E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic pulmonary sarcoidosis |
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E.1.1.1 | Medical condition in easily understood language |
lung inflammatory disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037430 |
E.1.2 | Term | Pulmonary sarcoidosis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of namilumab in subjects with chronic pulmonary sarcoidosis (CPS). |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objective: To evaluate the effect of namilumab on proportion of subjects on OCS taper without rescue.
Please refer to protocol section 2.1 for other secondary objectives.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects age ≥18 years. 2. Able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form. 3. ≥6-month history of documented sarcoidosis including histological confirmation in the subject’s medical records. 4. Have HRCT and [18F]-FDG PET/CT scans at Screening consistent with active pulmonary sarcoidosis of the lung parenchyma by central read. 5. ppFVC ≥50% to ≤90% and DLCO ≥50% at Screening. 6. If receiving prednisone (or equivalent), dose must have been ≤25 mg, and dose must have been stable for at least 4 weeks prior to Screening. In addition, subject must agree to taper their steroids beginning at the time of randomization. 7. If receiving methotrexate and/or other IST, dose must have been stable for ≥3 months prior to Screening and subject must agree to cessation of their IST therapy at randomization. 8. Symptomatic as indicated by modified Medical Research Council Dyspnea scale >1 (i.e., Grade 2 or more) in the prior 6 months. 9. Female subjects must agree to use an approved highly effective birth control (BC) method (<1% failure rate per year) for at least 28 days prior to randomization, throughout the study and for 8 weeks (56 days) post last dose of study drug, unless documented to have a reproductive status of non-childbearing potential or is postmenopausal as defined below: • Non-childbearing potential defined as pre-menopausal female with medical history of total hysterectomy, bilateral oophorectomy (removal of ovaries), bilateral salpingectomy, bilateral tubal ligation, or bilateral hysteroscopic sterilization at least 3 months prior to Screening; • Postmenopausal defined as12 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 randomization and throughout the study, and for 8 weeks (56 days) following the last dose of study drug. 10.Male subjects must agree to, and attest that, female partners of childbearing potential are using one of the allowed highly effective methods of contraception as described above and for consistent duration. 11. Body Mass Index (BMI) ≤40 kg/m2 at Screening. 12. Vaccination for COVID-19 with completion of the primary series at least 2 weeks prior to randomization. |
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E.4 | Principal exclusion criteria |
1. Hospitalized for any respiratory illness ≤30 days prior to Screening. 2. ≥20% fibrosis as indicated on HRCT-scan assessed by central read prior to randomization. 3. Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD] equation) or requiring chronic renal replacement therapy. 4. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT), or alkaline phosphatase (ALP) >2 × upper limit of normal range (ULN). 5. Platelet count <100,000 per mm3. 6. Hemoglobin ≤9.5 g/dL. 7. Absolute neutrophil count <1,000 per mm3. 8. Corrected serum calcium >3.5 mmol/L (14 mg/dL). 9. Positive for anti-GM-CSF autoantibody, or history of pulmonary alveolar proteinosis (PAP). 10. Use of any biologic immunomodulator agent (approved or investigational) within the 6 months prior to Screening. Allergens for hypersensitivity desensitization or vaccines are not excluded per this criterion. Treatment with immunoglobulin within 6 months prior to Screening. Treatment with any investigational immunomodulator (e.g., Neuropilin 2 (NRP2) modulator) within 6 months prior to Screening. 11. Treatment with any Janus kinase (JAK) inhibitor within 3 months prior to Screening. 12. Participation in another interventional clinical trial within 6 months prior to Screening. 13. History of left ventricular ejection fraction (LVEF) ≤30% or New York Heart Association (NYHA) class III or IV heart failure. 14. ECG abnormalities that warrant further clinical investigation or management at Screening or Fridericia corrected QT interval (QTcF) >480 msec on the 12-lead ECG at Screening; if QTcF exceeds 480 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF measures should be used to determine eligibility. 15. Pulmonary hypertension requiring therapy. 16. Systolic blood pressure (SBP) <90 or >180 mm Hg; Diastolic blood pressure (DBP) <60 or >110 mm Hg at screening. 17. Has documented laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other approved clinical testing ≤3 months prior to randomization. 18. Administration of any fully live virus or bacterial vaccinations within 3 months prior to Screening or administration of non-live or liveattenuated vaccine within 2 weeks of randomization. Note: COVID-19 booster and influenza vaccinations are allowed to be completed during the study. 19. Systemic (oral or parenteral) antibiotic or pulse OCS treatment for any indication within 42 days prior to randomization. 20. Three or more lower, respiratory tract infections requiring antimicrobial therapy within 12 months prior to Screening. 21. History of mycetoma or fungal respiratory infection. 22. Requirement for supplemental oxygen at rest. 23. History of or planned solid organ or hematopoietic cell transplantation. 24. Prior or planned pneumonectomy and/or planned lobectomy. Note: Lobectomy performed ≥12 months prior to randomization is allowed. 25. Prior use within 12 months of Screening of, or inability to refrain from throughout the study period and 8 weeks (56 days) after last dose of study drug, smoking or using any form of inhaled tobacco, inhaled nicotine (including vaping) or inhaled cannabis preparations. 26. A diagnosis of, or presentation consistent with, Lofgren’s syndrome. 27. Other significant pulmonary disease likely to interfere with the primary endpoint; the Principal Investigator must discuss any such concerns with the Sponsor or designee prior to randomization. 28. Autoimmune disease other than sarcoidosis likely to require treatment during the subject’s participation in this study. 29. Symptoms and/or signs of extra-pulmonary sarcoidosis that are likely to warrant treatment in addition to that required for the subject’s pulmonary disease. 30. Significant ischemic heart disease, including myocardial infarction within 6 months, unstable angina, or percutaneous transluminal coronary angioplasty (PTCA)/stent within 1 month prior to Screening; or, planned coronary intervention (e.g., coronary artery bypass graft [CABG] or PTCA/stent) during the subject’s participation in this study. 31. 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. Subjects with positive serology for HIV, hepatitis B or C must have an undetectable viral load by real-time polymerase chain reaction (RT-PCR) prior to randomization. 32. Females who are pregnant or breastfeeding or intend to be during the course of the study. 33. Prior history of any malignancy (not including fully resected squamous and basal cell carcinoma of the skin, fully resected intra-epithelial neoplasia or carcinoma in situ of the cervix) or lymphoproliferative disorder within the past 5 years.
Please refer to protocol section 4.2 for detailed exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline in percent predicted forced vital capacity (ppFVC) at 26 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint: Proportion of subjects successfully achieving OCS taper without rescue
Please refer to protocol section 2.2 for other secondary endpoints.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to protocol Appendix 1 Schedule of Assessments |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Optional open-label extension (OLE) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Turkey |
United States |
Belgium |
France |
Germany |
United Kingdom |
Netherlands |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |