Efficacy and Safety of Subcutaneous Belimumab in Adults with Connective Tissue Disease-Associated Interstitial Lung Disease

3 1 1

What is this study about?

This clinical trial is focused on studying a group of lung conditions known as Interstitial Lung Disease (ILD), which are associated with Connective Tissue Disease (CTD). These diseases can cause scarring of the lungs, leading to breathing difficulties. The study will evaluate the effectiveness and safety of a medication called Belimumab, which is given as an injection under the skin. Belimumab is being tested to see if it can help reduce the decline in lung function in people with ILD related to CTD.

The trial will compare the effects of Belimumab to a placebo, in addition to the standard treatments that participants are already receiving for their condition. Participants will receive either Belimumab or a placebo through injections over a period of 52 weeks. The main goal is to see if Belimumab can help maintain lung volume better than the placebo. Throughout the study, participants will be monitored for changes in their lung function and overall health.

Participants in the study will be adults who have been diagnosed with ILD associated with CTD, such as Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), or other similar conditions. The study aims to provide more information on whether Belimumab can be a beneficial addition to the current treatment options for these lung diseases. The trial will also track any side effects or health changes experienced by participants during the study period.

1 study treatment begins

After joining the study, you start treatment with belimumab or placebo. Belimumab is given as a 200 mg injection under the skin, also called subcutaneous use. The placebo is a sterile solution given as a subcutaneous injection in a pre-filled syringe and contains no active medicine.

You receive the study treatment together with standard therapy. The study compares belimumab with placebo in addition to this standard treatment.

2 regular treatment period

During the trial, you continue to receive the assigned injection at the dose of 200 mg by subcutaneous injection. The study is double-blind, which means that the treatment assignment is hidden from you and the study team.

The treatment period lasts until Week 52. The study checks whether the treatment helps reduce the decline in lung volume in people with interstitial lung disease, which means scarring or inflammation in the lungs.

3 study assessments during the trial

During the study, your lung function is measured. The main measurement is FVC, which means forced vital capacity. This is the amount of air you can breathe out after taking a deep breath.

Your results are compared with your starting values at Week 52. The study also checks changes in other lung and health measures, including FVC % predicted, DLco % predicted (a test of how well oxygen moves from your lungs into your blood), and several symptom and quality-of-life scores.

The study also checks whether your disease gets worse, whether death occurs, and whether you have changes in steroid dose, fatigue, breathing symptoms, and overall well-being.

4 safety monitoring

Throughout the trial, you are monitored for adverse events, which means unwanted medical problems, serious adverse events, which are more severe problems, and adverse events of special interest, which are specific problems the study is watching for.

The study also checks for respiratory-related hospitalisations, which means hospital stays because of breathing or lung problems, up to Week 52.

Who Can Join the Study?

Age 18 years or older at the time of signing the informed consent form.
A documented diagnosis of one of the following connective tissue diseases, confirmed by accepted medical criteria: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), idiopathic inflammatory myopathy (IIM) including polymyositis, dermatomyositis, or antisynthetase syndrome, Sjogren’s syndrome (primary Sjogren’s syndrome, also called pSS), or mixed connective tissue disease (MCTD).
Patients with an overlap syndrome may join if their main diagnosis is RA, SLE, IIM, pSS, or MCTD. An overlap syndrome means a person has features of more than one autoimmune disease.
A diagnosis of interstitial lung disease (ILD) shown on high-resolution CT (HRCT), which is a detailed lung scan, with disease affecting at least 10% of the whole lung.
Evidence that the lung disease is still active or getting worse, shown by at least one of these: a 10% or greater relative decline in FVC within the past 24 months, or a smaller decline in FVC together with worsening breathing symptoms or worsening scan findings, or a 10% or greater relative decline in DLCO within the past 24 months together with worsening scan findings, or worsening breathing symptoms together with worsening scan findings, or a decline in both FVC and DLCO within the allowed ranges, or signs of active inflammatory ILD on the screening scan, or a recent IIM-related ILD diagnosis within 12 months with a decline in FVC or only a very small improvement.
FVC means forced vital capacity, which is the amount of air a person can blow out after taking a deep breath. DLCO means a test that measures how well the lungs move oxygen into the blood.
Currently receiving stable standard therapy for ILD and/or the underlying connective tissue disease, or having previously failed standard therapy, or not being able to tolerate it.
If using oral corticosteroids such as prednisolone, the dose must be 20 mg/day or less and stable for at least 30 days before Day 1. Corticosteroids are medicines that reduce inflammation.
If using mycophenolate mofetil (MMF), the dose must be 3000 mg/day or less and stable for at least 90 days before Day 1.
If using mycophenolate sodium, the dose must be 2160 mg/day or less and stable for at least 90 days before Day 1.
If using methotrexate (MTX), the dose must be 25 mg/week or less and stable for at least 90 days before Day 1.
If using azathioprine (AZA), the dose must be 2.5 mg/kg/day or less and stable for at least 90 days before Day 1.
If using tacrolimus, the dose must be 2.5 mg daily or less, or up to 5 mg daily if that is the locally approved or recommended dose, and stable for at least 90 days before Day 1.
If using cyclosporin, the dose must be 4 mg/kg/day or less and stable for at least 90 days before Day 1.
If using hydroxychloroquine, the dose must be 400 mg/day or less and stable for at least 90 days before Day 1.
If using leflunomide, the dose must be 20 mg/day or less and stable for at least 90 days before Day 1.
Must be able and willing to self-administer the study medicine, or have a caregiver who is able and willing to give the study medicine throughout the study. Self-administer means giving the medicine to oneself.
If female, must not be pregnant or breastfeeding.
If female and able to become pregnant, must use a highly effective contraceptive method with less than 1% failure rate during the study and for at least 4 months after the last dose. Contraception means a method used to prevent pregnancy.
If female and able to become pregnant, must have a negative highly sensitive pregnancy test within 24 hours before the first dose. A pregnancy test may be done with urine or blood, depending on local rules.
Must be capable of giving signed informed consent, meaning the person understands the study and agrees to take part and follow the study rules.

Who Cannot Join the Study?

