TACROLIMUS for Antisynthetase syndrome-related interstitial lung disease | Interstitial lung disease

Inclusion criteria

• {"criterion_text":"- Age ≥ 18"}
• {"criterion_text":"- Signed informed consent"}
• {"criterion_text":"- Affiliation to the Social security system"}
• {"criterion_text":"- Diagnosis of ASS: positive test for any of the 5 anti-tRNA synthetase antibodies routinely tested (ELISA, Luminex or Linear-dot), including anti-Jo-1, anti-PL7, anti-PL12, anti-EJ and anti-OJ, up to 3 months prior to inclusion."}
• {"criterion_text":"- Diagnosis of ILD-related ASS: interstitial lung disease on HRCT"}
• {"criterion_text":"- Moderate to severe ILD on PFT: FVC < 80% and or cDLCO < 70%"}
• {"criterion_text":"- Beta-HCG test negative or negative uterine echography (for women of child bearing potential)"}
• {"criterion_text":"- Women of childbearing potential must have an effective contraceptive measure (hormonal, intrauterine device, intrauterine hormone-releasing system, sterilization method)) during all the duration of study treatment and 12 months after the last dose of study treatment"}
• {"criterion_text":"- Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of study treatment and 6 months after the last dose of study treatment"}

Exclusion criteria

• {"criterion_text":"- Pregnancy and/or breast feeding"}
• {"criterion_text":"- Positivity of auto-antibodies associated to Systemic Sclerosis (anti-Telomerase, anti-Centromères, anti-Polymerase III)."}
• {"criterion_text":"- Patients with QTc > 450 msec"}
• {"criterion_text":"- Patients with history of long QT syndrome (including familial) or ventricular arrhythmias"}
• {"criterion_text":"- Concomitant use of drugs prolonging QT / QTc (list of treatments in annex)"}
• {"criterion_text":"- Hypokalemia"}
• {"criterion_text":"- Patients with pulmonary hypertension detected on echocardiography during the screening/selection visit (systolic pulmonary artery pressure (PAP) was 37–50 mmHg, and/or tricuspid regurgitation velocity 2.8–3.4 ms-1) are excluded."}
• {"criterion_text":"- Others contraindications to the treatments, including hypersensitivity to the drug (including excipient and active compounds), medical contraception contraindications, severe renal failure, severe hepatic insufficiency and severe psychiatric disorders. Specific contraindications are listed for each experimental medication in Table 6 (according to updated Summary of product characteristics, see Appendix 7)"}
• {"criterion_text":"- Fever or active bacterial infection (ie. septicemia, pneumopathy, pyelonephritis, acute prostatitis …), or parasitic infection (ie. Anguillulosis …), or fungal infection (ie. Invasive pulmonary aspergillosis …), or viral infection (HIV seropositivity, Active Tuberculosis, active B/C viral hepatitis, CMV, active EBV…)"}
• {"criterion_text":"- Active neoplasm"}
• {"criterion_text":"- Previous inefficacy of Cyclophosphamide, Azathioprine or Tacrolimus, not related to adhesion problems."}
• {"criterion_text":"- Previous use of 3 daily IV steroids < 3 months, and > 10 days before patient's morphological and functional examination for enrollment (CT-scan and PFT)."}
• {"criterion_text":"- ASS-related ILD worsening or relapse while considering inclusion under Prednisone > 0.5 mg/kg/day, > 30 days prior to inclusion."}
• {"criterion_text":"- Previous use of Cyclophosphamide, Azathioprine or Tacrolimus in the last 6 months."}
• {"criterion_text":"- Severe ASS requiring ICU at the time of inclusion (respiratory disease, myocarditis), plasma exchange or IV-Ig."}

Primary endpoints

• {"endpoint_text":"- The composite primary endpoint is the time from the initiation of treatment to the first event related to ASS related ILD (progression free survival)","definition_or_measurement_approach":"Time-to-event composite endpoint: time from initiation of treatment to first ASS-related ILD event (progression-free survival)."}

Secondary endpoints

• {"endpoint_text":"- Global variation of the M0 and M12-six minute walk tests is compared (distance in meter, differential of saturation in %).","definition_or_measurement_approach":"Comparison of change from baseline (M0) to M12 in six-minute walk distance (meters) and change in oxygen saturation (%)."}
• {"endpoint_text":"- Global variation of M0 and M12-FVC and cDLCO is compared (both absolute and %)","definition_or_measurement_approach":"Comparison of change from baseline (M0) to M12 in Forced Vital Capacity (FVC) and diffusing capacity for carbon monoxide (cDLCO), both absolute values and percent predicted."}
• {"endpoint_text":"- Lung improvement is defined (in the absence of any other pulmonary disease) by 3A. Improvement of at least 20% of the dyspnea visual scale score (1-10) 3B. and/or improvement of pulmonary function tests: increase of the baseline FVC by 10% (% patient predicted value or absolute value) or of the baseline cDLCO by 15% (% patient predicted value or absolute). 3C. and/or improvement of ILD on HRCT-scan (-5% involvement of the lung parench","definition_or_measurement_approach":"Lung improvement defined by any of: ≥20% improvement in dyspnea visual scale; and/or increase in baseline FVC by ≥10% or baseline cDLCO by ≥15% (absolute or % predicted); and/or improvement on HRCT (specified thresholds for parenchymal involvement and fibrosis as assessed by independent blinded radiologist)."}
• {"endpoint_text":"- Extra-pulmonary improvement is evaluated as follow: improvement of the muscle involvement, assessed by muscle manual testing at each visit, is defined by an increased score > 20%/ biological improvement of the muscle involvement, assessed by creatine kinase levels performed at every visit, is defined by a decreased of baseline creatin kinase > 50% (IU/ml)/improvement of the joint involvement, assessed by the ACR score at every visit is defined by a decrease > 20% of baseline","definition_or_measurement_approach":"Extra-pulmonary improvement assessed by MMT (muscle manual testing) >20% increase, CK decrease >50% from baseline, and ACR joint score decrease >20% from baseline."}
• {"endpoint_text":"- Extra-pulmonary improvement (muscle and joint involvements) is evaluated as follows: 5A. improvement of the muscle involvement, assessed by MMT/150 muscle testing at baseline and M12, is defined by an increased score > 20% 5B. improvement of the joint involvement, assessed by the ACR score at each visit is define by a decrease > 20% of baseline number of swelling and painful joints.","definition_or_measurement_approach":"Evaluation at baseline and M12 using MMT-150 for muscle improvement (>20% increase) and ACR joint assessment (>20% decrease in swollen/painful joints)."}
• {"endpoint_text":"- Treatments tolerance (and efficacy) is recorded and compared as follows: any serious adverse event attributable to any experimental medication, which requires hospitalization, is recorded at any time. Side effects are declared by the patients, recorded and reported by the investigators at every visit. The number of patients switching of experimental treatment is recorded. The percentage of dose reduction of steroids and proportion of patients who require a dose increase at any time","definition_or_measurement_approach":"Safety/tolerability captured via recording SAEs requiring hospitalization, patient-reported side effects at each visit, number of patients switching experimental treatment, steroid dose reduction percentage, and proportion requiring steroid dose increases."}
• {"endpoint_text":"- The Quality of Life is assessed by the general questionnaire SF-36. Mean V1 (M0), V7 (M6) and V9 (M12) scores are compared.","definition_or_measurement_approach":"Health-related quality of life measured by SF-36 questionnaire; comparison of mean scores at baseline (V1/M0), M6 (V7), and M12 (V9)."}

France

Latest Decision Or Authorization Date

16-01-2026

Number Of Sites

16

Number Of Participants

76

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France