Namilumab in Subjects with Chronic Pulmonary Sarcoidosis

Overview

About this study

The purpose of this study is to evaluate the effectiveness of namilumab in subjects with chronic pulmonary sarcoidosis (CPS).

Sarcoidosis is a multi-organ autoimmune disease characterized by non-necrotizing granulomas believed to be formed from an exaggerated immune response to unidentified antigens. 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male or female age ≥ 18 years.
  • Is able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form.
  • Have a ≥ 6-month history of documented sarcoidosis including histological confirmation in the subject’s medical records.
  • Have high-resolution computed tomography (HRCT) and PET scan consistent with active pulmonary sarcoidosis of the lung parenchyma confirmed by central read.
  • Have FVCp ≥ 50% to ≤ 90% and DLCO ≥ 50%.
  • If receiving prednisone (or equivalent), dose must have been ≤25 mg, and dose must have been stable for at least 4 weeks prior to randomization.
  • Symptomatic as indicated by mMRC Dyspnea scale >1 (i.e., Grade 2 or more) in the prior year.
  • If receiving methotrexate and/or other immunosuppressive therapy (IST) dose must have been stable for ≥ 3 months prior to randomization.
  • Female subjects must agree to use an approved highly effective birth control (BC) method (< 1% failure rate per year) throughout the study, unless documented to have a reproductive status of non-childbearing potential or is postmenopausal:
    • Non-childbearing potential defined as pre-menopausal female with medical history of bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries), or hysterectomy; hysteroscopic sterilization;
    • Postmenopausal defined as 12 months of spontaneous amenorrhea; otherwise, a follicle stimulating hormone (FSH) confirmation will be required. For females with questionable menopausal history (e.g., irregular menstrual periods and age > 40 years) a documented serum FSH level must be ≥ 30 mIU/mL;
    • Woman of childbearing potential (WCBP) who is already using an established method of highly effective contraception or agrees to use one of the allowed BC methods, for at least 28 days prior to the start of dosing, throughout the study, and for 4 months following the last dose of study drug.
  • Males who are sexually active must agree to use one of the allowed BC methods. Male subjects must also agree to sufficiently minimize the risk of pregnancy throughout study participation (and for 4 months following the last dose of study drug).
  • Body Mass Index (BMI) 18 to 40 kg/m^2 at screening.
  • Subjects must agree to steroid taper, and cessation of their IST therapy at randomization.
  • Completion of vaccination for COVID-19 at least 2 weeks prior to randomization.

Exlusion Criteria:

  • Hospitalized for any respiratory illness ≤ 30 days prior to screening.
  • Prednisone dose > 25 mg/day at any time in the previous 4 weeks.
  • ≥ 20% fibrosis as indicated on CT-scan that has been confirmed by central read prior to randomization.
  • eGFR ≤30 mL/min/1.73 m^2 (MDRD equation) or requiring hemofiltration or dialysis.
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 3 × upper limit of normal range (ULN).
  • Platelet count <100,000 per mm^3.
  • Hemoglobin ≤ 9.5 g/dL.
  • Absolute neutrophil count < 1,000 per mm^3.
  • History of known anti-GM-CSF autoAb or tests positive at screening, or history of pulmonary alveolar proteinosis (PAP).
  • Use of biologic — approved or investigational agents (e.g., anti-TNFα, anti-IL-1, anti-IL-6, anti-IL-17, anti-IL-12/23 or specific anti-IL-23 inhibitors, anti CD20, anti-IL-18) within the 6 months prior to screening.
  • Prior use of immunoglobulin within 6 months prior to screening.
  • Prior use of any investigational immunomodulator (e.g., NRP2 modulator) within 6 months of screening.
  • Prior use of any JAK inhibitor within 3 months of screening.
  • Participation in another interventional clinical trial within 6 months prior to screening.
  • Known left ventricular ejection fraction (LVEF) ≤30% or NYHA class III or IV heart failure.
  • ECG abnormalities that warrant further investigation, in the opinion of the Investigator.
  • Pulmonary hypertension requiring therapy.
  • Systolic blood pressure (SBP)  < 90 or > 180 mm Hg; Diastolic blood pressure (DBP) < 60 or > 110 mm Hg.
  • Known COVID-19 infection within 3 months prior to screening.
  • Have received any live virus or bacterial vaccinations < 3 months of screening. Age-appropriate non-live vaccinations may be administered during screening so long as the last vaccine dose is administered at least 2 weeks prior to planned randomization.
  • Any infection requiring antibiotics or pulse of OCS where completion of treatment has been < 30 days prior to screening.
  • History of 3 or more lower respiratory tract infections requiring anti-microbial therapy in the past year.
  • Any history of mycetoma or fungal respiratory infection.
  • Requirement for supplemental oxygen at rest.
  • Prior history of, or likely to have any organ transplantation during study including OLE.
  • History of smoking (or vaping) in the prior year or current use. Occasional use (defined as less frequently than once per month) is allowable, though subjects should be counseled to remain abstinent during the study including OLE.
  • Other significant pulmonary disease likely to interfere with the primary endpoint, in the opinion of the Investigator.
  • Other autoimmune disease likely to require therapy during the study.
  • Symptoms and features of extra-PS that may warrant treatment in addition to that required for lung involvement.
  • Significant ischemic heart disease (i.e., myocardial infarction within 6 months, unstable angina or PCTA/stent within 1 month or planned intervention during study).
  • Known or suspected active and untreated/inadequately treated tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B or C infection. Subjects with latent TB may be enrolled if anti-TB therapy is commenced prior to randomization.
  • For women: pregnant or planning to become pregnant during the study or currently breastfeeding.
  • Prior history of any malignancy or lymphoproliferative disorder (not including fully resected basal cell carcinoma of the skin, fully resected intra-epithelial neoplasia or carcinoma in situ) within the past 5 years.

Eligibility last updated 12/23/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Eva Carmona Porquera, M.D., Ph.D.

Open for enrollment

Contact information:

Michael Stachowitz

(507) 284-4862

Stachowitz.Michael@mayo.edu

More information

Publications

Publications are currently not available