Severe Rapidly Progressive Interstitial Lung Disease Associated With Anti-MDA5
Conditions
Keywords
severe rapidly progressive interstitial lung disease, anti-MDA5, Teclistamab, transplant-free survival
Brief summary
Patients with severe, rapidly progressive diffuse interstitial lung disease (RP ILD) with anti-MDA5 have an appalling prognosis and the lack of effective medical treatment leads to lung transplantation being proposed as salvage treatment. Currently, transplant-free survival at 90 days (D90) is approximately 25%, dropping to less to 10% among those requiring mechanical ventilation. Peripheral lymphopenia and elevated anti-MDA5 antibody levels are associated with greater disease severity, highlighting the involvement of mature T and B lymphocytes in disease pathogenesis. Teclistamab, a bispecific antibody targeting the B-cell maturation antigen (BCMA) on plasma cells and engaging T cells - approved for the treatment of refractory multiple myeloma - has recently shown rapid and promising effects in patients with autoimmune conditions, including one MDA5-positive patient, while maintaining a favourable safety profile. We hypothesize that this bispecific antibody could represent a promising and safe therapeutic option for patients with severe MDA5-associated RP-ILD.
Interventions
DRUGTeclistamab(SC)
Dosage and subcutaneous administration of Teclistamab: Day 1: 0.06 mg/kg Day 3: 0.3 mg/kg Day 5: 1.5 mg/kg)
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Drug
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient ≥ 18 years old * MDA5 antibody positivity * ILD confirmed by chest HRCT * Within less than 3 months after disease onset * Refractory after more than 7 days to high dose steroids and two immunosuppressants drugs as first-line treatment. * Confirmation of refractoriness by the national emergency multidisciplinary discussion (MDD), * Worsening of respiratory symptoms with respiratory distress defined by increase in oxygen supply to reach SpO2\>95% or requirement of mechanical ventilation * Written informed consent obtained from the patient or the trusted support person designated in advance by the patient * Patients covered by the French social security system * Effective contraception for woman of childbearing age during treatment and for five months after the last dose of teclistamab. * Effective contraception for men, having a partner of childbearing age, during treatment and for three months after the last dose of teclistamab.
Exclusion criteria
* Patient with known hypersensitivity to teclistamab, substance active or excipients, including sodium or polysorbate * Patient or the trusted person designed by the patient not able to give their consent * Known diagnosis of a serious comorbidity: active cancer, malignant blood disease, ongoing infection, stroke or seizure within 6 months * Patient who received a live vaccine within 4 weeks prior to study inclusion. * Patient under judicial protection, deprivation of liberty * Patient participating in another clinical trial with an investigational medicinal product * Pregnant or breastfeeding woman * Patient on AME (state medical aid)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary objective is to demonstrate the efficacy of teclistamab in improving transplant-free survival of patients with anti-Melanoma differentiation-associated protein 5 associated rapidly progressive diffuse interstitial lung disease. | at 90 days | The primary endpoint is transplant-free survival at 90 days, defined as the time from inclusion to lung transplantation or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the length of stay in hospital | at 90 days | Total hospital length of stay, from admission to discharge |
| To evaluate disease severity | at 90 days | Disease severity evaluated using the World Health Organization Clinical Progression Scale adapted for Interstitial Lung Disease-associated respiratory failure (11-point ordinal scale from 0 to 10). |
| To evaluate the response of Interstitial Lung Disease on imaging | From enrollment to the end at week 24 | Interstitial Lung Disease response will be based on evolution of Interstitial Lung Disease extent on centralized chest Computed Tomography at Day 0, Week 2, Week 4, Week 12 and Week 24 |
| To assess the tolerance profile of teclistamab | to day 1 of treatment to the end of treatment (4 week ) | Tolerance assessed by the occurrence and gradation of adverse events, including infections complications detected by microbiological monitoring protocolised in ICU units during the follow-up period. |
| To evaluate the response of extra-respiratory manifestations including muscular involvement | From Day 0 at week 24 | Dermatomyositis disease monitoring assessed at Day 0, Week 2, Week 4, Week 12 and Week 24 through: Manual Muscle Testing 8 score (set of 8 designated muscles tested unilaterally) |
| To evaluate overall survival | from inclusion to day 90 | Overall Survial defined as the time from inclusion to death from any cause, with documentation of the causes of death. |
Contacts
CONTACTYurdagül UZUNHAN, Pr
Outcome results
None listed