XTMAB-16 for Sarcoidosis

Enrolling by invitation at 11 trial locations

Overseen By Xentria, Inc Xentria, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Xentria, Inc.

Must be taking: Steroids

Disqualifiers: Treatment-related AEs, Treatment failure

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called XTMAB-16 for individuals with pulmonary sarcoidosis, a condition causing inflammation in the lungs and sometimes other parts of the body. The goal is to assess the treatment's long-term safety and effectiveness. Participants who have completed an earlier study with XTMAB-16 and are maintaining a stable dose of steroids are needed. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable steroid dose for at least 2 weeks before starting, so you may need to continue your current steroid medication.

Is there any evidence suggesting that XTMAB-16 is likely to be safe for humans?

Research has shown that XTMAB-16 may help treat pulmonary sarcoidosis, a condition where clusters of inflammatory cells form in the lungs. In a study with 39 patients, researchers tested different doses of XTMAB-16 and found it reduced activity in a specific inflammatory pathway related to the disease. This suggests the treatment might help manage symptoms.

Another study examined the safety of XTMAB-16 and patient tolerance. Researchers assessed patient reactions to the treatment and any side effects. Although the treatment is not yet approved for any condition, the research is promising enough to warrant further trials.

Since this is a Phase 2 trial, the treatment has already undergone safety testing in smaller groups. This phase focuses on its safety over a longer period and at different doses. If considering participation, it's important to understand that all treatments have potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sarcoidosis?

Unlike the standard treatments for sarcoidosis, which often include corticosteroids and immunosuppressants, XTMAB-16 is unique because it targets specific immune system pathways with a monoclonal antibody. This treatment offers a more targeted approach, potentially reducing inflammation with fewer side effects than traditional therapies. Researchers are excited about XTMAB-16 because it could provide a more precise and effective treatment option, improving patient outcomes and quality of life.

What evidence suggests that XTMAB-16 might be an effective treatment for sarcoidosis?

Research has shown that XTMAB-16, the treatment under study in this trial, may help treat pulmonary sarcoidosis. Early studies found that XTMAB-16 lowered the activity of a specific inflammation process linked to sarcoidosis, with higher doses proving more effective. Additionally, in lab tests that mimic the disease, XTMAB-16 effectively targeted sarcoidosis granulomas, which are clumps of inflammatory cells. Although XTMAB-16 is not yet approved, these initial results suggest it might help manage the inflammation seen in sarcoidosis. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for patients with pulmonary sarcoidosis who completed the XTMAB-16-201 study. They should have finished either Week 12 or Week 24 assessments and must be on a stable steroid dose for at least two weeks before starting this extension study.

Inclusion Criteria

I completed Week 12 or 24 assessments in the XTMAB-16-201 study.

I have been on a stable steroid dose for at least 2 weeks before joining this part of the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XTMAB-16 treatment to evaluate long-term safety and durability of effect

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Long-term evaluation of safety and durability of effect of XTMAB-16

What Are the Treatments Tested in This Trial?

Interventions

• XTMAB-16

Trial Overview

The trial is testing the long-term safety and effectiveness of a drug called XTMAB-16 in treating pulmonary sarcoidosis, which may also affect other parts of the body. It's an open-label extension, meaning everyone knows they're getting XTMAB-16.

How Is the Trial Designed?

Group I: XTMAB-16 Treatment Experimental Treatment 1 Intervention

Dose to be established in the XTMAB-16-201 Study.

XTMAB-16 is already approved in United States, European Union for the following indications:

Approved in United States as XTMAB-16 for:

• Pulmonary sarcoidosis (Orphan Drug Designation)

Approved in European Union as XTMAB-16 for:

• Pulmonary sarcoidosis (Orphan Drug Designation)

Who Is Running the Clinical Trial?

Xentria, Inc.

Lead Sponsor

Trials

7

Recruited

1,000+

Published Research Related to This Trial

In patients with active sarcoidosis, there is an increased ratio of Th17 to Treg cells in the blood and bronchoalveolar lavage fluid, suggesting a significant role of Th17 cells in the disease's progression.

The study highlights the potential for anti-IL-17 therapies to be an effective treatment option for sarcoidosis, as Th17 cells and their associated cytokines like IL-17A are implicated in the formation and maintenance of granulomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Roles of T Helper 1, T Helper 17 and Regulatory T Cells in the Pathogenesis of Sarcoidosis. Mortaz, E., Rezayat, F., Amani, D., et al.[2022]

Patients with sarcoidosis have higher levels of Th-17 cells in their blood and bronchoalveolar lavage fluid, which are specific to mycobacterial antigens, indicating a targeted immune response.

Despite the presence of these Th-17 cells, they produce less IFN-γ compared to healthy individuals, suggesting a potential reduction in immune function that may play a role in the development of sarcoidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sarcoidosis Th17 cells are ESAT-6 antigen specific but demonstrate reduced IFN-γ expression. Richmond, BW., Ploetze, K., Isom, J., et al.[2021]

A total of 46 cases of sarcoidosis were identified during anti-TNF treatment, with 7 cases reported in the French Pharmacovigilance system and 39 cases from international literature, indicating a potential class-effect of anti-TNF therapies.

