RESOLVE-Heart: A Study to Assess the Safety, Tolerability, and Efficacy of Namilumab in Participants With Active Cardiac Sarcoidosis
Study Details
Study Description
Brief Summary
A Randomized, Double-blind, Placebo-controlled, Study with an Open-label Cohort.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm 1 Namilumab with prednisone, or equivalent |
Drug: Namilumab
Namilumab administered subcutaneously with prednisone or equivalent
|
| Placebo Comparator: Treatment Arm 2 Placebo with prednisone, or equivalent |
Drug: Placebo
Placebo administered subcutaneously to match namilumab dosing with prednisone or equivalent
|
| Experimental: Treatment Arm 3 Namilumab with current dose of prednisone, or equivalent |
Drug: Open label Namilumab
Namilumab administered subcutaneously, with current dose of prednisone or equivalent
|
Outcome Measures
Primary Outcome Measures
- 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
- Incidence and Magnitude of Treatment-Emergent Laboratory Abnormalities [Baseline to Week 34]
- Change from Baseline in Vital Signs [Baseline to Week 34]
Measure of the change in participants in blood pressure (mm Hg)
- Change from Baseline in Vital Signs [Baseline to Week 34]
Measure of the change in participants heart rate (beats per minute)
- Change from Baseline in Electrocardiogram (ECG) Parameters [Baseline to Week 34]
Measure of heart rate (beats per minute), PR Interval (mSec), and QT Interval (mSec)
- Mean Change from Baseline in Maximum Standardized Uptake Value (SUVmax) [Baseline to Week 34]
Measurement of activity in Positron Emission Tomography (PET)
- Cumulative Arrhythmia Burden [Baseline to Week 34]
Percentage of participants with clinically significant arrhythmia
- Hospitalization for Cardiac Events [Baseline to Week 34]
Percentage of participants hospitalized for cardiac events
- Mean Change from Baseline in Echocardiogram findings [Baseline to Week 34]
Percent Left Ventricular Ejection Fraction (LVEF)
- Mean Change from Baseline in Echocardiogram findings [Baseline to Week 34]
Percent Global Longitudinal Strain
- Cumulative Oral Steroid Use and Toxicity [Baseline to Week 34]
Measure of participants oral corticosteroid use and associated toxicities
- 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 [Baseline to Week 34]
Measure of Health-Related Quality of Life
- Mean Change from Baseline in The Fatigue Assessment Scale (FAS) [Baseline to Week 34]
10 item self-reported fatigue questionnaire
- Mean Change from Baseline in Subject Global Assessment [Baseline to Week 34]
A 5-point scale assessing overall perception of frequency and severity of sarcoid symptoms
- Assessments of Population Pharmacokinetics (PPK) [Baseline to Week 34]
Trough plasma concentration
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kinevant Study Site | Gainesville | Florida | United States | 32610 |
| 2 | Kinevant Study Site | Baltimore | Maryland | United States | 21234 |
Sponsors and Collaborators
- Kinevant Sciences GmbH
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KIN-1902-2002