A Study to Assess the Safety, Tolerability, and Efficacy of Namilumab in Participants With Active Cardiac Sarcoidosis (RESOLVE-Heart)

• ClinicalTrials.gov Identifier: NCT05351554
• Recruitment Status: Terminated
• First Posted: April 28, 2022
• Last Update Posted: March 31, 2023
• Sponsor: Kinevant Sciences GmbH
• Information provided by (Responsible Party): Kinevant Sciences GmbH

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Sarcoidosis, Cardiac	Drug: Namilumab; Drug: Placebo; Drug: Open label Namilumab	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 23, 2022
• Actual Primary Completion Date: November 15, 2022
• Actual Study Completion Date: December 13, 2022

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 :

1. Incidence and Severity of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation [ Time Frame: Baseline to Week 34 ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

United States, California

Kinevant Study Site

Palo Alto, California, United States, 94304

United States, Colorado

Kinevant Study Site

Denver, Colorado, United States, 80206

United States, Connecticut

Kinevant Study Site

New Haven, Connecticut, United States, 06519

United States, Florida

Kinevant Study Site

Gainesville, Florida, United States, 32610

United States, Iowa

Kinevant Study Site

Iowa City, Iowa, United States, 52242

United States, Maryland

Kinevant Study Site

Baltimore, Maryland, United States, 21234

United States, Massachusetts

Kinevant Study Site

Boston, Massachusetts, United States, 02115

United States, Michigan

Kinevant Study Site

Ann Arbor, Michigan, United States, 48109

United States, New York

Kinevant Study Site

New York, New York, United States, 10029

United States, Ohio

Kinevant Study Site

Cleveland, Ohio, United States, 44195

United States, Oregon

Kinevant Study Site

Portland, Oregon, United States, 97239

United States, South Carolina

Kinevant Study Site

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Kinevant Sciences GmbH

Investigators

• Study Director: Hayes Dansky, MD; Kinevant Sciences

More Information

• Responsible Party: Kinevant Sciences GmbH
• ClinicalTrials.gov Identifier: NCT05351554
• Other Study ID Numbers: KIN-1902-2002
• First Posted: April 28, 2022
• Last Update Posted: March 31, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Sarcoidosis; Lymphoproliferative Disorders; Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs