XTMAB-16 for Sarcoidosis

Recruiting at 31 trial locations

Overseen By Xentria, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Xentria, Inc.

Must be taking: Prednisone, Methotrexate, Azathioprine, others

Must not be taking: TNFα inhibitors, Rituximab

Disqualifiers: Pregnancy, CNS sarcoidosis, Congestive heart failure, others

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

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?

This trial tests a new treatment called XTMAB-16 for individuals with pulmonary sarcoidosis, a condition that causes lung inflammation. Researchers aim to determine if XTMAB-16 can reduce symptoms compared to a placebo. Participants will receive varying doses of the treatment or a placebo to identify the most effective and safe dosage. Those diagnosed with pulmonary sarcoidosis for at least six months and currently taking specific medications like prednisone might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you continue taking your current medications like prednisone, methotrexate, azathioprine, mycophenolate, leflunomide, chloroquine, or hydroxychloroquine at a stable dose. You should not stop these medications unless advised by the study investigator.

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

Research has shown that XTMAB-16 has been tested for safety in people with pulmonary sarcoidosis. In one study, 39 patients received different doses of XTMAB-16. This study was carefully controlled, with some participants receiving the actual treatment and others a placebo (a harmless, inactive substance). The aim was to assess treatment tolerance.

Another study examined how XTMAB-16 works in a lab model of sarcoidosis. While this does not directly prove safety in humans, it helps clarify the treatment's effects.

Overall, these studies suggest that researchers are working to determine the safest doses of XTMAB-16. However, XTMAB-16 is not yet approved for any condition, so ongoing research will further clarify its safety. ^{1 2 3 4 5}

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

Most treatments for sarcoidosis, like corticosteroids or immunosuppressants, aim to reduce inflammation but can have significant side effects. XTMAB-16 is unique because it targets specific pathways involved in the disease, potentially offering a more precise approach to treatment. Researchers are excited about XTMAB-16 because it might provide a more targeted therapy with fewer side effects compared to the broader action of current options. Additionally, the varied dosing schedules being tested could offer flexibility in treatment plans, tailoring the approach to individual patient needs.

What evidence suggests that this trial's treatments could be effective for pulmonary sarcoidosis?

Research has shown that XTMAB-16, which participants in this trial may receive, may help treat pulmonary sarcoidosis. Early studies found that this treatment can lower the activity of an inflammation process related to the disease, with stronger effects observed at higher doses. XTMAB-16 also proved effective in lab tests that imitate sarcoidosis, suggesting it might work in people. Although the treatment remains under study, these early results are promising for its potential to manage pulmonary sarcoidosis. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

Adults aged 18-80 with pulmonary sarcoidosis, able to follow the study plan, weighing 45-160 kg, and on stable doses of certain medications can join. They must not have been hospitalized recently or be likely to need hospitalization during the trial. Participants should not have other significant health issues like uncontrolled diabetes or hypertension, recent malignancies (except some skin cancers), severe reactions to biologics, active infections including COVID-19 and TB, or require certain treatments for sarcoidosis.

Inclusion Criteria

I am taking a low to moderate dose of prednisone or similar medication, and can follow a specific plan to reduce it.

Willing to refrain from consumption of grapefruit or grapefruit juice [pomelos, exotic citrus fruits, or grapefruit hybrids] from screening visit until after the final dose

You tested negative for COVID-19 using a PCR or rapid antigen test before the screening.

Exclusion Criteria

I have had cancer other than non-melanoma skin cancer or cervical carcinoma in-situ in the last 2 years.

I haven't donated or lost significant blood, or received a transfusion in the last 3 months.

I have not taken rituximab or repository corticotropin in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive XTMAB-16 at varying doses or placebo every 2 or 4 weeks for 12 weeks

12 weeks

Treatment Part B

Participants receive XTMAB-16 at the established dose or placebo for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XTMAB-16

Trial Overview The trial is testing XTMAB-16 against a placebo in patients with pulmonary sarcoidosis. It's an early-stage study (phase 1b/2) designed to evaluate how safe XTMAB-16 is and how well it works compared to a non-active treatment.

How Is the Trial Designed?

Group I: Part B - XTMAB-16 (dose established in Part A) for 24 weeks or Placebo Experimental Treatment 1 Intervention

Group II: Part A - XTMAB-16: 4 mg/kg every 4 weeks (Q4W) for 12 weeks or Placebo Experimental Treatment 1 Intervention

Group III: Part A - XTMAB-16: 4 mg/kg every 2 weeks (Q2W) for 12 weeks or Placebo Experimental Treatment 1 Intervention

Group IV: Part A - XTMAB-16: 2 mg/kg every 4 weeks (Q4W) for 12 weeks or Placebo Experimental Treatment 1 Intervention

Group V: Part A - XTMAB-16: 2 mg/kg every 2 weeks (Q2W) for 12 weeks or Placebo Experimental Treatment 1 Intervention

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

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]

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]

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]

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 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]

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]

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. 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.

3. 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.

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 ...