RecruitingPhase 4NCT05861999

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

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


Sponsor

Hoffmann-La Roche

Enrollment

28 participants

Start Date

Aug 14, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 3 MonthsMax Age: 24 Months

Inclusion Criteria7

  • <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.

Exclusion Criteria8

  • 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.

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Interventions

DRUGRisdiplam

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


Locations(19)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Valley Children's Hospital

Madera, California, United States

Stanford Univ Medical Center

Palo Alto, California, United States

Children's Hospital of Colorado

Aurora, Colorado, United States

University of Florida Pediatrics

Gainesville, Florida, United States

Children's Healthcare of Atlanta Center for Advanced Pediatrics

Atlanta, Georgia, United States

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Children'S Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Children's Hospital of the King's Daughter

Norfolk, Virginia, United States

Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie

Berlin, Germany

UKGM Standort Gießen

Giessen, Germany

Soroka Medical Center

Beersheba, Israel

Schneider Children's Medical Center of Israel

Petah Tikva, Israel

Sourasky MC, Dana-Dwek Children's Hospital

Tel Aviv, Israel

Uniwersyteckie Centrum Kliniczne

Gdansk, Poland

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, Poland

Sidra Medicine

Al Rayyan, Qatar

Great Ormond Street Hospital For Children

London, United Kingdom

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NCT05861999


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