The person does not have connective tissue disease–related interstitial lung disease (CTD-ILD), or has another type of interstitial lung disease instead.
There is significant emphysema on lung scans, meaning the air sacs in the lungs are damaged enough that emphysema is worse than the interstitial lung disease.
There is confirmed progressive multifocal leukoencephalopathy (PML), a serious brain infection, or new or worsening nervous system problems that cannot be explained.
There is a serious allergy to human or mouse proteins, to humanized monoclonal antibodies (lab-made antibody medicines), or to contrast agents used for some scans.
There are multiple or severe drug allergies, inability to tolerate topical corticosteroids (steroid creams or ointments), or severe allergic skin reactions after treatment, such as erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis.
The person has a high depression score with a serious risk of suicide, any suicidal behavior in the last 6 months, suicidal thoughts in the last 2 months, or the investigator believes there is a significant suicide risk.
The person has had lymphoma, leukemia, or any other cancer within the past 5 years, except certain skin cancers that were fully removed and have not spread for 3 years.
The person had breast cancer within the past 10 years.
The person had major surgery, including joint surgery, within 3 months before screening, or major surgery is planned during the study.
The person has an active infection, or certain recent or unresolved infections, including opportunistic infections (infections that happen more easily when the immune system is weak), serious infections needing IV antibiotics or hospital care within the last 60 days, infections needing oral antibiotics or antiviral medicine within the last 30 days, any active bacterial, viral, or fungal infection on the first day of treatment, or osteomyelitis (bone infection) that is not fully resolved.
The person had shingles with symptoms within 3 months before the first dose.
The person has systemic sclerosis as the main diagnosis.
The person has active tuberculosis (TB) or untreated latent TB infection (TB infection without symptoms), unless treatment has already been completed or has been underway long enough as allowed by the study rules.
The person has had a previous or planned major organ transplant, such as heart, lung, kidney, or liver transplant, or a bone marrow transplant.
The person had plasmapheresis (a blood cleaning procedure), extracorporeal photopheresis (a treatment that changes blood cells outside the body), or use of plasma filtering devices within 6 months before the first dose.
The person has ever received anti-BLyS medicines, including belimumab.
The person recently received certain biologic medicines or monoclonal antibodies that affect the immune system, within the study’s required waiting period.
The person received rituximab or another B-cell depleting therapy (medicine that lowers certain immune cells) within 6 months before the first dose.
The person recently received JAK inhibitors (immune system medicines), other non-biologic systemic immunosuppressive medicines, or other targeted synthetic disease-modifying medicines within the study’s required waiting period.
The person received cyclophosphamide within 6 months before the first dose.
The person used anti-fibrotic medicines (medicines that slow scarring), tyrosine kinase inhibitors, or PDE4B inhibitors within 4 weeks before the first dose.
The person received cytotoxic drugs (drugs that kill cells, often used in cancer treatment), such as chlorambucil or nitrogen mustard, within 6 months before the first dose.
The lung disease is rapidly getting worse, shown by a drop of 10% or more in FVC (forced vital capacity, the amount of air a person can forcefully breathe out) between screening and baseline, and/or a recent hospital stay for lung problems.
The person received intramuscular or intravenous corticosteroids (steroids given by injection or vein) within 4 weeks before the first dose.
The person had a live or live-attenuated vaccine (a vaccine with a weakened germ) within 30 days before the first dose, or plans to get one during the study.
The person is expected not to follow the study rules about medicines and vaccines during the study or the 8-week safety follow-up period.
The person is currently in, or recently took part in, another research study with an investigational treatment, or in another medical research study within the required time before randomization.
The person has a positive HIV antibody test.
The person has signs of hepatitis B infection that do not meet the study’s allowed exceptions, such as a positive HBsAg test or detectable HBV DNA when further testing is required.
The person has a positive hepatitis C antibody test at screening or within 3 months before treatment, unless the antibody test is positive because of a past infection that has fully cleared and a confirmatory hepatitis C RNA test is negative.
The person has a positive hepatitis C RNA test at screening or within 3 months before the first dose.
The person has a history of primary immunodeficiency (an inherited weak immune system), hypogammaglobulinemia (too little IgG, an important infection-fighting antibody), or IgA deficiency (too little IgA, another antibody).
The person has grade 3 or worse neutropenia, meaning a very low number of neutrophils, which are white blood cells that help fight infection.
The breathing test results are too low: FVC is 45% or less of the expected value, or DLco (a test of how well oxygen moves from the lungs into the blood) is 40% or less of the expected value.
There is another important abnormal lab result that the investigator thinks could change how the study drug is absorbed, broken down, or removed from the body, create a safety risk, or make the results hard to interpret.
The person has had too much ionizing radiation exposure above normal background levels in the past 3 years, from work or previous research studies.
The person currently abuses drugs or alcohol, or has done so within 1 year before the first dose.
The person has a sensitivity to any study treatment or ingredient, or another allergy that the investigator believes makes study participation unsafe.
The person uses medicines for medical conditions that are not approved by the health authority in their country or region.
ALT is more than 2 times the upper limit of normal, meaning a liver blood test is too high.
Total bilirubin is more than 1.5 times the upper limit of normal, unless the increase is isolated and the direct bilirubin is less than 35%.
The person has cirrhosis (permanent scarring of the liver) or unstable liver or bile duct disease, such as fluid in the abdomen, brain effects from liver disease, blood clotting problems, low blood protein, enlarged veins in the food pipe or stomach, or ongoing yellowing of the skin or eyes.
The heart rhythm test shows QTc above 450 milliseconds, or above 480 milliseconds if the person has a bundle branch block (a problem with the heart’s electrical wiring).
There is a history of or current diffuse alveolar hemorrhage (bleeding into the air sacs of the lungs) or another lung condition, sign, or symptom that could confuse the study results.
The person has pulmonary arterial hypertension that requires treatment, meaning high blood pressure in the lung arteries.
The person depends on continuous oxygen support.
The person has a heart, lung, liver, kidney, stomach, hormone, blood, or nerve disorder that could strongly affect how the study drug works, create risk, or make the results hard to understand.
The person has obstructive lung disease, shown by a pre-bronchodilator FEV1/FVC ratio below 0.7. This means airflow is blocked in the lungs before using a breathing medicine.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Center For Pediatric And Adolescent Medicine Of The Johannes Gutenberg University Mainz	Mainz	Germany
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Centre Hospitalier Universitaire De Lille	Lille	France
University Hospital Maastricht	Maastricht	The Netherlands
Oncopole Claudius Regaud	Toulouse	France
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Azienda Ospedaliera Universitaria Universita’ Degli Studi Della Campania Luigi Vanvitelli	Naples	Italy
Hospital Universitario De Navarra	Pamplona	Spain

