Eine Studie zur Bewertung der Wirksamkeit und Sicherheit von Risdiplam als Frühintervention bei pädiatrischen Teilnehmern mit spinaler Muskelatrophie nach Gentherapie (HINALEA 1)
Eine offene Phase-IV-Studie zur Bewertung der Wirksamkeit und Sicherheit von Risdiplam, das als Frühintervention bei pädiatrischen Patienten mit spinaler Muskelatrophie nach Gentherapie verabreicht wird
This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered as an early intervention in pediatric participants with spinal muscular atrophy (SMA) and 2 SMN2 copies who have previously received onasemnogene abeparvovec. Participants are children < 2 years of age genetically diagnosed with SMA.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 4
Kontakte und Standorte
Studienkontakt
- Name: Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry
Studieren Sie die Kontaktsicherung
- Name: Reference Study ID Number: BN44620 https://forpatients.roche.com/ No attachments to email below.
- Telefonnummer: 888-662-6728 (U.S. Only)
- E-Mail: global-roche-genentech-trials@gene.com
Studienorte
-
-
-
Berlin, Deutschland, 13353
- Rekrutierung
- Charité - Universitätsmedizin Berlin SPZ Abteilung Neuropaediatrie
-
Giessen, Deutschland, 35392
- Rekrutierung
- UKGM Standort Gießen
-
-
-
-
-
Uniwersyteckie Centrum Kliniczne, Polen, 80-952
- Rekrutierung
- Uniwersyteckie Centrum Kliniczne
-
Warsaw, Polen, 04-730
- Rekrutierung
- Instytut Pomnik Centrum Zdrowia Dziecka
-
-
-
-
Arkansas
-
Little Rock, Arkansas, Vereinigte Staaten, 72103
- Rekrutierung
- University of Arkansas for Medical Sciences
-
-
Colorado
-
Aurora, Colorado, Vereinigte Staaten, 80045
- Rekrutierung
- Children's Hospital of Colorado
-
-
Florida
-
Gainesville, Florida, Vereinigte Staaten, 32610
- Rekrutierung
- University of Florida Pediatrics
-
-
Georgia
-
Atlanta, Georgia, Vereinigte Staaten, 30329-2309
- Rekrutierung
- Children's Healthcare of Atlanta Center for Advanced Pediatrics
-
-
Illinois
-
Chicago, Illinois, Vereinigte Staaten, 60611
- Zurückgezogen
- Ann and Robert H. Lurie Children Hospital of Chicago
-
-
Michigan
-
Grand Rapids, Michigan, Vereinigte Staaten, 49503
- Zurückgezogen
- Helen DeVos Children's Hospital at Spectrum Health
-
-
New York
-
New York, New York, Vereinigte Staaten, 10032
- Zurückgezogen
- Columbia University Medical Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Vereinigte Staaten, 19104
- Zurückgezogen
- Children'S Hospital of Philadelphia
-
-
Texas
-
Dallas, Texas, Vereinigte Staaten, 75390
- Rekrutierung
- The University of Texas Southwestern Medical Center at Dallas
-
Fort Worth, Texas, Vereinigte Staaten, 76104
- Rekrutierung
- Cook Children's Jane and John Justin Neurosciences Center
-
-
Virginia
-
Norfolk, Virginia, Vereinigte Staaten, 23510
- Zurückgezogen
- Children's Hospital of the King's Daughter
-
-
-
-
-
London, Vereinigtes Königreich, WC1N 3JH
- Rekrutierung
- Great Ormond Street Hospital For Children
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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, but not more than months 30 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
- Has, in the opinion of the investigator, not experienced clinically significant decline in function from the time of onasemnogene abeparvovec administration
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
- Participants requiring awake non-invasive ventilation or with awake hypoxemia (Arterial Oxygen Saturation [SaO2] <95%) with or without ventilator support
- 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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Risdiplam
Participants will receive risdiplam orally once daily for 72 weeks (Treatment Period). The Treatment Period will be followed by a 1-year Treatment Extension Period for a total study duration of 120 weeks (approximately 2.5 years) for each participant enrolled. |
Participants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
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
Zeitfenster: Baseline, Week 72
|
The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement. |
Baseline, Week 72
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Prozentsatz der Teilnehmer mit unerwünschten Ereignissen
Zeitfenster: Bis zu 120 Wochen
|
Bis zu 120 Wochen
|
|
Prozentsatz der Teilnehmer mit schwerwiegenden unerwünschten Ereignissen
Zeitfenster: Bis zu 120 Wochen
|
Bis zu 120 Wochen
|
|
Prozentsatz der Teilnehmer, bei denen die Behandlung aufgrund unerwünschter Ereignisse abgebrochen wurde
Zeitfenster: Bis zu 120 Wochen
|
Bis zu 120 Wochen
|
Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Prozentsatz der Teilnehmer innerhalb des 3. Perzentils des normalen Gewichts-Alter-Bereichs nach 72 Wochen Risdiplam-Behandlung und im Laufe der Zeit
Zeitfenster: Vom Ausgangswert bis zur 120. Woche
|
Vom Ausgangswert bis zur 120. Woche
|
|
|
Prozentsatz der Teilnehmer innerhalb des 3. Perzentils des normalen Bereichs für Länge/Körpergröße im Verhältnis zum Alter nach 72 Wochen Risdiplam-Behandlung und im Laufe der Zeit
Zeitfenster: Vom Ausgangswert bis zur 120. Woche
|
Vom Ausgangswert bis zur 120. Woche
|
|
|
Prozentsatz der Teilnehmer innerhalb des 3. Perzentils des Normalbereichs für Gewicht zu Länge/Größe nach 72 Wochen Risdiplam-Behandlung und im Laufe der Zeit
Zeitfenster: Vom Ausgangswert bis zur 120. Woche
|
Vom Ausgangswert bis zur 120. Woche
|
|
|
Anzahl der respiratorischen Krankenhauseinweisungen während der 72-wöchigen Risdiplam-Behandlung und im Zeitverlauf
Zeitfenster: Bis zu 120 Wochen
|
Bis zu 120 Wochen
|
|
|
Change from Baseline in Bulbar/Swallowing Function Assessment as Measured by the Oral and Swallowing Abilities Tool (OrSAT) at 72 Weeks of Risdiplam Treatment and Over Time
Zeitfenster: From baseline up to Week 120
|
The OrSAT is a validated assessment composed of a checklist of 12 questions assessing aspects of swallowing abilities thought to be clinically meaningful for a type 1 SMA population and developmentally appropriate for infants during the first months of life. Each item is graded with a score of 0 or 1, depending on the child's ability to perform the activity. As some items are age-dependent, the number of items to be used, and therefore the maximum score, changes with increasing age. In the infants younger than 6 months the maximum score is 7. For those between 6 and 9 months, maximum score is 10. For infants of 10 months or older, maximum total score is 12. |
From baseline up to Week 120
|
|
Change in Swallowing Function Assessment as Measured by the Pediatric Functional Oral Intake Scale (p-FOIS) at 72 Weeks of Risdiplam Treatment and Over Time
Zeitfenster: From baseline up to Week 120
|
The p-FOIS is a 6-point scale that assesses feeding ability, 1= Nothing by mouth, 2= Tube dependent for all nutrition/hydration needs with minimal attempts at oral intake for experience and/or pleasure, 3= Tube dependent with consistent intake of food and/or fluid that meets some of the nutrition/hydration needs, 4= Total oral intake but special preparation required, e.g., thickened fluids, puréed diet (where not age-appropriate), 5= Total oral intake but requiring special conditions/modification, e.g., slow flow teat/side lying/pacing or specific food limitations, 6= Total, age-appropriate, oral intake with no restrictions. Higher score indicates higher level of function. |
From baseline up to Week 120
|
|
Change from Baseline in the Raw Score of BSID-III Gross Motor Score Over Time Under Risdiplam Treatment
Zeitfenster: From baseline up to Week 120
|
The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement. |
From baseline up to Week 120
|
|
Percentage of Participants With a Gross Motor Index Between 80-109 as Measured by the Peabody Developmental Motor Scale, Third Edition (PDMS-3) at 72 Weeks of Risdiplam Treatment and Over Time
Zeitfenster: From baseline up to Week 120
|
The PDMS-3 is used to assess gross- and fine-motor skills in children from birth to 5 years. The PDMS-3 has 3 composite scores: Total Motor (combined scores of the core subtests) and two domain composites (Gross Motor and Fine Motor). By combining the results of subtests, these composite scores are considered to have stronger and better indexes of performance and, therefore, more reliable and valid than the subtests. Score for composite indexes range from <70 (impaired or delayed) to >129 (gifted or very advanced). Score of 80-89 indicate below average and 90-109 indicate average skills. |
From baseline up to Week 120
|
|
Percentage of Participants With a Fine Motor Index Between 80-109 as Measured by the PDMS-3 at 72 Weeks of Risdiplam Treatment and Over Time
Zeitfenster: From baseline up to Week 120
|
The PDMS-3 is used to assess gross- and fine-motor skills in children from birth to 5 years. The PDMS-3 has 3 composite scores: Total Motor (combined scores of the core subtests) and two domain composites (Gross Motor and Fine Motor). By combining the results of subtests, these composite scores are considered to have stronger and better indexes of performance and, therefore, more reliable and valid than the subtests. Score for composite indexes range from <70 (impaired or delayed) to >129 (gifted or very advanced). Score of 80-89 indicate below average and 90-109 indicate average skills. |
From baseline up to Week 120
|
|
Change in World Health Organization (WHO) Motor Milestone Achievement at 72 Weeks of Risdiplam Treatment and Over Time
Zeitfenster: From baseline up to Week 120
|
The WHO motor milestones evaluate gross motor development and comprise the time windows of achievement for six gross motor milestones based on data derived from the WHO Multicenter Growth Reference Study (MGRS). The six gross motor milestones are as follows: sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone, and walking alone. A yes response indicates that the participant reached a particular development milestone. |
From baseline up to Week 120
|
|
Percentage of Participants With Improvement or No Change in Respiratory Illness as Assessed by Clinical Global Impression of Change (CGI-C)
Zeitfenster: As per respiratory event on Day 10 and Day 20 post-event (up to Week 120)
|
In a case of respiratory illness during the study, a range of clinical domain level items will be completed by the investigator, as needed. The CGI-C is a single item measure of change using seven response options: "Very much improved," "Much improved," "Minimally improved," "No change," "Minimally worse," "Much worse," and "Very much worse." |
As per respiratory event on Day 10 and Day 20 post-event (up to Week 120)
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienleiter: Clinical Trials, Hoffmann-La Roche
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- BN44620
- 2023 (US NIH Stipendium/Vertrag)
- 2023-504508-26-00 (Ctis)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
This clinical trial evaluates treatment of a rare genetic disease in a small cohort of participants. No data is planned to be shared in order to protect and maintain participant privacy/confidentiality.
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .