ANCA-Associated Vasculitis (AAV), Childhood-onset Systemic Lupus Erythematous, Juvenile Dermatomyositis, Juvenile Myasthenia Gravis
Conditions
Brief summary
Safety, tolerability and efficacy of Descarte-08 in children, adolescents and young adults with childhood-onset systemic lupus erythematosus, ANCA-associated vasculitis, juvenile myasthenia gravis, and juvenile dermatomyositis
Interventions
DRUGDescartes-08
In part 1, three different doses will be administered to 3 participants with either disease indication to establish maximum tolerated dose In part 2, the MTD established in Part-1 will be administered as six once-weekly infusions to up to 10 participants per each of four baskets (cSLE, AAV, JDM and JMG) in an outpatient setting.
Sponsors
Cartesian Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1: establish Maximum tolerated dose Part 2: MTD to be given once weekly for 6 weeks
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least age 12 * definitive diagnosis of childhood-onset systemic lupus erythematous, juvenile Myasthenie gravis, juvenile dermatomyositis and AAV * Signs and symptoms of moderate disease * History of systemic treatment * Parent/Guardian/Patient must be able to give written informed consent
Exclusion criteria
* Major chronic illness that is not well managed at the time of study entry and in the opinion of the investigator may increase the risk to the patient; * Abnormal PT/INR or PTT increased \> 1.5-fold or patient is on anticoagulation therapy (except in cases of elevated PTT with documented lupus anticoagulant; or in patients who have been on stable doses of anticoagulation therapy for more than 6 months of VTE diagnosis; or in patients on stable doses of anticoagulation therapy for at least 8 weeks of atrial fibrillation diagnosis; these conditions will not be exclusionary unless, in the investigator's opinion, they make participation in the study unsafe); * ANC \< 1000 cells/microliter ; * Hemoglobin \< 8.0 g/dL ; * Platelets \< 50,000/mm3 (NOTE: platelet transfusions are permissible); * ALT and/or AST with GGT ≥ 3× upper limit of normal * Creatine Clearance less than 30mL/min /1.73 m2; * History of primary immunodeficiency, organ, or allogeneic bone marrow transplant; * Patients must be seronegative for hepatitis B surface antigen; * Patients must be seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patients must be tested for the presence of viremia by RT-PCR and must be HCV RNA negative; * History of positive HIV or positive HIV at screening; * Active tuberculosis or positive QuantiFERON test at screening; * Any other laboratory abnormality that, in the opinion of the investigator, may jeopardize the subject's ability to participate in the study; 23. Any active significant cardiac or pulmonary disease not related to the primary indication as determined by principal investigator and medical monitor Note: Patients with asthma and COPD controlled with inhaled medications are allowed; 24. Any arterial or venous thromboembolic events in the past 3 months; 25. History of malignancy that required treatment in the past 3 years except for successfully-treated squamous cell and/or basal cell carcinoma of the skin and/or breast or colon cancer that is surgically removed and did not require adjuvant chemotherapy or radiotherapy; 26. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer); 27. Receipt of a live vaccination within 4 weeks prior to baseline (Day 1) or intent to receive live vaccination during the study (Note: mRNA-based vaccines such as those against SARS-CoV-2 are not considered live; likewise, the Janssen Covid-19 vaccine is not live); 28. History of significant recurrent infections or any active infection that may interfere with the patient's participation in the opinion of the investigator; 29. Any known psychiatric illness that may interfere with the patient's participation in the study in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose in Part 1, type and frequency of treatment related SAE's in Part 2 | Days 22 and 50 for Part1 , Days 22, 50 and Months 3,6,9 and 12 for part 2 | The primary endpoint for Part-1 is the Maximum Tolerated Dose (MTD), defined as the Dose Level at which no more than 20% of the patients treated have shown Dose-Limiting Toxicity (DLT), i.e. at which 3 patients received all 6 weekly infusions without a DLT by Day 50; or 6 patients received 3 weekly infusions with no more than 1 patient having a DLT by Day 50. The primary endpoint for Part-2 is the type and frequency of treatment-related SAEs. This will be assessed on Days 22, 50 and Months 3,6,9,12 |
| Maximum Dose Tolerated | Days 2250 for Part 1, Days 11,50, month 3 for part 2 in addition to months, 4,6,9,12 | The primary endpoint for Part-1 is the Maximum Tolerated Dose (MTD), defined as the Dose Level at which no more than 20% of the patients treated have shown Dose-Limiting Toxicity (DLT), i.e. at which 3 patients received all 6 weekly infusions without a DLT by Day 50; or 6 patients received 3 weekly infusions with no more than 1 patient having a DLT by Day 50. The primary endpoint for Part-2 is the type and frequency of treatment-related SAEs. |
Countries
United States
Contacts
CONTACTCartesian Clinical Trials
Outcome results
None listed