Phase 1/2a for Safety, PK and PD of SQY51 in Paediatric and Adult Patients Duchenne Muscular Dystrophy

NCT05753462 | Recruiting Phase 1 DMC

• 2 other identifiers: AVANCE1-1/2a2022-500703-49-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy; Duchenne; Dystrophin; DMD; Exon skipping; Exon 51; ASO therapeutics; Tricyclo-DNA

Outcome Measures

Primary Outcomes (1)

• Incidence of AEs in all participants

  From baseline up to week 49

Secondary Outcomes (3)

• 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

Study Arms (4)

Phase 1

EXPERIMENTAL

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

Phase 2a - Treatment arm (Dose 1)

EXPERIMENTAL

Non randomized participants will receive by IV dose 1 of SQY51 in 4 blocks of 4-weeks.

Drug: Phase 2a, SQY51 (cohort 1)

Phase 2a - Treatment arm (Dose 2)

EXPERIMENTAL

Non randomized participants will receive by IV dose 2 of SQY51 in 4 blocks of 4-weeks.

Drug: Phase 2a, SQY51 (cohort 2)

Phase 2a - Treatment arm (Dose 3)

EXPERIMENTAL

Non randomized participants will receive by IV dose 3 of SQY51 in 4 blocks of 4-weeks.

Drug: Phase 2a, SQY51 (cohort 3)

Interventions

Phase 1, SQY51 DRUG

SQY51 is administered by intravenous infusion.

Phase 1

Phase 2a, SQY51 (cohort 1) DRUG

SQY51 is administered by intravenous infusion at dose 1

Phase 2a - Treatment arm (Dose 1)

Phase 2a, SQY51 (cohort 2) DRUG

SQY51 is administered by intravenous infusion at dose 2.

Phase 2a - Treatment arm (Dose 2)

Phase 2a, SQY51 (cohort 3) DRUG

SQY51 is administered by intravenous infusion at dose 3.

Phase 2a - Treatment arm (Dose 3)

Eligibility Criteria

• Age: 6 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Boys of ≥6 years of age and ≥ 16 kg body weight.
• Ambulatory or non-ambulatory status,
• 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.
• Diagnosed with Duchenne Muscular Dystrophy (DMD), genotypically confirmed with DMD mutations amenable to exon-51 skipping.
• Stable hepatic and renal function.
• Left ventricular ejection fraction (LVEF) at screening ≥40%.
• 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.
• Non-invasive mechanical ventilation is permissive if \< 16 h/day.
• Being affiliated with a French social security.
• Informed consent form signed by the patient or, if minor, by the legal guardian(s).
• Patients must have completed Phase 1 of the study.

You may not qualify if:

• 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.
• 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).
• 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.
• Patient that received gene therapy.
• Patient with intellectual disability or behavioral problem such that they cannot comply with the study procedure.
• Patient with advanced cardiomyopathy and LVEF \< 40%. Patients with dysrhythmias and being treated for dysrhythmias. Patients with non-treated tachycardia.
• Patient for which orthopedic surgery is planned during the time of the study.
• 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.
• Patients on medications that can restore dystrophin expression, tamoxifen and other drugs without indication for DMD or paediatric population.
• Abnormal laboratory values in the clinically significant range.

Sponsors & Collaborators

• Sqy Therapeutics: lead
• Biotrial: collaborator

Study Sites (1)

Hôpital Raymond Poincaré

Garches, 92380, France

RECRUITING

Related Publications (33)

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MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

Clinical Trials, Phase I as Topic

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Central Study Contacts

Marine Geoffroy-Guiraud, PhD

CONTACT

+33 7 65 20 90 85; info@sqy-synthena.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2023
• First Posted: March 3, 2023
• Study Start: April 26, 2023
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: April 1, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)