An Open-label Study to Assess the Efficacy and Safety of Satralizumab in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy Clinical Trial

— SHIELD DMD  

Official title:

A Phase II Multicenter, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Pediatric Patients With Duchenne Muscular Dystrophy (SHIELD DMD)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06450639
• Other study ID #: BN45398
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 30, 2024
• Est. completion date: June 30, 2027

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BN45398 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S.)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of satralizumab, a humanized anti-interleukin-6 receptor (aIL-6R) monoclonal antibody, in ambulatory and non-ambulatory patients with Duchenne muscular dystrophy (DMD) age ≥ 8 to < 16 years old receiving corticosteroid therapy.

Description:

Participants will be included in two groups: those presenting with fractures at baseline and those that are fracture naive at baseline.

The study will assess the potential of satralizumab to improve bone fragility and to increase muscle function.

A weight tier based dose of satralizumab will be given by subcutaneous injection every 4 weeks

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 8 Years to 15 Years

Eligibility

Key Inclusion Criteria:

• Signed Informed Consent Form and Signed Assent Form when appropriate

• Male at birth

• A definitive diagnosis of DMD prior to screening based on documentation of clinical findings and prior confirmatory genetic testing using a clinical diagnostic genetic test.

• Age = 8 and < 16 years at the time of signing Informed Consent Form

• Participants who are fracture-naive are additionally required to meet the following criteria:

• No history of prior low-trauma fractures before the baseline visit nor any radiological findings indicative of prevalent VF at the screening visit

• Be ambulatory, defined as able to walk independently without assistive devices. - Age = 8 to < 12 years old at the time of screening

• Participants with a prior history of low-trauma fractures are additionally required to meet the following criteria:

• Evidence of at least one prevalent vertebral compression fracture of Genant Grade 1 or higher (or radiographic signs of VF) or history of at least one low-trauma long-bone fracture (upper or lower extremity)

• Ambulatory (see above definition) if age = 8 to < 12.

• Non-ambulatory if age = 12 to <16

• Daily oral corticosteroids

Key Exclusion Criteria:

• Major surgery (e.g. spinal surgery) within 3 months prior to Baseline or planned surgery or procedure that would interfere with the conduct of the study for any time during this study •Presence of any clinically significant illness

• Has serological evidence of current, chronic, or active human immunodeficiency virus, tuberculosis, hepatitis C, or hepatitis B infection •Has a symptomatic infection (e.g. upper respiratory tract infection, pneumonia, pyelonephritis, meningitis) within 4 weeks prior to baseline

• Body weight > 100 kg •Treatment with prohibited therapies as defined by the protocol

• Has received a live or live attenuated virus vaccine within 6 weeks of the Baseline visit or expects to receive a vaccination during the first 3 months after Baseline.

• Has abnormal laboratory values considered clinically significant as defined by the protocol

• Any medical condition that might interfere with the evaluation of lumbar spine BMD, such as severe scoliosis or spinal fusion.

• Participant 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

• Participant has an allergy or hypersensitivity to the study medication or to any of its constituents

Other protocol defined inclusion and exclusion criteria may apply

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Satralizumab
Satralizumab will be adminsitered SC in the abdominal or femoral region at a dose of 60 mg (participants weighing below 40 kg) or 120 mg (participants weighing more than or equal to 40 kg and less than or equal to 100 kg) on Day 1 and Weeks 2 and 4 (loading doses) and then Q4W from Weeks 8 to 104 (maintenance doses) until the study completion visit.

Locations

Country	Name	City	State
United States	Children's Hospital of the King's Daughter	Norfolk	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline to Week 52 in Lumbar Spine (LS) Bone Mineral Density (BMD) Z-Score Measured By Dual-Energy X-ray Absorptiometry (DEXA)	BMD of the LS is measured using DEXA	Baseline to Week 52
Secondary	Percentage of Participants with Treatment-Emergent Adverse Events	An adverse event is any untoward medical occurrence in a patient or clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment	Up to approximately 30 Months
Secondary	Percentage of Participants with Serious Adverse Events	A serious adverse event is defined as any untoward medical occurrence that, at any dose: Results in death, Is life threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent disability or incapacity, Is a congenital anomaly or birth defect, Medically Significant	Up to approximately 30 Months
Secondary	Percentage of Participants with Adverse Events of Special Interest		Up to approximately 30 Months
Secondary	Change from Baseline to Weeks 24 and 52 in LS BMD Z-Score Measured by DEXA		Baseline to Week 24 and Week 52
Secondary	Change from Baseline to Weeks 24 and 52 in Total Body Less Head Bone Mineral Density (TBLH BMD) Z-Score Measured by DEXA		Baseline to Week 24 and Week 52
Secondary	Change from Baseline to Weeks 24 and 52 in Circulating Bone Metabolism Biomarkers	Bone biomarkers are produced from the bone remodeling process and include bone formation biomarkers, bone resorption biomarkers and regulators of bone turnover	Baseline to Week 24 and Week 52
Secondary	Mean Number Per Participants of New Low-Trauma Long-Bone or Vertebral Fractures (VF)	"A low-trauma fracture is defined as one occurring spontaneously or resulting from a fall from a standing height or less, without major trauma or the influence of an external force (e.g. motor vehicle accident)"	Baseline, Week 52 and Week 104
Secondary	Percentage of Participants with New Low-Trauma Long-Bone or VF		Baseline, Week 52 and Week 104
Secondary	Change in Time to Rise From the Floor (RFF) Velocity	The rise from the floor test quantifies the time required for the subject to stand in an upright position with arms by sides, starting from the supine position with arms by sides.	Baseline to Week 52
Secondary	Observed Serum Concentration of Satralizumab at Specified Trough Timepoints Up To Week 104		Up to Week 104
Secondary	Apparent Clearance of Satralizumab	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	Up to Week 104
Secondary	Apparent Volume of Distribution of Satralizumab	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.	Up to Week 104
Secondary	Area Under the Concentration-Time Curve of Satralizumab	Area under the concentration-time curve from time zero to the last quantifiable concentration of Satralizumab in plasma.	Up to Week 104
Secondary	Anti-Drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study		Up to approximately 30 Months