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NCT05890729PHASE1, PHASE2Recruiting

A Study of XTMAB-16 in Patients With Pulmonary Sarcoidosis

Xentria, Inc.

Start Date

11/10/2023

Completion Date

5/1/2029

Summary

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

Eligibility Criteria

Age Range: 18 years to 80 years

Inclusion Criteria: 1. Participant between 18 to 80 years (inclusive) of age. 2. Weighs between 45 kg and 160 kg (99 to 353 lbs) at Screening. 3. Diagnosis of pulmonary sarcoidosis (at least 6 months before Screening) using the 2020 American Thoracic Society (ATS) Clinical Practice Guideline (Crouser et al, 2020), the European Respiratory Society (ERS) or the WASOG criteria including a compatible clinical and radiologic presentation with other causes of granulomatous disease ruled out (cutaneous and ocular involvement permitted). 4. Modified Medical Research Conference (mMRC) Dyspnea Scale of ≥ 1. 5. Receiving treatment of 7.5 to 25 mg/day of oral prednisone, or equivalent, during the screening period and, at the determination of the investigator, is capable of undergoing the protocol specific corticosteroid taper regimen. 6. Receiving treatment with methotrexate, azathioprine, mycophenolate, leflunomide, chloroquine, or hydroxychloroquine for at least 3 months before Screening that has been at a stable dose for 4 weeks before Screening. All efforts should be made to maintain stable background therapy at the Screening dose through the intervention period at the Investigator's discretion. 7. PART A only: 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. 8. Polymerase chain reaction (PCR) test or rapid antigen test negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening. 9. Able to provide written informed consent. 10. In the opinion of the Investigator, the participant is capable of understanding and complying with protocol requirements Exclusion Criteria: 1. Pregnant or breastfeeding women or women who are planning to become pregnant during the study. 2. PART A ONLY: Participants \> 65 years of age. (This exclusion criterion is only applicable for EU). 3. PART A ONLY: Known potentially significant fibrotic disease and/or active inflammation contained solely in the hilar region as shown by high-resolution computed tomography (HRCT), confirmed by a central reader. Participants with current active inflammation in the hilar region with concurrent inflammation outside the hilar region may be included. A historical HRCT performed within 6 months of screening may be submitted for diagnostic confirmation by central review. If a subject's last HRCT was from \> 6 months of screening, an HRCT should be performed during screening for diagnostic confirmation by central review. 4. PART A ONLY: Any prior TNFα inhibitor therapy. 5. Clinically significant extra-pulmonary sarcoidosis requiring systemic therapy as determined by the investigator. 6. PART B ONLY: Any therapy with an anti-TNFα monoclonal antibody (e.g., infliximab, adalimumab, golimumab and their biosimilars) within 6 months. 7. Baseline percent predicted forced vital capacity (FVC) of \< 50%. 8. Prior treatment with rituximab or repository corticotropin injection within the previous 12 months. 9. Clinically significant Central Nervous System (CNS) sarcoidosis requiring therapy, except history of isolated seventh cranial nerve palsy or evidence of demyelinating neurologic disease. 10. Advanced congestive heart failure (New York Heart Association \[NYHA\] 3 or 4). 11. Current disease presentation consistent with Lofgren's syndrome (i.e., presence of the triad of erythema nodosum, bilateral hilar lymphadenopathy on chest X-ray, and joint pain). 12. Clinically significant pulmonary hypertension requiring treatment. Note: Clinically significant pulmonary hypertension requiring treatment would be defined as treatment with, i.e., prostacyclins, phosphodiesterase 5 inhibitors, and endothelin receptor antagonists. 13. Known hypersensitivity to any component of the formulation of XTMAB-16. 14. Live or messenger ribonucleic acid (mRNA) vaccination within 2 weeks before Day 1 or inoculation with a live or mRNA vaccine is planned during study participation. 15. Evidence of active or latent TB by interferon-gamma release assay (IGRA) or invasive fungal infections at Screening. 16. Known positive history of malignancy other than non-melanomatous skin cancer in the last 2 years, including in-situ carcinoma of the uterine cervix completely cured by radical surgery. 17. Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, coronavirus disease (COVID-19), TB, or a known history of human immunodeficiency virus (HIV) infection at Screening. 18. Women of childbearing potential who are sexually active with a non-sterilized male partner and are not willing to adhere to highly effective birth control measures from the time of signing the informed consent, throughout the duration of the study, and for 90 days after 5 half-lives have elapsed since the last dose of study drug. 19. Male participants who are non-sterilized and sexually active with a female partner of childbearing potential and are not willing to use highly effective contraception from the time of signing the informed consent throughout the duration of the study, and for 90 days after 5 half-lives have elapsed since last dose of study drug. 20. Clinically significant hepatic or renal disease, including uncontrolled diabetes at the discretion of the investigator. 21. Any severe prior reaction to any type of biologics or human blood product such as albumin, IgG, etc. 22. Concurrent emphysema. 23. Known hypercalcemia due to non-sarcoidosis conditions such as untreated hyperparathyroidism, at the discretion of the investigator. 24. Abnormal ECG: ventricular arrhythmias (non-sustained ventricular tachycardia (VT), multifocal or frequent premature ventricular contractions, bundle branch block, axis deviation, or abnormal Q waves). In the case of a QTcF (corrected QT interval by Fredericia) interval \> 450 ms (men) or \> 480 ms (women; participants with bundle branch block) or PR interval outside the range of 120 to 220 ms, the assessment may be repeated once for eligibility determination at Screening or Baseline. 25. Donation or loss of 450 mL or more of his or her blood volume (including plasmapheresis) or transfusion of any blood product within 90 days prior to dosing. 26. Known uncontrolled hypertension. Note: Uncontrolled hypertension is noted as blood pressure ≥ 160/100 mmHg despite antihypertensive therapy within 3 months of randomization. 27. Clinical signs and symptoms consistent with COVID-19, e.g., fever, dry cough, dyspnea, sore throat, fatigue, new smell or taste disorder or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening. 28. In the opinion of the investigator, inability to tolerate corticosteroid taper. 29. Concurrent systemic steroid use for non-sarcoidosis conditions. 30. Concurrent known auto-immune disease requiring treatment. 31. Participation in another clinical trial of an investigational agent within 3 months (small molecule) / 6 months (biologics) or 5 half-lives (if known) of the agent, whichever is longer. 32. Any condition that required hospitalization within the 3 months prior to Day 1 or is likely to require so during the study. 33. Clinically significant abnormalities in the Screening physical exam, medical history, vital signs, ECG, or clinical laboratory tests that are not known to be due to concurrent sarcoidosis, and in the opinion of the Investigator and Medical Monitor should preclude the participant's participation in the clinical study.

