Severe Systemic SclerosisPhase 1/2MSC-AT-SScNCT06722105
Phase I/II Randomized Clinical Trial of Allogeneic Adipose Tissue-derived Mesenchymal Stromal Cells Systemic Infusion in Severe Systemic Sclerosis
A Phase 1/2 study testing 2 infusions of MSC and 1 infusion of MSC in people with Severe Systemic Sclerosis, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Systemic sclerosis (SSc) is a rare, severe and chronic systemic autoimmune disease (AD) characterized by vasculopathy, immune dysregulation and fibrosis leading to multi-organ dysfunction (primarily skin, lungs, heart gastrointestinal tract and kidneys), with high morbidity and mortality, altered health-related… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Severe Systemic Sclerosis
- What is being tested?
- 2 infusions of MSC and 1 infusion of MSC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2024to 1 May 2027
- Phase
- Phase 1/2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide signed and dated informed consent;
- Willing to comply with all study procedures and be available for the duration of the study;
- Male or female, aged ≥ 18 and ≤ 70 years of age
- SSc patients according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2013 classification criteria for SSc
- Severe disease with either:
- disease duration of 2 years or less with a modified Rodnan skin score (mRss) ≥ 20 and (abnormal CRP > 5 mg/l and/or hemoglobin < 11 g/dL), or
Show all 15Show fewer
- mRSS ≥ 15 without any restriction as to disease duration plus at least one major organ involvement as defined by:
- respiratory involvement consisting of lung diffusion capacity for carbon monoxide (DLCO) and/or forced vital capacity (FVC) < 80% predicted and evidence of interstitial lung disease : bronchiolar involvement, areas of ground-glass contusions or fibrosis (chest X-ray and/or high resolution computed tomography (HRCT) scan) and/or moderate Pulmonary hypertension with baseline resting systolic pulmonary arterial pressures > 35 mmHg and below 50 mmHg by cardiac echocardiography, or mean pulmonary artery pressure > 20 mmHg and < 40 mm Hg on right heart catheterization;
- renal involvement consisting of past renal crisis, microangiopathic hemolytic anemia, and/or renal insufficiency not explained by other causes than SSc;
- cardiac involvement consisting of reversible congestive heart failure, atrial or ventricular rhythm disturbances such as recurrent episodes of atrial fibrillation or flutter, recurrent atrial paroxysmal tachycardia, 2nd or 3rd degree AV-block, mild to moderate pericardial effusion and/or presence of MRI involvement (Increased T1 or T2 mapping, late gadolinium enhancement, septal D sign). All causes of organ involvement should be attributed to SSc.
- Contraindication, inadequate response or unwillingness to undergo AHSCT(determined by patient and physician judgement)
- Contraindication, inadequate response or unwillingness or adverse events necessitating discontinuation of conventional immunosuppressive therapy (MMF, methotrexate);
- Women of reproductive potential must use highly effective contraception;
- Men of reproductive potential must use condoms;
- Health insurance.
Who cannot join
- Age < 18 years and > 70 years
- Pregnancy or unwillingness to use adequate contraception;
- Life-threatening end-organ damage defined as: DLCO (corrected for hemoglobin) < 30% predicted; Left ventricular ejection fraction < 40% by cardiac echocardiography; Pulmonary hypertension with baseline resting systolic pulmonary arterial pressures > 50 mmHg by cardiac echocardiography, or mean pulmonary artery pressure > 40 mmHg on right heart catheterization; glomerular filtration rate < 30mL/min
- Active Hepatitis (ASAT, ALAT > 3 normal)
- Neoplasms of less than 5 years, except for basal cell or in situ cervix carcinoma or concurrent myelodysplasia,
- Uncontrolled hypertension
Show all 14Show fewer
- Uncontrolled acute or chronic infection
- HIV-1 or HIV-2 infection
- Body Mass Index < 16.5 kg/m2
- Severe psychiatric disorder
- Bone marrow insufficiency, defined as neutropenia < 1 x 109/L, thrombopenia < 50 x 109/L, anemia < 8 g/dL, lymphopenia < 0,5 x 109/L
- Inability to provide informed consent
- Patient included in another interventional clinical trial
- Patient under tutelle
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Systemic sclerosis (SSc) is a rare, severe and chronic systemic autoimmune disease (AD) characterized by vasculopathy, immune dysregulation and fibrosis leading to multi-organ dysfunction (primarily skin, lungs, heart gastrointestinal tract and kidneys), with high morbidity and mortality, altered health-related quality of life, all at high cost for patients and society.
