A Study to Assess the Safety, Tolerability, and Efficacy of Namilumab in Participants With Active Cardiac Sarcoidosis

Study Overview
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Brief Summary
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A Randomized, Double-blind, Placebo-controlled, Study with an Open-label Cohort.

Detailed Description
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A Randomized, Double-blind, Placebo-controlled, Study with an Open-label Cohort. Participants enrolled in Cohort A will be randomized to receive namilumab, or placebo, and will also be treated with a daily dose of prednisone or equivalent, in addition to any other background Immunosuppressive therapy (IST) currently prescribed. Namilumab or placebo will be administered subcutaneously (SC) every 4 weeks through Week 30 after the initial dosing period. Participants enrolled in Cohort B will be administered namilumab SC in an open-label fashion, and must continue their background therapy without change to any ongoing oral corticosteroid dose or ISTs. Further details are in the protocol.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase 2a Study With an Open-label Cohort to Assess the Safety, Tolerability, and Efficacy of Namilumab in Subjects With Active Cardiac Sarcoidosis

Conditions
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Sarcoidosis, Cardiac

Intervention / Treatment
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* Drug: Namilumab
* Drug: Placebo
* Drug: Open label Namilumab
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age ≥18 years Able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form History of documented sarcoidosis (must include histological confirmation, from any organ, in the subject's medical history or records) Meet Heart Rhythm Society Cardiac Sarcoid Diagnostic Criteria (modified) Female subjects must agree to use an approved highly effective birth control (BC) method Male subjects must agree to, and attest that, female partners of childbearing potential are using one of the allowed highly effective methods of contraception Body Mass Index (BMI) <40 kg/m2 at Screening. Vaccination for COVID-19 with completion of the primary series at least 2 weeks prior to randomization Exclusion Criteria: Hospitalized for any respiratory or cardiac illness ≤30 days prior to Screening Known pulmonary hypertension requiring therapy Autoimmune disease other than sarcoidosis likely to require treatment during the subject's participation in this study Symptoms and/or signs of extracardiac sarcoidosis that are likely to warrant treatment in addition to that required for the subject's cardiac disease Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD] equation) or requiring renal replacement therapy Hemoglobin ≤9.5 g/dL Participation in another interventional clinical trial within 6 months prior to Screening and throughout the duration of participation in this study Systolic blood pressure (SBP) <90 or >180 mm Hg; Diastolic blood pressure (DBP) <60 or >110 mm Hg at Screening Has documented laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other approved clinical testing ≤3 months prior to randomization Significant valvular heart disease known or anticipated to require surgical repair or replacement during the subjects' participation in this study Female subjects who are pregnant or breastfeeding or intend to be, during the study History of severe allergic or anaphylactic reactions to therapeutic proteins or known sensitivity to namilumab or to its inactive components Any other acute or chronic medical condition, that in the judgment of the Investigator or Sponsor, may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results, and would make the participant inappropriate for entry into this study Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm 1<br>Namilumab with prednisone, or equivalent | Drug: Namilumab<br>* Namilumab administered subcutaneously<br>Drug: Prednisone<br>* Prednisone or equivalent<br>|
| Placebo Comparator: Treatment Arm 2<br>Placebo with prednisone, or equivalent | Drug: Placebo<br>* Placebo administered subcutaneously to match namilumab dosing<br>Drug: Prednisone<br>* Prednisone or equivalent<br>|
| Experimental: Treatment Arm 3<br>Namilumab with current dose of prednisone, or equivalent | Drug: Open label Namilumab<br>* Namilumab administered subcutaneously<br>Drug: Prednisone<br>* Prednisone or equivalent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation |  | Baseline to Week 34 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Magnitude of Treatment-Emergent Laboratory Abnormalities |  | Baseline to Week 34 | 
| Change from Baseline in Vital Signs | Measure of the change in participants in blood pressure (mm Hg) | Baseline to Week 34 | 
| Change from Baseline in Vital Signs | Measure of the change in participants heart rate (beats per minute) | Baseline to Week 34 | 
| Change from Baseline in Electrocardiogram (ECG) Parameters | Measure of heart rate (beats per minute), PR Interval (mSec), and QT Interval (mSec) | Baseline to Week 34 | 
| Mean Change from Baseline in Maximum Standardized Uptake Value (SUVmax) | Measurement of activity in Positron Emission Tomography (PET) | Baseline to Week 34 | 
| Cumulative Arrhythmia Burden | Percentage of participants with clinically significant arrhythmia | Baseline to Week 34 | 
| Hospitalization for Cardiac Events | Percentage of participants hospitalized for cardiac events | Baseline to Week 34 | 
| Mean Change from Baseline in Echocardiogram findings | Percent Left Ventricular Ejection Fraction (LVEF) | Baseline to Week 34 | 
| Mean Change from Baseline in Echocardiogram findings | Percent Global Longitudinal Strain | Baseline to Week 34 | 
| Cumulative Oral Steroid Use and Toxicity | Measure of participants oral corticosteroid use and associated toxicities | Baseline to Week 34 | 
| Mean Change from Baseline in Glycosylated Hemoglobin |  | Baseline to Week 34 | 
| Proportion of subjects requiring rescue therapy (either cohort) and proportion of subjects successfully achieving steroid taper without requiring rescue therapy (Cohort A) |  | Baseline to Week 34 | 
| Mean Change from Baseline in Multi-Organ Health Status Questionnaire | Measure of Health-Related Quality of Life | Baseline to Week 34 | 
| Mean Change from Baseline in The Fatigue Assessment Scale (FAS) | 10 item self-reported fatigue questionnaire | Baseline to Week 34 | 
| Mean Change from Baseline in Subject Global Assessment | A 5-point scale assessing overall perception of frequency and severity of sarcoid symptoms | Baseline to Week 34 | 
| Assessments of Population Pharmacokinetics (PPK) | Trough plasma concentration | Baseline to Week 34 |