AVANCE1: Phase 1/2a for Safety, PK and PD of SQY51 in Paediatric and Adult Patients Duchenne Muscular Dystrophy
Study Details
Study Description
Brief Summary
This is a Phase 1/2a, monocentric, open label study to evaluate the safety, pharmacokinetics, and pharmacodynamics of SQY51 in patients with Duchenne muscular dystrophy
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
Avance1 is a Phase 1/2a, Monocentric, Open Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of SQY51 in 12 patients with a genetically confirmed diagnosis of Duchenne muscular dystrophy, This study will include i) 13-week Phase 1 Multiple Dose Escalation Phase, and a ii) 32-week Phase 2a.
Twelve (12) patients ≥ 6 years, both ambulant and non-ambulant, will be sequentially enrolled in phase 1 and will receive escalating doses of SQY51 once every two weeks. In phase 2a, patients will be allocated in three cohorts in a non-randomized manner.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Phase 1 Participants will receive single escalating doses of 2, 4, 6, 10, 16 and 25 mg/kg by intravenous infusion of SQY51 every 2 weeks. |
Drug: Phase 1, SQY51
SQY51 is administered by intravenous infusion.
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Experimental: Phase 2a - Treatment arm (Dose 1) Non randomized participants will receive by IV dose 1 of SQY51 in 4 blocks of 4-weeks. |
Drug: Phase 2a, SQY51 (cohort 1)
SQY51 is administered by intravenous infusion at dose 1
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Experimental: Phase 2a - Treatment arm (Dose 2) Non randomized participants will receive by IV dose 2 of SQY51 in 4 blocks of 4-weeks. |
Drug: Phase 2a, SQY51 (cohort 2)
SQY51 is administered by intravenous infusion at dose 2.
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Experimental: Phase 2a - Treatment arm (Dose 3) Non randomized participants will receive by IV dose 3 of SQY51 in 4 blocks of 4-weeks. |
Drug: Phase 2a, SQY51 (cohort 3)
SQY51 is administered by intravenous infusion at dose 3.
|
Outcome Measures
Primary Outcome Measures
- Incidence of AEs in all participants [From baseline up to week 49]
Secondary Outcome Measures
- Pharmacokinetic plasma concentration of SQY51 (µg/ml) [From baseline up to week 49]
- Change from baseline in time to rise from floor, time to complete 1-min, 6-min and 10-min walk in ambulant patients as well as MFM and PUL scores in both ambulant and non-ambulant patients [From baseline up to week 49]
- Changes from baseline in skeletal muscle dystrophin expression [From baseline up to week 49]
Eligibility Criteria
Criteria
INCLUSION CRITERIA FOR PHASE 1:
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Boys of ≥6 years of age and ≥ 16 kg body weight.
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Ambulatory or non-ambulatory status,
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Patients and, if minor, their legal guardians, who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
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Diagnosed with Duchenne Muscular Dystrophy (DMD), genotypically confirmed with DMD mutations amenable to exon-51 skipping.
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Stable hepatic and renal function.
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Left ventricular ejection fraction (LVEF) at screening ≥40%.
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If clinically indicated, approved concomitant treatment within standards of care guidelines for DMD, such as antihypertensive, vasodilators, lipid lowering, thyroid replacement, vitamins, mineral substitution, gastric protectors, and nutritional supplements.
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Non-invasive mechanical ventilation is permissive if < 16 h/day.
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Being affiliated with a French social security.
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Informed consent form signed by the patient or, if minor, by the legal guardian(s).
INCLUSION CRITERIA FOR PHASE 2a:
Patients must have completed Phase 1 of the study.
EXCLUSION CRITERIA FOR PHASE 1 AND 2a:
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Patient with any serious medical/surgical or psychiatric condition/illness/history that in the opinion of the investigator would jeopardize patient's safety or would interfere with the study assessments/results, including insufficient vaccination against infectious diseases as recommended by national guidelines, medical history of infection with Hepatitis B,C and HIV.
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Patient with any known allergies to products likely to be used in the study (e.g., antiseptics, anesthetics), known hypersensitivity to any of the ingredients, or excipients of the study drug).
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Patient who participated in other investigational study within the last three months, including those with investigational drugs that aim at restoring dystrophin expression such as other antisense oligomers.
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Patient that received gene therapy.
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Patient with intellectual disability or behavioral problem such that they cannot comply with the study procedure.
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Patient with advanced cardiomyopathy and LVEF < 40%. Patients with dysrhythmias and being treated for dysrhythmias. Patients with non-treated tachycardia.
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Patient for which orthopedic surgery is planned during the time of the study.
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Tracheostomized patients and dependent on invasive mechanical ventilation. Non-invasive mechanical ventilation ≥ 16 h/day. Predicted vital forced capacity < 20%. Medical history with more than two respiratory decompensations requiring hospitalization during the previous year. No respiratory decompensation in the four months preceding enrolment.
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Patients on medications that can restore dystrophin expression, tamoxifen and other drugs without indication for DMD or paediatric population.
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Abnormal laboratory values in the clinically significant range.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Hôpital Raymond Poincaré | Garches | France | 92380 |
Sponsors and Collaborators
- Sqy Therapeutics
- Biotrial
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
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- AVANCE1-1/2a
- 2022-500703-49-01