PRA023 for Systemic Sclerosis-Associated ILD

(ATHENA-SSc-ILD Trial)

Not currently recruiting at 183 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Must be taking: Nintedanib, MMF, Methotrexate, Azathioprine

Disqualifiers: Pulmonary hypertension, Infections, Smoking, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 50 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tulisokibart (also known as PRA023) to determine its safety and effectiveness for individuals with a lung condition linked to systemic sclerosis, a disease affecting the skin and organs. Participants will receive either the experimental treatment or a placebo (a substance with no active medicine) through an IV infusion. The trial seeks individuals who have had systemic sclerosis for five years or less, exhibit skin thickening, and have lung issues confirmed by a specific type of scan. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that if you are on certain medications like nintedanib, mycophenolate mofetil, methotrexate, azathioprine, or corticosteroids, you must be on a stable dose. This suggests you may continue these medications if they are stable.

Is there any evidence suggesting that PRA023 is likely to be safe for humans?

Research has shown that tulisokibart, also known as PRA023, has been tested for safety in people with a lung condition linked to systemic sclerosis (SSc-ILD). In these studies, most participants handled the treatment well, with serious side effects being rare. Some experienced mild issues like headaches or nausea, but these were not severe. This suggests the treatment is fairly safe. However, as this research remains in the early stages, more information is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for systemic sclerosis-associated ILD?

Unlike the standard treatments for systemic sclerosis-associated interstitial lung disease (SSc-ILD), which often focus on reducing inflammation and slowing disease progression, PRA023 is unique because it targets a specific immune pathway linked to fibrosis. This is an exciting development because PRA023 works by inhibiting TL1A, a molecule involved in the fibrotic process of the disease. Researchers are optimistic about PRA023 because this targeted approach could more effectively address the underlying cause of lung damage in SSc-ILD, potentially improving outcomes for patients who have limited treatment options.

What evidence suggests that PRA023 might be an effective treatment for SSc-ILD?

In this trial, participants will receive either tulisokibart, also known as PRA023, or a placebo. Earlier studies have shown tulisokibart's promise in treating interstitial lung disease (SSc-ILD) linked to systemic sclerosis. Research suggests that this treatment might improve lung function in people with this condition. Specifically, patients taking tulisokibart demonstrated better lung capacity compared to those on a placebo, indicating potential to slow lung damage caused by SSc-ILD. While more research is needed, these early results offer hope for those affected by this challenging disease. ^{1 2 3 4 6}

Who Is on the Research Team?

Prometheus Biosciences

Principal Investigator

Clinical Trials Call Center

Are You a Good Fit for This Trial?

This trial is for people with systemic sclerosis that started within the last 5 years and associated lung disease, who are not current smokers. They must have a certain level of lung function and be on stable medication doses. Participants need to use effective contraception and cannot join if they have other inflammatory diseases, serious recent infections, or significant heart or lung complications.

Inclusion Criteria

I was diagnosed with systemic sclerosis less than 5 years ago.

Diffusing capacity of lung for carbon monoxide (DLCO)≥ 45% of predicted normal

FVC ≥ 45% of predicted normal

Exclusion Criteria

Is a current smoker or smoking within 6 months of screening

Meets the protocol criteria for important laboratory exclusion criteria

I do not have any current infections, serious infections in the past 3 months, or chronic bacterial infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tulisokibart or placebo via IV infusion

50 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PRA023

Trial Overview The study tests PRA023's safety and effectiveness in treating systemic sclerosis-related lung disease compared to a placebo. A companion diagnostic tool is also used. The goal is to see if PRA023 can help manage this condition better than existing treatments.

How Is the Trial Designed?

Group I: Tulisokibart Experimental Treatment 2 Interventions

Tulisokibart IV administered by IV infusion

Group II: Placebo Placebo Group 2 Interventions

Placebo administered by IV infusion

Who Is Running the Clinical Trial?

Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Lead Sponsor

Trials

6

Recruited

600+

Prometheus Biosciences, Inc.

Lead Sponsor

Trials

6

Recruited

600+

Published Research Related to This Trial

Biologic therapies targeting immune system components, such as cytokines and immune cells, show promise as alternative treatments for systemic sclerosis (SSc), a complex autoimmune disorder characterized by collagen deposition and microvascular changes.

Preliminary data suggest that these targeted immunotherapies may be effective and safe in treating SSc, based on results from both animal studies and human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted immunotherapies in systemic sclerosis. Avouac, J., Allanore, Y.[2017]

In a study involving 20 Japanese patients with systemic sclerosis, tocilizumab showed a trend towards improved lung function compared to placebo, with a mean change in forced vital capacity of 3.3% for tocilizumab versus -3.8% for placebo during the double-blind period.

The safety profile of tocilizumab was favorable, with lower rates of serious adverse events compared to placebo, particularly in the open-label extension phase where no serious events were reported for continuous tocilizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tocilizumab in Japanese patients with systemic sclerosis and associated interstitial lung disease: A subgroup analysis of a global, randomised, controlled Phase 3 trial. Kuwana, M., Takehara, K., Tanaka, Y., et al.[2023]

In a study using SKG mice, which develop rheumatoid arthritis and lung disease, treatment with nintedanib significantly reduced lung collagen levels and improved lung function after 6 weeks, indicating its potential efficacy in treating RA-associated interstitial lung disease.

