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NCT05861999PHASE4Recruiting

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

Hoffmann-La Roche

Start Date

8/14/2024

Completion Date

3/31/2029

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 Criteria

Age Range: No minimum to No maximum

Inclusion Criteria: * \<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 Criteria: * 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.

Interventions

DRUG

Risdiplam

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Conditions

Muscular Atrophy, Spinal

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas 72103

United States

Valley Children's Hospital

Madera, California 93636

United States

Stanford Univ Medical Center

Palo Alto, California 94304

United States

Children's Hospital of Colorado

Aurora, Colorado 80045

United States

University of Florida Pediatrics

Gainesville, Florida 32610

United States

Children's Healthcare of Atlanta Center for Advanced Pediatrics

Atlanta, Georgia 30329-2309

United States

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan 49503

United States

Children'S Hospital of Philadelphia

Philadelphia, Pennsylvania 19104

United States

University of Texas Southwestern Medical Center

Dallas, Texas 75390

United States

Children's Hospital of the King's Daughter

Norfolk, Virginia 23510

United States

Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie

Berlin, 13353

Germany

UKGM Standort Gießen

Giessen, 35392

Germany

Soroka Medical Center

Beersheba, 8410101

Israel

Schneider Children's Medical Center of Israel

Petah Tikva, 4920235

Israel

Sourasky MC, Dana-Dwek Children's Hospital

Tel Aviv, 6423906

Israel

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-952

Poland

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, 04-730

Poland

Sidra Medicine

Al Rayyan,

Qatar

Great Ormond Street Hospital For Children

London, WC1N 3JH

United Kingdom