A Study Evaluating the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients With Spinal Muscular Atrophy Who Experienced a Plateau or Decline in Function After Gene Therapy

Официальное название

A Phase IV Open-Label Study Evaluating the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients With Spinal Muscular Atrophy Who Experienced a Plateau or Decline in Function After Gene Therapy

Обзор

This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered in pediatric participants with SMA and 2 SMN2 copies who previously received onasemnogene abeparvovec and experience a plateau or decline in function. Participants to be enrolled are children \<2 years of age genetically diagnosed with SMA.

Вмешательства

• Препарат Risdiplam
  Participants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.

Первичные конечные точки

• Change from Baseline in the Raw Score of Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) Gross Motor Score at 72 Weeks of Risdiplam Treatment [Срок оценки: Baseline, Week 72]

Вторичные конечные точки (3)

• Percentage of Participants With Adverse Events [Срок оценки: Up to 120 weeks]
• Percentage of Participants With Serious Adverse Events [Срок оценки: Up to 120 weeks]
• Percentage of Participants With Treatment Discontinuation Due to Adverse Events [Срок оценки: Up to 120 weeks]

Критерии участия

Критерии включения

• <2 years of age at the time of informed consent
• Confirmed diagnosis of 5q-autosomal recessive SMA, including genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the Survival of Motor Neuron 1 (SMN1) gene
• Confirmed presence of two SMN2 gene copies as documented through laboratory testing
• Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically
• Has received onasemnogene abeparvovec for SMA no less than 13 weeks prior to enrollment
• If treated with risdiplam prior to onasemnogene abeparvovec, risdiplam treatment must not have exceeded 3 weeks and must be discontinued 1 day prior to onasemnogene abeparvovec administration.
• In the opinion of the investigator, has demonstrated a plateau or decline in function post-gene therapy (with a duration of 26 weeks or less) documented by 2 individual time points in the functions as follows: swallowing AND one additional function/ability (respiratory, motor function, other) per appropriate expectation.

Критерии исключения

• Previous or current enrolment in investigational study prior to initiation of study treatment
• Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
• Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide
• Concomitant or previous use of an anti-myostatin agent
• Participants requiring invasive ventilation or tracheostomy
• Presence of feeding tube and an OrSAT score of 0
• Hospitalization for pulmonary event within the last 2 months, or any planned hospitalization at the time of screening
• Any major illness requiring hospitalization within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to first dose administration.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• University of Arkansas for Medical Sciences — Little Rock
• Valley Children's Hospital — Madera
• Stanford Univ Medical Center — Palo Alto
• Children's Hospital of Colorado — Aurora
• University of Florida Pediatrics — Gainesville
• Children's Healthcare of Atlanta Center for Advanced Pediatrics — Atlanta
• Helen DeVos Children's Hospital at Spectrum Health — Grand Rapids
• Children'S Hospital of Philadelphia — Philadelphia
• … и ещё 2 центра

Израиль · 3 центра

• Soroka Medical Center — Beersheba
• Schneider Children's Medical Center of Israel — Petah Tikva
• Sourasky MC, Dana-Dwek Children's Hospital — Tel Aviv

Германия · 2 центра

• Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie — Berlin
• UKGM Standort Gießen — Giessen

Польша · 2 центра

• Uniwersyteckie Centrum Kliniczne — Gda?sk
• Instytut Pomnik Centrum Zdrowia Dziecka — Warsaw

Катар · 1 центр

• Sidra Medicine — Al Rayyan

Великобритания · 1 центр

• Great Ormond Street Hospital For Children — London

Идентификаторы

NCT: NCT05861999 · BN44621 · 2023-505161-81-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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