Single Escalating Dose Pilot Trial of Canakinumab (ILARIS®) in Duchenne Muscular Dystrophy

A Single Escalating Dose Pilot Trial of Canakinumab (ILARIS®) Assessing Safety and Biomarker Changes in Boys With Duchenne Muscular Dystrophy

Canakinumab is an anti-interleukin 1 beta (IL1β) antibody approved for use in young children with familial Mediterranean fever, systemic onset juvenile idiopathic arthritis and TNF-receptor associated periodic fever syndrome. This study is a pilot trial to investigate the effects of canakinumab on clinical safety and potential clinical efficacy as demonstrated by short-term changes in select serum biomarkers in a sample of young boys with DMD who are most likely to have high levels of muscle inflammation. Steroid naive DMD subjects aged greater than or equal to 2 years old to less than 6 years old will receive a single subcutaneous dose of canakinumab and undergo safety and serum biomarker monitoring for 30 days. The first 3 subjects will receive 2 mg/kg and if well tolerated, the second 3 subjects will receive 4 mg/kg.

Study Overview

• Status: Active, not recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Canakinumab Injection [Ilaris]

Detailed Description

The study is an open-label, single ascending dose study to assess safety and to evaluate short-term changes in biomarkers. The first 3 boys will receive canakinumab at a dose of 2 mg/kg, and the second 3 will receive a dose of 4 mg/kg. The study is comprised of four visits: a screening visit with baseline lab assessment, treatment day, a 10-14 day post-treatment evaluation with safety labs, and a 30 day post-treatment evaluation with safety labs. There will be a phone assessment on day 3-5 after treatment to screen for any side effects.

Clinical evaluation will screen for clinical AEs and SAEs. If dose escalation (4 mg/kg) must be terminated due to dose-limiting toxicities, the remaining subjects may be enrolled to evaluate the safety of canakinumab at the lower dose level (2 mg/kg).

One blood draw will occur after consent at least 48 hours prior to treatment day and on days 10-14 and 30 after the canakinumab injection to screen for laboratory abnormalities and collect serum for biomarker analysis. After obtaining consent, prior to treatment, 2 red top and 1 purple top 4 cc tubes will be obtained for screening labs and serum biomarker collection. Tuberculosis screening (Quantiferon-Gold) will use 4 blood tubes (grey, yellow, purple, green) with 1 cc of blood in each. At the following 2 visits with blood draws, two red top and one purple top collection tubes of 4 cc will be collected per subject. For red top blood collection tubes, one tube will be sent to the clinical lab for safety lab processing. The second tube will be processed in the research lab for serum biomarkers.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Christopher Spurney, MD; Phone Number: 2024762020; Email: cspurney@childrensnational.org
• Study Contact Backup: Name: Jessica Chong, PA; Email: jchong2@childrensnational.org

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject's parent or legal guardian has provided written informed consent/HIPAA authorization prior to any study-related procedure
• Subject has a diagnosis of DMD
• Subject is ≥ 2 years of age at time of enrollment in the study
• Subject is naïve to treatment with glucocorticoids for DMD
• Subject is ambulatory
• Clinical laboratory test results are within the normal range at the Screening Visit, or if abnormal, are not clinically significant (includes less than 5x normal for AST and ALT), in the opinion of the Investigator. TB serology is negative.
• Subject and parent/guardian are willing and able to comply with, drug administration plan, and follow up visits.

Exclusion Criteria:

• Subject is <2 years of age
• Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
• Subject has current or history of chronic systemic fungal or viral infections;
• Subject has had an acute illness within 4 weeks prior to the first dose of study medication;
• Subject received live vaccination within the previous month
• Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
• Subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents [Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for indication other than DMD for no longer than 3 months cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis. Inhaled and/or topical glucocorticoids prescribed for an indication other than DMD are permitted but must be administered at stable dose for at least 3 months prior to study drug administration];
• Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;
• Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the start of study treatment; Note: Any parameter/test may be repeated at the Investigator's discretion during Screening to determine reproducibility. In addition, subjects may be rescreened if ineligible due to a transient condition which would prevent the subject from participating, such as an upper respiratory tract infection or injury.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Canakinumab treatment	Drug: Canakinumab Injection [Ilaris]; Subject receives subcutaneous injection of canakinumab 2 mg/ kg or 4 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical adverse events	Monitor for changes in health status related to medication use	2 weeks
Laboratory adverse events	Monitor for changes in laboratory results related to medication use	2 weeks
Clinical adverse events	Monitor for changes in health status related to medication use	4 weeks
Laboratory adverse events	Monitor for changes in laboratory results related to medication use	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum biomarkers of inflammation after treatment	Monitor serum biomarker changes associated with anti-inflammatory properties including CD23, Protein C, CCL22, lymphotoxin a1/b1, CD49a, Ly9 and MMP-9, 12 and compare to baseline levels to demonstrate increase or decrease in biomarker levels	2 weeks
Changes in serum biomarkers of inflammation after treatment	Monitor serum biomarker changes associated with anti-inflammatory properties including CD23, Protein C, CCL22, lymphotoxin a1/b1, CD49a, Ly9 and MMP-9, 12 and compare to baseline levels to demonstrate increase or decrease in biomarker levels	4 weeks

Collaborators and Investigators

• Sponsor: Children's National Research Institute
• Collaborators: Foundation to Eradicate Duchenne
• Investigators: Principal Investigator: Christopher Spurney, Children's National Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: May 1, 2019
• First Posted (Actual): May 3, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; Canakinumab
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: 10234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No