XTMAB-16 for Sarcoidosis

Recruiting at 33 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

Trial Summary

What is the purpose of this trial?

A phase 1b/2 study of XTMAB-16 in patients with pulmonary sarcoidosis

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 XTMAB-16 safe for humans?

The safety of XTMAB-16 in humans is still being studied, but early clinical trials have been conducted to determine safe dose levels. It is a type of anti-TNF antibody, similar to other treatments that have been used for conditions like sarcoidosis, but specific safety data for XTMAB-16 is limited. ^{1 2 3 4 5}

How is the drug XTMAB-16 different from other sarcoidosis treatments?

XTMAB-16 is unique because it is a chimeric anti-tumor necrosis factor alpha (TNFα) antibody with a distinct molecular structure, designed to inhibit granuloma formation and suppress inflammation in sarcoidosis. Unlike other treatments, it is still in clinical development and not yet approved by the FDA for any condition. ^{5 6 7 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

1. 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]

2. 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]

3. 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]

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

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

5. 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]

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

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. England pubmed.ncbi.nlm.nih.gov

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