Treatment are mostly symptomatic and only autologous hematopoietic stem cell transplantation (AHSCT) has shown long term improvement in overall and event-free survival with disease-modifying properties. However, AHSCT is contra-indicated in case of advanced visceral involvement and in eligible patients, it is still associated with risk of toxicity. There is an urgent need to identify safe and effective treatments for severe SSc.
Read more
Mesenchymal stromal cells (MSC) are multipotent cells which carry immunomodulatory, pro-angiogenic and anti-fibrotic properties, that can target SSc pathogenesis and its clinical manifestations. The increasing use of MSC, harvested from bone marrow (MSC(M)), adipose tissue (MSC(AT)), or umbilical cord (MSC(UC)) in a variety of indications, provides consistent evidence supporting their safety in humans. The efficacy of MSC(M) intravenous (IV) injection for treating acute graft versus host disease led to their marketing approval in 2012 and MSC(AT) (Alofisel) were approved for severe Crohn's fistula in 2018.
MSC represent a promising therapeutic approach for SSc. We have previously a) shown disease-specific abnormalities in MSC(M) from SSc patients, providing strong rationale to use allogeneic MSC to treat SSc patients, b) published the first phase I/II dose escalation trial using allogenic MSC(M) infusion in 20 severe SSc patients (ClinicalTrials.gov: NCT02213705, PHRC AOM 11-250) with no safety issues, significant improvement in skin fibrosis at 3 to 6 months after infusion which appeared lower thereafter, thereby supporting the need for repeated infusions.
In vitro, experimental and clinical studies suggest that MSC properties vary according to their tissue of origin/source. We demonstrated that compared to MSC(M), MSC(AT) are easier to harvest and display higher proliferative capability before entering senescence, higher genetic stability, and superior immunosuppressive properties.
Considering the above rationale, we hypothesize that use of healthy donors allogeneic MSC(AT) produced by Etablissement Français du Sang (EFS) will demonstrate a) no safety issues, b) an efficacy profile that will increase with repeated infusion of allogeneic MSC(AT) to treat SSc.
- Conditions
- Severe Systemic Sclerosis
- Being tested
- 2 infusions of MSC, 1 infusion of MSC, Placebo
- Keywords
- Systemic autoimmune disease, Allogenic mesenchymal stromal cells infusion
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2 infusions of MSCBiological
1 MSC(AT) (2x10^6 cells/kg) injection at M0 and 1 MSC(AT) (2x10^6 cells/kg) injection at M3
1 infusion of MSCBiological
1 MSC(AT) (2x10^6 cells/kg) injection at M0 and 1 placebo injection at M3
PlaceboOther
Placebo at M0 and M3
| Study group | Role | What they receive |
|---|---|---|
| 2 infusions of MSC | Experimental | Not described Receives: Biological: 2 infusions of MSC |
| 1 infusion of MSC | Experimental | Not described Receives: Biological: 1 infusion of MSC |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of treatment-related Serious Adverse Events
Defined as Adverse Events (AE) of grade equal or above 3 using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification, at one month after each infusion according to arms (M1, M4) An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3
Measured: After each infusion
Secondary outcomes (45)
Rate of treatment-related Serious Adverse Events (SAE)
Adverse Events of grade equal or above 3 CTCAE v5.0 An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3
Measured: At time of infusion
Rate of treatment-related Serious Adverse Events (SAE)
Adverse Events of grade equal or above 3 CTCAE v5.0 An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3
Measured: Within 24 hours of infusion
Rate of treatment-related Serious Adverse Events (SAE)
Adverse Events of grade equal or above 3 CTCAE v5.0 An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3
Measured: At 6 months
Rate of treatment-related Serious Adverse Events (SAE)
Adverse Events of grade equal or above 3 CTCAE v5.0 An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3
Measured: At 9 months
Rate of treatment-related Serious Adverse Events (SAE)
Adverse Events of grade equal or above 3 CTCAE v5.0 An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3
Measured: At 12 months
Mean modified Rodnan skin score (mRSS) difference
Main efficacy endpoint is assessed by mRSS difference between M0 and M12 Mean modified Rodnan skin score (mRSS) is a semiquantitative score, ranging from 0 (normal) to 3 (severe), used to evaluate the skin thickness in 17 different cutaneous sites (for a total score from 0 to 51). The higher the score, the more severe the disease.
