Effects of Telitacicept vs Cyclophosphamide on Lupus Related Interstitial Lung Disease

Official title

A Randomized, Positvel Controlled, Multicenter Study of Effects of Telitacicept vs Cyclophosphamide on Lupus Realted Interstitial Lung Disease

Overview

Recent data indicate that Telitacicept is beneficial for lupus nephritis. Our goal is to determine whether Telitacicept is an effective and safe treatment, compared to standard-of-care Cyclophosphamide, for subclinical and clinical ILD in patients with early lupus.

Detailed description

Pulmonary abnormalities are present in up to 60% of patients with SLE, and up to 10% of the patients will develop clinical interstitial lung disease (ILD). Recent data indicate that Telitacicept is beneficial for lupus nephritis. Our goal is to determine whether Telitacicept is an effective and safe treatment, compared to standard-of-care Cyclophosphamide, for subclinical and clinical ILD in patients with early lupus. The study also explores disease mechanisms in lungs and serum immunological interaction, to identify potential biomarkers for diagnosis, prognosis, and response to treatment of lupus-ILD.

Interventions

• Drug Methylprednisolone (Corticosteroid)
  In addition to conventional treatment (methyl-40mg or less /d), the treatment group also received hydroxychloroquine (100mg-200mg each time twice a day), and thalidomide (50mg-100mg each time once a day) could be added as appropriate.
• Drug Immunosuppressant other than CYC
  The control group only received conventional treatment (methyl 40 mg/d or less), and other traditional immunosuppressants (including but not limited to cyclophosphamide, tacrolimus, sirolimus, cyclosporine, leflunomide, azathioprine, motecophenol ester, hydroxychloroquine, tripterine, methotrexate and sulazazopyridine, etc.). No more than 3 types of immunosuppressant should be added during the whole treatment period, and the dose should not exceed 30% from the baseline period)
• Drug Telitacicept Freeze-dried powder Injection 80mg
  Telitacicept is a TACI-Fc fusion protein, a type of drug used to treat autoimmune diseases. It works by targeting two key proteins, BLyS and APRIL, which are involved in the development and function of B cells, a type of white blood cell. By blocking these proteins, telitacicept can help to reduce B cell activity and suppress the immune system's overactivity in autoimmune diseases. Subcutaneous injection dose ranges from 80mg once a week to 160mg once a week.
• Drug Cyclophosphamide (CYC)
  Cyclophosphamide iv injection is used for severe complications of systemic lupus erythematosus 400mg twice a week

Primary outcome measures

• Correlation between change from baseline at week 52 in forced vital capacity (FVC) [percentage (%) predicted] [Time frame: At baseline and at week 24, 52]

Secondary outcome measures (6)

• Correlation between change from baseline at week 52 in diffusing capacity for carbon monoxide (DLco) [percentage (%) predicted] [Time frame: At baseline and at week 24, 52]
• Anti-double-stranded DNA antibody conversion ratio [Time frame: At baseline and at week 12, 24, and 52]
• Complement C3 and C4 levels return to normal ratios [Time frame: At baseline and at week 12, 24, and 52]
• Six minutes walking distance [Time frame: At baseline and at week 12, 24, and 52]
• Changes from baseline in cumulative corticosteroid dose at week 52 [Time frame: At baseline and at week 52]
• Krebs von den Lungen-6 [Time frame: At baseline and at week 12, 24, and 52]

Eligibility criteria

Inclusion criteria

• Meet the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus;
• Male or non-pregnant female aged ≥ 18 years;
• Diagnosis by high-resolution lung CT (HRCT) is clearly consistent with interstitial lung disease (ILD);
• FEV1/FVC%≥60% and diffusion function DLCO (measured value/estimated value) ≥40%;
• Patients voluntarily participate in this trial, have good compliance, and have the ability to understand and sign informed consent before the study.

Exclusion criteria

• Alanine aminotransferase and/or aspartate aminotransferase (ALT/AST) > 5 times the upper limit of normal;
• severe chronic kidney disease (stage IV) or need for dialysis (estimated glomerular filtration rate (eGFR) < 30ml/min/1.73m2);
• Hemoglobin < 80 g/L;
• WBC < 2.0×10\^9;
• Platelet < 50×10\^9;
• Is pregnant or breastfeeding;
• Expected transfer to another hospital in a non-study site within 4 weeks (possibility of loss to follow-up);
• Life expectancy does not exceed 24 weeks;
• Have a history of severe allergies;
• Patients with other serious lung diseases or other clinically significant serious abnormalities in the lungs;
• Are using antitumor drugs, other immunosuppressants or immunomodulatory therapies;
• Significant pulmonary hypertension;
• Previous clinical or echocardiographic evidence of significant right heart failure;

• Right heart catheterization showing cardiac index ≤ 2 L/min/m2;
• Pulmonary hypertension requiring treatment with epoprostenol/traprostacyclin.
• Patients with severe cardiovascular disease:

• myocardial infarction within 6 months;
• Unstable angina within 6 months.
• Risk of bleeding, any of the criteria listed below:

• known genetic predisposition to bleeding;
• Patients who require the following treatments:

i. Fibrinolytic therapy, full-dose therapeutic anticoagulation (e.g., vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin); ii. High-dose antiplatelet therapy. \[Note: Prophylactic low-dose heparin or heparin flush solution (e.g., enoxaparin, 4000 I.U. S.C. per day) required for maintenance of indwelling intravenous access devices is not prohibited.) and prophylactic antiplatelet therapy (e.g., acetylsalicylic acid up to 325 mg/day, or clopidogrel at a dose of 75 mg/day, or other antiplatelet therapy at the same dose).

• History of hemorrhagic central nervous system (CNS) events within 12 months;
• Any of the following conditions within a period of 3 months:

• hemoptysis or hematuria;
• Active gastrointestinal bleeding or gastrointestinal ulcers;
• Have previously undergone hematopoietic stem cell transplantation (HSCT), or plan to receive HSCT in the following year, or plan to undergo major surgery.
• Women who are pregnant, breastfeeding or planning to become pregnant during the test;
• 28 days before administration or 3 months after administration, women of childbearing age are unwilling or unable to use highly effective contraceptive methods;
• According to the investigator's point of view, the patient has alcohol or drug abuse;
• History of dysphagia or any gastrointestinal disease that affects drug
• Patients with contraindications to the use of tatacept;
• Subjects deemed unsuitable for participation in the study by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT07077486 · Tongji Hospital

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