Interventions

DRUG

XTMAB-16 or Placebo

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Conditions

Pulmonary Sarcoidosis

Locations

Xentria Investigative Site

Birmingham, Alabama 35233

United States

Xentria Investigative Site

Denver, Colorado 80206

United States

Xentria Investigative Site

Jacksonville, Florida 32209

United States

Xentria Investigative Site

Chicago, Illinois 60611

United States

Xentria Investigative Site

Chicago, Illinois 60612

United States

Xentria Investigative Site

Iowa City, Iowa 52242

United States

Xentria Investigative Site

Baltimore, Maryland 21287

United States

Xentria Investigative Site

Detroit, Michigan 48202

United States

Xentria Investigative Site

Minneapolis, Minnesota 55455

United States

Xentria Investigative Site

Albany, New York 12208

United States

Xentria Investigative Site

New York, New York 10029

United States

Xentria Investigative Site

Greenville, North Carolina 27858

United States

Xentria Investigative Site

Cincinnati, Ohio 45267

United States

Xentria Investigative Site

Philadelphia, Pennsylvania 19140

United States

Xentria Investigative Site

Charleston, South Carolina 29425

United States

Xentria Investigative Site

Houston, Texas 77030

United States

Xentria Investigative Site

Charlottesville, Virginia 22903

United States

Xentria Investigative Site

Prague, 140 59

Czechia

Xentria Investigative Site

Aalborg, 9000

Denmark

Xentria Investigative Site

Aarhus, 8200

Denmark

Xentria Investigative Site

Odense, 5000

Denmark

Xentria Investigative Site

Roskilde, 4000

Denmark

Xentria Investigative Site

Vejle, 7100

Denmark

Xentria Investigative Site

Bielsk Podlaski, 15-044

Poland

Xentria Investigative Site

Lodz, 90-153

Poland

Xentria Investigative Site

Barcelona, 08035

Spain

Xentria Investigative Site

Barcelona, 08036

Spain

Xentria Investigative Site

Seville, 41013

Spain

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, England CV22DX

United Kingdom

University College London Hospitals NHS Foundation Trust

London, England NW12PG

United Kingdom

King's College Hospital NHS Foundation Trust

London, England SE59RS

United Kingdom

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, England NR47UY

United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, England OX37LE

United Kingdom

NHS Tayside

Perth, Scotland PH11NX

United Kingdom