Measured: Between Month 0 and month 12
Mean modified Rodnan skin score (mRSS)
Mean modified Rodnan skin score (mRSS) is a semiquantitative score, ranging from 0 (normal) to 3 (severe), used to evaluate the skin thickness in 17 different cutaneous sites (for a total score from 0 to 51). The higher the score, the more severe the disease.
Measured: At 3 months
Mean modified Rodnan skin score (mRSS)
Mean modified Rodnan skin score (mRSS) is a semiquantitative score, ranging from 0 (normal) to 3 (severe), used to evaluate the skin thickness in 17 different cutaneous sites (for a total score from 0 to 51). The higher the score, the more severe the disease.
Measured: At 6 months
WHO performance status
Karnofsky performance scale Score varies betwwen 0 and 5. The lower the score, the less the patient's life is affected.
Measured: At month 0
WHO performance status
Karnofsky performance scale Score varies betwwen 0 and 5. The lower the score, the less the patient's life is affected.
Measured: At month 3
WHO performance status
Karnofsky performance scale Score varies betwwen 0 and 5. The lower the score, the less the patient's life is affected.
Measured: At month 6
WHO performance status
Karnofsky performance scale Score varies betwwen 0 and 5. The lower the score, the less the patient's life is affected.
Measured: At month 12
Scleroderma-Health Assessment Quetionnaire
It determines a disability index (DI), which is calculated as a continuous variable from 0 (no disability) to 3 (severe disability) Steen VA Arthritis et rhumatism 1997 ; 40 : 1984-91
Measured: At month 0
Scleroderma-Health Assessment Quetionnaire
It determines a disability index (DI), which is calculated as a continuous variable from 0 (no disability) to 3 (severe disability) Steen VA Arthritis et rhumatism 1997 ; 40 : 1984-91
Measured: At month 3
Scleroderma-Health Assessment Quetionnaire
It determines a disability index (DI), which is calculated as a continuous variable from 0 (no disability) to 3 (severe disability) Steen VA Arthritis et rhumatism 1997 ; 40 : 1984-91
Measured: At month 6
Scleroderma-Health Assessment Quetionnaire
It determines a disability index (DI), which is calculated as a continuous variable from 0 (no disability) to 3 (severe disability) Steen VA Arthritis et rhumatism 1997 ; 40 : 1984-91
Measured: At month 12
Short Form (36) health survey (SF36v2)
The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.
Measured: At month 0
Short Form (36) health survey (SF36v2)
The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.
Measured: At month 3
Short Form (36) health survey (SF36v2)
The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.
Measured: At month 6
Short Form (36) health survey (SF36v2)
The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.
Measured: At month 12
EQ-5D-5L quality of life questionnaire
It evaluates five dimensions : mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has five levels : no problems, slight problems, moderate problems, severe problems and extreme problems. Answers are given on a 5-point scale by domain, the higher the score, the poorer the quality of life.
Measured: At month 0
EQ-5D-5L quality of life questionnaire
It evaluates five dimensions : mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has five levels : no problems, slight problems, moderate problems, severe problems and extreme problems. Answers are given on a 5-point scale by domain, the higher the score, the poorer the quality of life.
Measured: At month 3
EQ-5D-5L quality of life questionnaire
It evaluates five dimensions : mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has five levels : no problems, slight problems, moderate problems, severe problems and extreme problems. Answers are given on a 5-point scale by domain, the higher the score, the poorer the quality of life.
Measured: At month 6
EQ-5D-5L quality of life questionnaire
It evaluates five dimensions : mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has five levels : no problems, slight problems, moderate problems, severe problems and extreme problems. Answers are given on a 5-point scale by domain, the higher the score, the poorer the quality of life.
