Study of the Efficacy and Safety of a Bispecific Antibody, Teclistamab in Severe Rapidly Progressive Interstitial Lung Disease Associated With Anti-MDA5 (TEAM MDA5)

Study of the Efficacy and Safety of a Bispecific Antibody, Teclistamab in Severe Rapidly Progressive Interstitial Lung Disease Associated With Anti-MDA5.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Rapidly Progressive Interstitial Lung Disease Associated With Anti-MDA5
• Intervention / Treatment: Drug: Teclistamab(SC)

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yurdagül UZUNHAN, Pr; Phone Number: +33148955280; Email: yurdagul.uzunhan@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Dosage and subcutaneous administration of Teclistamab: Day 1: 0.06 mg/kg Day 3: 0.3 mg/kg Day 5: 1.5 mg/kg)	Drug: Teclistamab(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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	The primary endpoint is transplant-free survival at 90 days, defined as the time from inclusion to lung transplantation or death from any cause.	at 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the length of stay in hospital	Total hospital length of stay, from admission to discharge	at 90 days
To evaluate disease severity	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).	at 90 days
To evaluate the response of Interstitial Lung Disease on imaging	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	From enrollment to the end at week 24
To assess the tolerance profile of teclistamab	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 day 1 of treatment to the end of treatment (4 week )
To evaluate the response of extra-respiratory manifestations including muscular involvement	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)	From Day 0 at week 24
To evaluate overall survival	Overall Survial defined as the time from inclusion to death from any cause, with documentation of the causes of death.	from inclusion to day 90

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): October 30, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Teclistamab; severe rapidly progressive interstitial lung disease; anti-MDA5; transplant-free survival
• Other Study ID Numbers: APHP251597; 2026-526467-38-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No