Evaluation of Satralizumab Efficacy and Safety in Pediatric Duchenne Muscular Dystrophy: A Phase II Multicenter, Open-Label Study

Trial ID: 2024-512383-65-00
Protocol: BN45398
Sponsor: F. Hoffmann-La Roche AG

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Diseases & Conditions

Duchenne muscular dystrophy

Objectives

The primary objective of this study is to evaluate the **efficacy** of satralizumab in improving bone mineral density (BMD) in fracture-naïve participants with Duchenne Muscular Dystrophy (DMD), as assessed by dual-energy X-ray absorptiometry (DEXA). This is clinically relevant as DMD patients often experience reduced BMD, leading to an increased risk of fractures, and improving BMD could potentially enhance their quality of life and reduce fracture incidence.

Secondary objectives include:

To evaluate the safety of satralizumab in DMD patients.
To assess the efficacy of satralizumab in BMD across all participants using DEXA.
To evaluate the efficacy of satralizumab on bone metabolism biomarkers in all participants.
To assess the efficacy of satralizumab in reducing the incidence of fractures.
To characterize the pharmacokinetics of satralizumab.
To evaluate the immunogenicity of satralizumab.
To assess the efficacy of satralizumab on bone metabolism biomarkers in participants without prior fractures.

Participants

The clinical trial involves a total of **25 participants** diagnosed with **Duchenne Muscular Dystrophy (DMD)**. The study population consists exclusively of male subjects, aged between 8 and 18 years, who are either ambulatory or non-ambulatory. Participants were selected based on specific criteria, including being fracture-naïve or having a history of low-trauma fractures. All participants are required to have been on daily oral corticosteroids for at least 12 months, with a stable dose for at least 12 weeks prior to screening. The trial focuses on a vulnerable population, with considerations for their physical activity levels, as ambulatory participants must be able to walk independently without assistive devices. The study aims to evaluate the efficacy of satralizumab in improving bone mineral density in these individuals.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of **satralizumab** in pediatric patients with Duchenne Muscular Dystrophy (DMD). This is a Phase II, multicenter, open-label study. The trial aims to assess the change in bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA) in fracture-naïve participants. The study is expected to commence recruitment on November 26, 2024, and conclude by July 31, 2027, with a maximum treatment period of 104 weeks.

Participants will be administered **satralizumab** via subcutaneous injection, with a maximum daily dose of 180 mg and a total dose not exceeding 5.04 g. The trial includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The primary endpoint is the change in lumbar spine BMD Z-score from baseline to Week 52. Secondary endpoints include the incidence of treatment-emergent adverse events, changes in vital signs, and other safety assessments.

Participants are expected to be involved in the study for up to 104 weeks. Inclusion criteria require participants to be male, aged 8 to less than 18 years, and on a stable dose of daily oral corticosteroids for at least 12 months. Conditions for early termination from the study include the occurrence of serious adverse events or non-compliance with the study protocol. The study will not be low-intervention, as it is a confirmatory trial for the ongoing development program of the molecule.

Treatment

The clinical trial involves the administration of **Satralizumab**, a humanized anti-IL-6 receptor monoclonal antibody, as the experimental medication. Satralizumab is provided in the form of a **solution for injection** and is administered via **subcutaneous injection**. The maximum daily dose is 180 mg, with a total maximum dose of 5.04 g over the course of the study. The treatment period extends up to 104 weeks. The medication is supplied by F. Hoffmann-La Roche Ltd and is identified by the sponsor product codes RO 533-3787/F01-04 and RO 533-3787/F01-06. The active substance, satralizumab, is derived from a protein of other origin.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab in pediatric patients with Duchenne Muscular Dystrophy. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The study aims to assess the impact of satralizumab on bone mineral density as measured by dual-energy X-ray absorptiometry (DEXA) in fracture-naïve participants.

Efficacy

The efficacy of **Satralizumab** in the clinical trial will be assessed primarily through changes in bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DEXA). The primary endpoint is the change from baseline to Week 52 in lumbar spine (LS) BMD Z-score. Secondary endpoints include changes in LS BMD Z-score at Weeks 24, 52, and 104, as well as changes in total body less head (TBLH) and total hip BMD Z-scores at the same timepoints. Additionally, the trial will evaluate changes in circulating bone metabolism biomarkers at Weeks 12, 24, and 52, and the incidence and proportion of new low-trauma long-bone or vertebral fractures by Weeks 52 and 104.

Data collection will involve the use of DEXA scans to measure BMD Z-scores at specified intervals. The trial will also monitor the incidence of treatment-emergent adverse events, serious adverse events, and adverse events of special interest. Clinically significant changes in vital signs, physical examination findings, safety laboratory assessments, and electrocardiograms (ECGs) will be recorded. The serum concentration of **Satralizumab** will be summarized at specified trough timepoints up to Week 104, and pharmacokinetic parameters such as apparent clearance and volume of distribution will be estimated. The prevalence of anti-drug antibodies (ADAs) at baseline and their incidence during the study will also be assessed.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age ≥ 8 and < 18 years at the time of signing Informed Consent Form
Male at birth
Group 2 participants are required to meet the following criteria: Be fracture naïve, defined as: No history of prior low-trauma fractures before the baseline visit nor any radiological findings indicative of prevalent vertebral fracture (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
Group 1 participants are required to meet the following criteria: – SDI ≤ 3 - Age ≥ 8 to < 18 years old at the time of screening – If ambulatory (defined as able to walk independently without assistive devices) the participant must have a prior history of fractures Prior history of low-trauma fracture defined as: evidence of at least one prevalent vertebral compression fracture of Genant Grade 1 or 2 (or radiographic signs of VF) or history of at least one low-trauma long bone fracture (upper or lower extremity) but no more than two events incurring in low-trauma fractures (at any anatomical site) OR – If non-ambulatory, characterized as being non-ambulatory for a minimum of 6 months with onset of non-ambulatory status defined as participant- or caregiver-reported age of continuous wheelchair use, approximated to the nearest month, and an NSAA walk score of "0" and inability to perform the 10MWR at the baseline visit, the participant can be with or without prevalent fractures at baseline
For ambulatory participants: Group 1 and 2: NSAA total score ≥ 16 as assessed at the screening visit
Daily oral corticosteroids for at least 12 months with a stable dose for at least 12 weeks prior to screening and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the study

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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, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy or concomitant illness or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risks for the participant or a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the subject’s ability to comply with the protocol required testing or procedures or compromise the subject’s wellbeing, safety, or clinical interpretability
Has serological evidence of current, chronic, or active human immunodeficiency virus, 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
History or laboratory evidence of coagulation disorders
Body weight at screening < 20 or > 100 kg