Measured: At month 12
Forced Vital Capacity (FVC)
Measured: At month 0
Forced Vital Capacity (FVC)
Measured: At month 3
Forced Vital Capacity (FVC)
Measured: At month 6
Forced Vital Capacity (FVC)
Measured: At month 12
Diffusing capacity of Lung for carbon monoxide (DLCO)
Measured: At month 0
Diffusing capacity of Lung for carbon monoxide (DLCO)
Measured: At month 3
Diffusing capacity of Lung for carbon monoxide (DLCO)
Measured: At month 6
Diffusing capacity of Lung for carbon monoxide (DLCO)
Measured: At month 12
Response to treatment
Defined as any of the following: decreased mRss > 25%, increased FVC > 10% and/or increased DLCO >10%, without need for further immunosuppression except low dose steroids (below 10mg daily)
Measured: At month 3
Response to treatment
Defined as any of the following: decreased mRss > 25%, increased FVC > 10% and/or increased DLCO >10%, without need for further immunosuppression except low dose steroids (below 10mg daily)
Measured: At month 6
Response to treatment
Defined as any of the following: decreased mRss > 25%, increased FVC > 10% and/or increased DLCO >10%, without need for further immunosuppression except low dose steroids (below 10mg daily)
Measured: At month 12
Progression Free Survival
Defined as the percentage of enrolled patients still alive without evidence of progression 12 months after MSC(AT) injection, with progression defined as any of the following compared to baseline evaluation: decreased FVC > 10% or DLCO > 15%; decrease in LVEF% > 15%; decrease in weight > 15%; decrease in creatinine clearance > 30%; increased mRss > 25% ; and/or increase in SHAQ> 0.5
Measured: At month 12
Global Rank Composite Score (GRCS)
GRCS is based on several outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure , renal failure , or cardiac failure . The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline.
Measured: At month 3
Global Rank Composite Score (GRCS)
GRCS is based on several outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure , renal failure , or cardiac failure . The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline.
Measured: At month 6
Global Rank Composite Score (GRCS)
GRCS is based on several outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure , renal failure , or cardiac failure . The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline.
Measured: At month 12
Composite response index in dcSSc (CRISS)
For early SSc patients only It is a weighted score and includes five measures: modified Rodnan skin score, FVC% predicted, HAQ-DI, patient and clinician global assessments.
CRISS score is a probability from 0 to 1 that represents the likelihood of a patient achieving overall improvement. The higher the score, the greater the improvement
Measured: At month 3
Composite response index in dcSSc (CRISS)
For early SSc patients only It is a weighted score and includes five measures: modified Rodnan skin score, FVC% predicted, HAQ-DI, patient and clinician global assessments.
CRISS score is a probability from 0 to 1 that represents the likelihood of a patient achieving overall improvement. The higher the score, the greater the improvement.
Measured: At month 6
Composite response index in dcSSc (CRISS)
For early SSc patients only
Measured: At month 12
Overall survival
For early SSc patients only It is a weighted score and includes five measures: modified Rodnan skin score, FVC% predicted, HAQ-DI, patient and clinician global assessments.
CRISS score is a probability from 0 to 1 that represents the likelihood of a patient achieving overall improvement. The higher the score, the greater the improvement
Measured: At month 12
Impact of allogeneic MSC(AT) infusion on the immune response
Impact of allogeneic MSC(AT) iv once or twice at 3 months interval on the immune response, including immunophenotyping and alloimmunization up to M6 after starting therapy
Measured: Up to 6 months
Cost effectiveness of the allogeneic MSC(AT) infusion
Once or twice versus no treatment in severe SSc
Measured: At month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2024
- Study start1 Dec 2024 (estimated)
- Primary completion1 Apr 2026 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Systemic SclerosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Model description
- Multi-center, three-arm, randomized, double-blind, placebo-controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06722105
- Sponsor's protocol ID
- APHP211026
- Acronym
- MSC-AT-SSc
- Status last verified
- Nov 2024
- First submitted
- 3 Dec 2024
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Randomized Clinical Trial of Allogeneic Adipose Tissue-derived Mesenchymal Stromal Cells Systemic Infusion in Severe Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT06722105
- Acronym / sponsor ID
- MSC-AT-SSc / APHP211026
- Conditions
- Severe Systemic Sclerosis
- Keywords
- Systemic autoimmune disease, Allogenic mesenchymal stromal cells infusion
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- 1 Apr 2026 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 9 Dec 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.
Systemic sclerosis (SSc) is a rare, severe and chronic systemic autoimmune disease (AD) characterized by vasculopathy, immune dysregulation and fibrosis leading to multi-organ dysfunction (primarily skin, lungs, heart gastrointestinal tract and kidneys), with high morbidity and mortality, altered health-related quality of life, all at high cost for patients and society.
Treatment are mostly symptomatic and only autologous hematopoietic stem cell transplantation (AHSCT) has shown long term improvement in overall and event-free survival with disease-modifying properties. However, AHSCT is contra-indicated in case of advanced visceral involvement and in eligible patients, it is still associated with risk of toxicity. There is an urgent need to identify safe and effective treatments for severe SSc.
Mesenchymal stromal cells (MSC) are multipotent cells which carry immunomodulatory, pro-angiogenic and anti-fibrotic properties, that can target SSc pathogenesis and its clinical manifestations. The increasing use of MSC, harvested from bone marrow (MSC(M)), adipose tissue (MSC(AT)), or umbilical cord (MSC(UC)) in a variety of indications, provides consistent evidence supporting their safety in humans. The efficacy of MSC(M) intravenous (IV) injection for treating acute graft versus host disease led to their marketing approval in 2012 and MSC(AT) (Alofisel) were approved for severe Crohn's fistula in 2018.
MSC represent a promising therapeutic approach for SSc. We have previously a) shown disease-specific abnormalities in MSC(M) from SSc patients, providing strong rationale to use allogeneic MSC to treat SSc patients, b) published the first phase I/II dose escalation trial using allogenic MSC(M) infusion in 20 severe SSc patients (ClinicalTrials.gov: NCT02213705, PHRC AOM 11-250) with no safety issues, significant improvement in skin fibrosis at 3 to 6 months after infusion which appeared lower thereafter, thereby supporting the need for repeated infusions.
In vitro, experimental and clinical studies suggest that MSC properties vary according to their tissue of origin/source. We demonstrated that compared to MSC(M), MSC(AT) are easier to harvest and display higher proliferative capability before entering senescence, higher genetic stability, and superior immunosuppressive properties.
Considering the above rationale, we hypothesize that use of healthy donors allogeneic MSC(AT) produced by Etablissement Français du Sang (EFS) will demonstrate a) no safety issues, b) an efficacy profile that will increase with repeated infusion of allogeneic MSC(AT) to treat SSc.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Multi-center, three-arm, randomized, double-blind, placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| 2 infusions of MSC | Experimental | Biological: 2 infusions of MSC |
| 1 infusion of MSC | Experimental | Biological: 1 infusion of MSC |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Provide signed and dated informed consent;
- Willing to comply with all study procedures and be available for the duration of the study;
- Male or female, aged ≥ 18 and ≤ 70 years of age
- SSc patients according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2013 classification criteria for SSc
- Severe disease with either:
Key exclusion criteria (14 listed)
- Age < 18 years and > 70 years
- Pregnancy or unwillingness to use adequate contraception;
- Life-threatening end-organ damage defined as: DLCO (corrected for hemoglobin) < 30% predicted; Left ventricular ejection fraction < 40% by cardiac echocardiography; Pulmonary hypertension with baseline resting systolic pulmonary arterial pressures > 50 mmHg by cardiac echocardiography, or mean pulmonary artery pressure > 40 mmHg on right heart catheterization; glomerular filtration rate < 30mL/min
- Active Hepatitis (ASAT, ALAT > 3 normal)
- Neoplasms of less than 5 years, except for basal cell or in situ cervix carcinoma or concurrent myelodysplasia,
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 |
|---|---|---|
| 2 infusions of MSC1 MSC(AT) (2x10^6 cells/kg) injection at M0 and 1 MSC(AT) (2x10^6 cells/kg) injection at M3 | Biological | 2 infusions of MSC |
| 1 infusion of MSC1 MSC(AT) (2x10^6 cells/kg) injection at M0 and 1 placebo injection at M3 | Biological | 1 infusion of MSC |