Sarcoidosis primarily occurred in patients with rheumatoid arthritis and spondylarthropathy, and its development during anti-TNF therapy suggests a paradoxical reaction, although the exact mechanism behind this phenomenon remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sarcoïdosis and anti-TNF: a paradoxical class effect? Analysis of the French Pharmacovigilance system database and literature review]. Javot, L., Tala, S., Scala-Bertola, J., et al.[2019]

Activated CD4(+) T lymphocytes, particularly the TCR AV2S3(+) subset, play a crucial role in the inflammatory process of sarcoidosis, with their increased levels in patients suggesting a potential target for immunotherapy.

Dysfunctional regulatory T cells may contribute to granuloma formation in sarcoidosis, indicating that understanding these T-cell subpopulations could lead to new treatment strategies for managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of CD4+ T cells in sarcoidosis. Grunewald, J., Eklund, A.[2021]

In a study involving 232 patients, infliximab (IFX) showed potential effectiveness for treating certain manifestations of sarcoidosis, particularly lung disease, while etanercept (ETN) did not improve ocular symptoms.

Despite some positive responses, the overall evidence for the efficacy of TNF antagonists in sarcoidosis is insufficient, and there were notable safety concerns, including a mean rate of serious adverse events of 39.9 per 100 patient-years, necessitating careful evaluation of risks before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of TNF antagonists in sarcoidosis: data from the Spanish registry of biologics BIOBADASER and a systematic review. Maneiro, JR., Salgado, E., Gomez-Reino, JJ., et al.[2022]

In patients with pulmonary sarcoidosis, higher proportions of Th17.1 cells were found in the mediastinal lymph nodes (MLNs) compared to healthy controls, indicating their potential role in the disease's pathology.

The presence of Th17.1 cells in bronchoalveolar lavage fluid (BALF) was significantly higher in patients who developed chronic sarcoidosis, suggesting that these cells could serve as both a diagnostic and prognostic marker for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes. Broos, CE., Koth, LL., van Nimwegen, M., et al.[2019]

XTMAB-16, a chimeric anti-TNFα antibody, has shown promising activity in an in vitro model of sarcoidosis granuloma formation, inhibiting granuloma development and interleukin-1β secretion with effective concentrations (IC50) of 5.2 and 3.5 μg/mL, respectively.

The study supports a dosing regimen of 2 or 4 mg/kg of XTMAB-16 administered every 2 or 4 weeks, with predicted lung concentrations expected to exceed the effective levels observed in vitro, guiding its continued clinical development for treating pulmonary sarcoidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leveraging in vitro and pharmacokinetic models to support bench to bedside investigation of XTMAB-16 as a novel pulmonary sarcoidosis treatment. Offman, E., Singh, N., Julian, MW., et al.[2023]

In a study of 132 patients with severe and refractory sarcoidosis, TNF antagonists showed a clinical response rate of 64%, particularly effective for symptoms involving the nervous system, heart, skin, and upper respiratory tract.

While TNF antagonists helped reduce the need for prednisone, they were associated with a high rate of adverse events (52%), including infections and allergic reactions, leading to treatment interruptions in 23% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: A multicenter study of 132 patients. Jamilloux, Y., Cohen-Aubart, F., Chapelon-Abric, C., et al.[2018]

A specific phenotype of sarcoidosis characterized by CD4(+) lymphopenia has been identified, which shows resistance to conventional treatments like corticosteroids and methotrexate.

In a study of five patients treated with infliximab, an anti-TNF-alpha antibody, all patients showed significant increases in CD4(+) T-cell counts and improvement in clinical symptoms, indicating that this treatment may be particularly effective for this sarcoidosis phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The CD4+ lymphopenic sarcoidosis phenotype is highly responsive to anti-tumor necrosis factor-{alpha} therapy. Crouser, ED., Lozanski, G., Fox, CC., et al.[2018]

Citations

1.

atsjournals.org

atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A3547

XTMAB16 Study: A Phase 2, Randomized, Double-blind ...

Preclinical data for XTMAB-16 demonstrated reduced activation of an inflammatory pathway implicated in pulmonary sarcoidosis in a dose-dependent manner (Offman ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37021060/

Leveraging in vitro and pharmacokinetic models to support ...

The current study demonstrates the activity of XTMAB-16 in a well-established in vitro sarcoidosis granuloma model, although XTMAB-16 is not yet approved.

3.

xentria.com

xentria.com/news/22

Xentria Advances XTMAB16 Study in Pulmonary ...

XTMAB16 Study is a randomized, double-blind, placebo-controlled, Phase 1a/2b trial that enrolled 39 patients in dose-ranging study.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05890729

A Study of XTMAB-16 in Patients With Pulmonary Sarcoidosis

A Seamless, Phase 1b/2 Multiple Ascending Dose/Proof of Concept Study of XTMAB-16 in Patients With Pulmonary Sarcoidosis With or Without Extrapulmonary ...

5.

clinicaltrials.eu

clinicaltrials.eu/inn/xtmab-16/

Xtmab-16 – Application in Therapy and Current Clinical ...

This clinical trial is focused on studying the long-term effects of a treatment called XTMAB-16 for patients with pulmonary sarcoidosis. Pulmonary sarcoidosis ...