XTMAB-16 for Sarcoidosis

Recruiting at 10 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

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Open-label Study to Evaluate the Long-term Safety and Durability of Effect of XTMAB-16 in Patients With Pulmonary Sarcoidosis With or Without Extra-pulmonary Involvement

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.

What safety data exists for XTMAB-16 in humans?

XTMAB-16 is still in clinical development and has been tested in a Phase 1 study, but specific safety data for humans is not detailed in the available research. It is a type of anti-TNF antibody, similar to other treatments that have been used for sarcoidosis, but its safety profile in humans is not fully established yet. ^{1 2 3 4 5}

What makes the drug XTMAB-16 unique for treating sarcoidosis?

XTMAB-16 is a unique treatment for sarcoidosis because it is a chimeric anti-tumor necrosis factor alpha (TNFα) antibody with a distinct molecular structure compared to other anti-TNF antibodies. It is still in clinical development and has shown promise in inhibiting granuloma formation and reducing inflammation in laboratory models. ^{1 6 7 8 9}

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

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. Switzerland 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. [2023]

2. France pubmed.ncbi.nlm.nih.gov

[Sarcoïdosis and anti-TNF: a paradoxical class effect? Analysis of the French Pharmacovigilance system database and literature review]. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: A multicenter study of 132 patients. [2018]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The CD4+ lymphopenic sarcoidosis phenotype is highly responsive to anti-tumor necrosis factor-{alpha} therapy. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Role of CD4+ T cells in sarcoidosis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes. [2019]

8. Iran pubmed.ncbi.nlm.nih.gov

The Roles of T Helper 1, T Helper 17 and Regulatory T Cells in the Pathogenesis of Sarcoidosis. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Sarcoidosis Th17 cells are ESAT-6 antigen specific but demonstrate reduced IFN-γ expression. [2021]