| PlaceboPlacebo at M0 and M3 | Other | Placebo |
Primary outcome
Rate of treatment-related Serious Adverse Events
Time frame: After each infusion
Defined as Adverse Events (AE) of grade equal or above 3 using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification, at one month after each infusion according to arms (M1, M4) An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3
45 secondary outcomes
Rate of treatment-related Serious Adverse Events (SAE)
Time frame: At time of infusion
Rate of treatment-related Serious Adverse Events (SAE)
Time frame: Within 24 hours of infusion
Rate of treatment-related Serious Adverse Events (SAE)
Time frame: At 6 months
Rate of treatment-related Serious Adverse Events (SAE)
Time frame: At 9 months
Rate of treatment-related Serious Adverse Events (SAE)
Time frame: At 12 months
Mean modified Rodnan skin score (mRSS) difference
Time frame: Between Month 0 and month 12
Mean modified Rodnan skin score (mRSS)
Time frame: At 3 months
Mean modified Rodnan skin score (mRSS)
Time frame: At 6 months
WHO performance status
Time frame: At month 0
WHO performance status
Time frame: At month 3
WHO performance status
Time frame: At month 6
WHO performance status
Time frame: At month 12
Scleroderma-Health Assessment Quetionnaire
Time frame: At month 0
Scleroderma-Health Assessment Quetionnaire
Time frame: At month 3
Scleroderma-Health Assessment Quetionnaire
Time frame: At month 6
Scleroderma-Health Assessment Quetionnaire
Time frame: At month 12
Short Form (36) health survey (SF36v2)
Time frame: At month 0
Short Form (36) health survey (SF36v2)
Time frame: At month 3
Short Form (36) health survey (SF36v2)
Time frame: At month 6
Short Form (36) health survey (SF36v2)
Time frame: At month 12
EQ-5D-5L quality of life questionnaire
Time frame: At month 0
EQ-5D-5L quality of life questionnaire
Time frame: At month 3
EQ-5D-5L quality of life questionnaire
Time frame: At month 6
EQ-5D-5L quality of life questionnaire
Time frame: At month 12
Forced Vital Capacity (FVC)
Time frame: At month 0
Forced Vital Capacity (FVC)
Time frame: At month 3
Forced Vital Capacity (FVC)
Time frame: At month 6
Forced Vital Capacity (FVC)
Time frame: At month 12
Diffusing capacity of Lung for carbon monoxide (DLCO)
Time frame: At month 0
Diffusing capacity of Lung for carbon monoxide (DLCO)
Time frame: At month 3
Diffusing capacity of Lung for carbon monoxide (DLCO)
Time frame: At month 6
Diffusing capacity of Lung for carbon monoxide (DLCO)
Time frame: At month 12
Response to treatment
Time frame: At month 3
Response to treatment
Time frame: At month 6
Response to treatment
Time frame: At month 12
Progression Free Survival
Time frame: At month 12
Global Rank Composite Score (GRCS)
Time frame: At month 3
Global Rank Composite Score (GRCS)
Time frame: At month 6
Global Rank Composite Score (GRCS)
Time frame: At month 12
Composite response index in dcSSc (CRISS)
Time frame: At month 3
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 9 Dec 2024.
- Individual participant dataSharing planned: Undecided
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Not yet recruitingPhase 1
Study Investigating the Safety of Anti-CD19 CAR-T Cells Therapy Produced at Gustave Roussy for Adults With Severe and Refractory Systemic Autoimmune Rheumatic Diseases
Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE)
Active, not recruitingEarly Phase 1
TBI Using IMRT and Cyclophosphamide Prior to Stem Cell Transplant for the Treatment of Severe Systemic Sclerosis
Systemic Scleroderma
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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 2 infusions of MSC and 1 infusion of MSC in people with Severe Systemic Sclerosis, run by Assistance Publique - Hôpitaux de Paris.
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 15 inclusion and 14 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: opening soon, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
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 Dominique Farge, MD PhD (0142499764 ext. +33, dominique.farge-bancel@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of treatment-related Serious Adverse Events (time frame: After each infusion). 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 9 Dec 2024.