Aug 2024
- First submitted
- 6 May 2024
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Ranging Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Pharmacodynamics of Relmacabtagene Autoleucel (Relma-cel) in Patients With Refractory/Progressive Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT06414135
- Acronym / sponsor ID
- JWCAR029029
- Conditions
- Systemic Sclerosis
- Keywords
- CAR-T cell therapy, systemic sclerosis, B cell depletion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Liangjing LuUniversity, hospital or other
- Collaborators
- Shanghai Ming Ju Biotechnology Co., Ltd.
- Study start
- 12 Jun 2024 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 16 May 2024 (actual)
- 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.
Relma-cel is a product containing CD19-CAR-transduced T cells. The purpose of this study is to evaluate the safety of Relma-cel at different dose levels in patients with early diffuse systemic sclerosis. Efficacy will be explored too. If enrolled, participants will undergo leukapheresis, lymphodepleting chemotherapy and administration of Relma-cel.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Relma-cel arm | Experimental | Biological: Relma-celAll participants will receive Relma-cel once at different dose levels |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- voluntary to sign the ICF
- aged between 18-65 years old (inclusive)
- diagnosed with diffuse systemic sclerosis according to 2013 ACR Systemic Sclerosis Classification Criterion
- meet the definitions of refractory/progressive as below:
- without systemic active infections within 2 weeks of leukapheresis, e.g., infectious pneumonia, tuberculosis
Key exclusion criteria (16 listed)
- NYHA class IV
- FVC predicted < 45% or DLCO predicted < 40%
- abnormalities on HRCT not attributable to systemic sclerosis
- history of autologous stem cell transplantation
- with manifestations of renal crisis
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 |
|---|---|---|
| Relma-celAll participants will receive Relma-cel once at different dose levels: 25×10^6 CAR+ T cells、50×10^6 CAR+ T cells、75×10^6 CAR+ T cells | Biological | Relma-cel arm |
Primary outcome
DLT rate
Time frame: 28 days
the incidence of dose-limiting toxicity
Occurrence of AEs and SAEs
Time frame: 3 months
frequency and severity of AEs and SAEs
16 secondary outcomes
Relma-cel cell numbers and transgene copy numbers and duration in blood
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the changes of CD19+ cells and other B cell subsets
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in Composite Response Index in Systemic Sclerosis (CRISS)
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in Sclerodema Clinical Trial Consortium-Damage Index (SCTC-DI)
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in modified Rodnan Skin Score (mRSS)
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in pulmonary function (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO))
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in cardiac function (left ventricular ejection fraction, LVEF)
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in high resolution computed tomography (HRCT)
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in disease activity score -28 (DAS-28) if any joint involvement
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in the levels of inflammation biomarkers including C-reactive protein (CRP), erythropoietin sedimentation rate (ESR) and ferritin
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
systemic sclerosis specific antibodies, e.g., anti-scl-70 antibodies, anti-RNA polymerase III antibodies, anti-centrosome antibodies, antinuclear antibody (ANA)
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in skin biopsy pathology, e.g., the number of lymphocytes, the thickness of epiderm
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in nailfold capillaroscopy examination, e.g., the capillary density, the diameter of capillaries
Time frame: 12 months
the change from baseline in skin stiffness (measuring the thickness of epiderm and dermis) by skin ultrasound
Time frame: 12 months
the change from baseline in health assessment questionnaire -damage index (HAQ-DI)
Time frame: 12 months
the change from baseline in IgG, IgM, IgE, IgA
Time frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
- Individual participant dataSharing planned: No
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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.
Liangjing Lu study chair
RenJi Hospital
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 Relma-cel in people with Systemic Sclerosis, run by Liangjing Lu 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 18 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 15 Aug 2024. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Liangjing Lu (86-13661472001, Lu_liangjing@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT rate (time frame: 28 days). The study lists 2 primary outcomes in all. 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 15 Aug 2024.