Other Sites

Site Name	City	Country
Azienda Ospedaliera di Padova	Padua	Italy
Evangelismos S.A.	Athens	Greece
Centre Hospitalier Universitaire Rouen	Rouen	France
General University Hospital Of Larissa	Larissa	Greece
Virgen del Rocío University Hospital	Sevilla	Spain
Ospedale San Raffaele S.r.l.	Milan	Italy
Fondazione IRCCS Policlinico San Matteo	Pavia	Italy
Universitair Medisch Centrum Utrecht	Utrecht	The Netherlands
Universita’ Campus Bio-medico Di Roma	Rome	Italy
Universita’ Degli Studi Di Verona	Verona	Italy
St.-Josef-Stift	Sendenhorst	Germany
Universita’ Politecnica Delle Marche	Ancona	Italy
Staedtisches Klinikum Dresden	Dresden	Germany
Azienda Ospedaliero Universitaria Di Modena	Modena	Italy
Centre hospitalier universitaire de Liege	Liege	Belgium
Ruhrlandklinik Westdeutsches Lungenzentrum Am Universitaetsklinikum Essen gGmbH	Essen	Germany
Azienda Sanitaria Universitaria Friuli Centrale	Udine	Italy
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Hopital Beaujon	Clichy	France
Vrije Universiteit Brussel	Jette	Belgium
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo	Italy
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur	Namur	Belgium
Johannes Wesling Klinikum Minden	Minden	Germany
Asst Centro Specialistico Ortopedico Traumatologico Gaetano Pini Cto	Milan	Italy
University General Hospital Attikon General Hospital Of West Attica H Agia Varvara	Chaidari	Greece
Azienda Ospedaliero Universitaria Pisana	Pisa	Italy
Cuzlgnfmi Utcqhxviooijgx Sittjnjrh	Woluwe-Saint-Lambert	Belgium
Hyyzqhma Vwnf dxbvkqoh	Barcelona	Spain
Edadxeo Urefkkbqzijf Mmlwglo Cfgzhos Rxpsmbbhn (uovjifr Mam	Rotterdam	The Netherlands
Uxjxshvwfmoqolkbsppyz Wnyvyhnzj Akq	Wuerzburg	Germany
Hsexejff Dy Lk Szfdy Chse I Sgig Ped	Barcelona	Spain
Hwfxljjl Uaigdeignyoqa Mjwbacj Dk Vzeskqkfzj	Santander	Spain
Cbcejo Hljiowrosia Rmtarzqg Dzwthfrsvgenos	Angers	France
Fuhbzhili Pkgn Ly Imeulfurknkic Bvyizcjme Doe Hyzvuikk Ulpkujcxtmnss Ll Pyp	Madrid	Spain

Trial status

Country	Status	Recruitment Start
Belgium	Recruiting	31.10.2024
France	Recruiting	31.10.2024
Germany	Recruiting	31.10.2024
Greece	Recruiting	31.10.2024
Italy	Recruiting	31.10.2024
Spain	Recruiting	31.10.2024
The Netherlands	Not yet recruiting	31.10.2024

Trial locations

Investigated drugs:

Belimumab

Benlysta is a medicine that contains belimumab. It is given as an injection under the skin. In this study, it is being tested to see if it can help slow down the loss of lung volume in adults who have interstitial lung disease linked to connective tissue disease, when used together with standard treatment.

Investigated diseases:

Interstitial lung disease

Interstitial Lung Disease – Interstitial lung disease is a group of disorders that cause inflammation and scarring in the tissue around the air sacs of the lungs. Over time, the lung tissue becomes stiffer, which makes it harder for the lungs to expand and move oxygen into the blood. The condition often progresses gradually, with worsening shortness of breath and reduced lung function. In connective tissue disease-associated interstitial lung disease, this lung damage develops in relation to an immune system disorder that also affects other parts of the body.

Trial ID:

2024-513018-36-00

Protocol code:

221672

Trial Phase:

Therapeutic confirmatory (Phase III)

Other Trials to Consider

#1 Clinical Trials Search in Europe

Efficacy and Safety of Subcutaneous Belimumab in Adults with Connective Tissue Disease-Associated Interstitial Lung Disease

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?