Nintedanib also showed early intervention benefits by significantly reducing the development of arthritis, suggesting it may be a promising therapeutic option for patients suffering from both rheumatoid arthritis and lung fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nintedanib reduces pulmonary fibrosis in a model of rheumatoid arthritis-associated interstitial lung disease. Redente, EF., Aguilar, MA., Black, BP., et al.[2022]

In a phase 3 trial involving 210 participants, tocilizumab did not significantly improve skin fibrosis compared to placebo, as indicated by the modified Rodnan skin score (mRSS) change after 48 weeks.

However, tocilizumab showed a positive effect on lung function, with a significant improvement in forced vital capacity (FVC%) compared to placebo, suggesting it may help preserve lung function in early systemic sclerosis-associated interstitial lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Khanna, D., Lin, CJF., Furst, DE., et al.[2021]

In a phase II study involving 97 patients with diffuse cutaneous systemic sclerosis (dcSSc), romilkimab significantly improved skin scores compared to placebo, with a mean difference of -2.31 in the modified Rodnan skin score after 24 weeks.

The safety profile of romilkimab was comparable to placebo, with most adverse events being mild to moderate, and no significant cardiac safety concerns were observed, suggesting it may be a safe option for treating early dcSSc.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, placebo-controlled, 24-week, phase II, proof-of-concept study of romilkimab (SAR156597) in early diffuse cutaneous systemic sclerosis. Allanore, Y., Wung, P., Soubrane, C., et al.[2021]

Systemic sclerosis is a severe rheumatic disease with high mortality, primarily due to fibrotic changes affecting skin and internal organs, particularly leading to life-threatening conditions like interstitial lung disease and pulmonary arterial hypertension.

Recent advancements in understanding the disease's heterogeneity have led to the approval of targeted therapies, such as tocilizumab and nintedanib, which help slow lung function decline in patients with systemic sclerosis-associated interstitial lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Approaches to Systemic Sclerosis: Recent Approvals and Future Candidate Therapies. Lescoat, A., Roofeh, D., Kuwana, M., et al.[2023]

A 69-year-old man with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) showed significant improvement in symptoms and lung function after switching to upadacitinib, a Janus kinase inhibitor, after failing multiple other treatments.

This case suggests that JAK inhibitors may be a promising option for patients with refractory RA-ILD, highlighting the need for further research into their efficacy in this specific condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of a Patient with Drug-Refractory Rheumatoid Arthritis-Associated Interstitial Lung Disease with Upadacitinib: A Case Report. Nishii, Y., Okamoto, M., Zaizen, Y., et al.[2023]

Biologic therapies like rituximab have shown significant improvements in lung function and skin disease in patients with systemic sclerosis, suggesting they may be effective treatment options despite the lack of universally accepted therapies.

While tocilizumab and abatacept have shown some potential benefits, their results have not consistently reached statistical significance, indicating that more research is needed to establish their efficacy in treating systemic sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is biological therapy in systemic sclerosis the answer? Misra, DP., Ahmed, S., Agarwal, V.[2021]

In a real-life study involving 93 patients with systemic sclerosis (SSc) treated with tocilizumab and 3180 patients receiving standard care, tocilizumab showed trends favoring improvements in skin and lung fibrosis, although these were not statistically significant.

The safety profile of tocilizumab was consistent with previous reports, suggesting it is a relatively safe option for SSc patients, and the results indicate potential effectiveness that warrants further investigation in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort. Kuster, S., Jordan, S., Elhai, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05270668

Phase 2 Safety and Efficacy Study of Tulisokibart (MK-7240 ... A Double Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-7240/PRA023 in Subjects With Systemic Sclerosis Associated ...

2. trials.arthritis.org trials.arthritis.org/trials/NCT05270668

Phase 2 Safety and Efficacy Study of Tulisokibart (MK-7240 ... Phase 2 Safety and Efficacy Study of Tulisokibart (MK-7240/PRA023) in Subjects With Systemic Sclerosis Associated With Interstitial Lung Disease (SSc-ILD) (MK- ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20540044

Clinical Trials The purpose of this study is to assess the safety and efficacy of tulisokibart in participants with SSc-ILD. Participation eligibility.

4. clinicaltrial.be clinicaltrial.be/en/details/31691?per_page=20&only_recruiting=0&only_eligible=0

Phase 2 Safety and Efficacy Study of Tulisokibart (MK-724... Has systemic sclerosis related interstitial lung disease confirmed by HRCT; FVC ≥ 45% of predicted normal; Diffusing capacity of lung for carbon ...

5. bu.trialstoday.org bu.trialstoday.org/trial/NCT05270668

Phase 2 Safety and Efficacy Study of Tulisokibart (MK-7240 ... The purpose of this study is to assess the safety and efficacy of tulisokibart in participants with SSc-ILD. Conditions. Diffuse Cutaneous ...

6. hss.edu hss.edu/research/clinical-trials/pra023-ssc-ild

A Double Blind, Randomized, Placebo-Controlled Study to ... This is a study to investigate the treatment of Interstitial Lung Disease (ILD) with PRA023. The trial consists of weekly infusions of PRA023/placebo every 4 ...