Clinical trial NCT06450639: A Study to Assess the Efficacy and Safety of Satralizumab in Duchenne Muscular Dystrophy (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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: DMD, IL6, IL6R, bone, muscle, fractures, BMD, inflammation
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2024-06-10
Enrollment: 50
Sex: MALE
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 participants with DMD age ≥ 8 to \< 18 years old receiving corticosteroid therapy.

Detailed description: Participants will be included in two groups: ambulatory participants with fractures and non-ambulatory participants with or without a history of fractures (Group 1) and ambulatory participants who are fracture naive (Group 2) 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 (SC) injection every 4 weeks (Q4W).

Eligibility criteria: 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 \< 18 years at the time of signing Informed Consent Form
* Group 1 participants are required to meet the following criteria:

  - Ambulatory (defined as able to walk independently without assistive devices) with a prior history of fractures:
  1. 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) OR
  2. 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 North Star Ambulatory Assessment (NSAA) walk score of "0" and inability to perform the 10-Meter Walk/Run (10 MWR) at the baseline visit, with or without fractures
* 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 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
* 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 (HIV), tuberculosis (TB), 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 at screening \<20 or \> 100 kg
* Evidence of a severe vertebral fracture (VF) (defined as Grade 3), assessed by radiographic imaging at screening and quantified using the Genant semiquantitative method
* 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 LS 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

Primary outcomes:
measure: Group 2: Change From Baseline to Week 52 in Lumbar Spine (LS) Bone Mineral Density (BMD) Z-score Measured by Dual-energy X-ray Absorptiometry (DEXA)
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: All Participants: Change From Baseline to Weeks 24, 52, and 104 in LS BMD Z-score Measured by DEXA
timeFrame: Baseline to Week 24, Week 52 and Week 104
measure: Group 2: Change From Baseline to Weeks 24 and 104 in LS BMD Z-score Measured by DEXA
timeFrame: Baseline to Week 24 and Week 104
measure: Group 2: Change From Baseline to Weeks 24, 52 and 104 in Total Body Less Head Bone Mineral Density (TBLH BMD) Z-score Measured by DEXA
timeFrame: Baseline to Week 24, Week 52 and Week 104
measure: Group 2: Change From Baseline to Weeks 24, 52 and 104 in Total Hip BMD Z-score Measured by DEXA
timeFrame: Baseline to Week 24, Week 52 and Week 104
measure: Group 2: Change From Baseline to Weeks 12, 24 and 52 in Circulating Bone Metabolism Biomarkers
timeFrame: Baseline to Week 12, Week 24 and Week 52
measure: All Participants: Change From Baseline to Weeks 12, 24 and 52 in Circulating Bone Metabolism Biomarkers
timeFrame: Baseline to Week 12, Week 24, and Week 52
measure: All Participants: Mean Number Per Participants of New Low-trauma Long-bone or Vertebral Fractures (VF)
timeFrame: Baseline to Week 52 and Week 104
measure: All Participants: Percentage of Participants With New Low-trauma Long-bone or VF
timeFrame: Baseline to Week 52 and Week 104
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 30 Months
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to approximately 30 Months
measure: Percentage of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: Up to approximately 30 Months
measure: Observed Serum Concentration of Satralizumab at Specified Trough Timepoints up to Week 104
timeFrame: Up to Week 104
measure: Apparent Clearance of Satralizumab
timeFrame: Up to Week 104
measure: Apparent Volume of Distribution of Satralizumab
timeFrame: Up to Week 104
measure: Area Under the Concentration-time Curve of Satralizumab
timeFrame: Up to Week 104
measure: Percentage of Participants With Anti-drug Antibodies (ADAs) at Baseline and During the Study
timeFrame: Up to approximately 30 Months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta Center for Advanced Pediatrics
state: Georgia
city: Worcester
country: United States
facility: University of Massachusetts Memorial Childrens Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Denton
country: United States
facility: Neurology Rare Disease Center
state: Texas
city: Norfolk
country: United States
facility: Child's Hosp King's Daughters
state: Virginia
city: Roma
country: Italy
facility: Policlinico Agostino Gemelli
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico ?Carlo Besta?
state: Lombardia
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lódz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny
city: Esplugues De Llobregas
country: Spain
facility: Hospital Sant Joan De Deu
state: Barcelona
city: Asturias
country: Spain
facility: Hospital U. Central de Asturias
city: Valencia
country: Spain
facility: Hospital Universitario la Fe
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: