Clinical trial NCT06178393: Real-World Use of Novel Treatments in Patients With Spinal Muscular Atrophy (SMA): A Multi-Site Retrospective Chart Review of Pediatric SMA Patients Outside of the United States
Official title: Real-World Use of Novel Treatments in Patients With Spinal Muscular Atrophy (SMA): A Multi-Site Retrospective Chart Review of Pediatric SMA Patients Outside of the United States
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Spinal Muscular Atrophy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-12-21
Enrollment: 162
Sex: ALL
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This was a retrospective, noninterventional cohort study.

Brief summary: This global, retrospective, non-interventional, medical chart review (MCR), descriptive study collected patient-level data in regions outside the US.

The study required a repeated data collection at follow-up dates from start of treatment with nusinersen, onasemnogene abeparvovec-xioi (OA), and/or risdiplam. At the start of data collection, the study team reached out to the health care providers (HCPs) involved in treating pediatric SMA patients for participating in this study. The physicians across the participating countries conducted a retrospective MCR of pediatric patients diagnosed with SMA who were treated with at least 1of the 3 novel disease-modifying treatments (DMTs): nusinersen, OA, and/or risdiplam.

All health care encounters data i.e., emergency and inpatient admissions, surgery, and outpatient consultations of recruited patients, including their treatment with nusinersen, OA, and/or risdiplam, were abstracted to understand the treatment patterns as per routine clinical practice for SMA management globally. The first date of initial administration of 1 of the 3 target drugs was used as the "index date." Based on this, the record abstraction was performed through a retrospective MCR during the pre-index period, at index date and in the post-index period.


Eligibility criteria: Inclusion criteria:

* Genetically confirmed diagnosis of SMA.
* Aged less than 5 years at index date.
* Initiated treatment with nusinersen or onasemnogene abeparvovec-xioi or risdiplam or any combination of them during the identification period.
* Availability of medical information in chart for at least 1 visit prior to initiation of treatment with the target treatment(s).

Exclusion criteria:

None

Primary outcomes:
measure: Number and proportion of male patients
timeFrame: Baseline
measure: Number and proportion of female patients
timeFrame: Baseline
measure: Number and proportion of patients per race
timeFrame: Baseline
measure: Number and proportion of patients per insurance type
timeFrame: Baseline
measure: Number and proportion of patients per gestational age category at birth
timeFrame: Baseline
measure: Number and proportion of patients per country
timeFrame: Baseline
measure: Number and proportion of patients with prenatal screening performed and confirmed for SMA
timeFrame: Baseline
measure: Number and proportion of patients undergoing newborn screening for SMA
timeFrame: Baseline
measure: Number and proportion of patients experiencing SMA-related symptoms prior to initiation of the first DMT (index drug)
timeFrame: Baseline
measure: Mean age at onset of SMA-related symptoms experienced prior to initiation of the first DMT
timeFrame: Baseline
measure: Mean age at SMA genetic diagnosis
timeFrame: Baseline
measure: Number and proportion of patients who had as survival of motor neuron 1 (SMN1) genetic test
timeFrame: Baseline
measure: Number and proportion of patients per SMN1 genetic test result category
timeFrame: Baseline
measure: Number and proportion of patients who had a survival of motor neuron 2 (SMN2) genetic test
timeFrame: Baseline
measure: Number and proportion of patients per SMN2 gene copy number
timeFrame: Baseline
measure: Number and proportion of patients per SMA type at diagnosis
timeFrame: Baseline
measure: Mean body weight
timeFrame: Baseline
Secondary outcomes:
measure: Time to first improvement from last pre-index/pre-switch assessment
timeFrame: Up to approximately 5 years
measure: Time from pre-index/last pre- switch until the last follow-up visit with available data for the overall developmental motor milestones rates
timeFrame: Up to approximately 5 years
measure: Number and proportion of patients who achieved at least once ≥ 1 point increase on the Hammersmith infant neurological examination: Section 2 (HINE-2, motor milestones)
timeFrame: Up to approximately 5 years
measure: Number and proportion of patients who achieved at least once ≥ 3 points increase on the Hammersmith Functional Motor Scale-Expanded (HFMSE)
timeFrame: Up to approximately 5 years
measure: Number and proportion of patients who achieved at least once ≥ 3 points decrease on the HFMSE
timeFrame: Up to approximately 5 years
measure: Number and proportion of patients who maintained score change ±3 points on the HFMSE
timeFrame: Up to approximately 5 years
measure: Change in score per month on the HFMSE
timeFrame: Baseline up to approximately 5 years
measure: Estimate of HFMSE score per timepoint during the post period, adjusted for the last pre-value
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who achieved at least once ≥ 1 point increase on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND)
timeFrame: Up to approximately 5 years
measure: Number and proportion of patients who achieved at least once ≥4 points increase on the CHOP INTEND
timeFrame: Up to approximately 5 years
measure: Change in score per month on the CHOP INTEND
timeFrame: Baseline up to approximately 5 years
measure: Estimate of score per timepoint during the post period, adjusted for the last pre-value on the CHOP INTEND
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients without any craniofacial deficits during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who exhibited at least 1 craniofacial deficit during the post-index period including reduced mouth opening, overbite, narrow/high arched palate, and other craniofacial deficits
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who remained free of any non-oral support during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who did not remain free of any non-oral support during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who exhibited constipation at least once during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who exhibited failure to thrive or underweight at least once during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients per the Pediatric-Functional Oral Intake Scale (p-FOIS) score at the timepoints of interest
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who had improvement (the p-FOIS score increased by at least 1 point between the timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who had decline (the p-FOIS score decreased by at least 1 point between the timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (the p-FOIS score maintained stable between the timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with unknown status (unknown/missing p-FOIS score in any of the timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with p-FOIS <3 at the timepoints of interest in the functional swallow category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with p-FOIS ≥ 3 at the timepoints of interest in the functional swallow category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who achieved (patients who went from the p-FOIS < 3 to the p-FOIS ≥ 3 category between the timepoints of interest) in the functional swallow category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who lost (patients who went from the p-FOIS ≥ 3 to p-FOIS <3 category between the timepoints of interest) in the functional swallow category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients who remained at p-FOIS <3 category between the timepoints of interest) in the functional swallow category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients who remained at p-FOIS ≥ 3 category between the timepoints of interest) in the functional swallow category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with unknown (unknown/missing p-FOIS score in any of the timepoints of interest) in the functional swallow category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with p-FOIS <4 at the timepoints of interest in the total oral nutrition category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with p-FOIS ≥ 4 at the timepoints of interest in the total oral nutrition category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who achieved (patients who went from the p-FOIS <4 to p-FOIS ≥ 4 category between the timepoints of interest) in the total oral nutrition category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who lost (patients who went from the p-FOIS ≥ 4 to p-FOIS <4 category between the timepoints of interest) in the total oral nutrition category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients who remained at p-FOIS< 4 category between the timepoints of interest) in the total oral nutrition category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients who remained at p-FOIS≥ 4 category between the timepoints of interest) in the total oral nutrition category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with unknown status (unknown/missing p-FOIS score in any of the timepoints of interest) in the total oral nutrition category
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients without any swallow evaluation during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients with at least 1 swallow evaluation during the post index period including the type of swallow evaluation
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients with at least 1 symptom of interest related to eating during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients without any sign of aspiration during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients with at least 1 aspiration sign during the post-index period for each of the following consistencies: thin liquids; nectar liquids (mildly thick); honey liquids (moderately thick); puree; solid
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients without any deficits in swallowing during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who exhibited nasal regurgitation at least once during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who exhibited no swallow initiation at least once during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who exhibited pharyngeal residue at least once during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who exhibited aspiration at least once during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who suffered penetration at least once during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who were able to drink thin liquids during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who were able to drink thin nectar during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who were able to drink nectar during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who were able to drink honey during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who reported at least once the following deficits relating to the patients cry/voice during the post-index period: not audible; quiet/weak/hard to hear; wet/gurgly; breathy; unknown/not reported
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who did not experience fatigue with speech over the course of the day during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced at least once fatigue with speech over the course of the day during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced at least once clinical signs of aspiration during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced at least once problem in chewing during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced at least once aversion/disinterest in eating or drinking
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced at least once a concern for insufficient oral nutrient ingestion
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients per category of maximum speech milestone achieved during the post-index period.
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced clinical signs of aspiration at the timepoints of interest
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with improvement (patients who had clinical signs of aspiration at the first timepoint of interest and lost it at the next timepoint of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with decline (patients who didn't have any clinical signs of aspiration at the first timepoint of interest and gained it at the next timepoint of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients without clinical signs of aspiration at both timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients with clinical signs of aspiration at both timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with unknown status (patients with unknown/missing clinical signs of aspiration in any of the timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who experienced fatigue with eating at the timepoints of interest
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with improvement (patients who experienced fatigue with eating at the first timepoint of interest and did not experience it at the next timepoint of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with decline (patients who didn't experience fatigue with eating at the first timepoint of interest and experienced it at the next timepoint of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients who didn't experience fatigue with eating at both timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients who experienced fatigue with eating at both timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with unknown status (patients with unknown/missing experience of fatigue with eating in any of the timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients per each category of maximum speech milestone achieved at the timepoints of interest
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with improvement (patients who had cooing as a maximum speech milestone at the first timepoint of interest and achieved at least 1 more speech milestone at the next timepoint of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with decline in speech milestones
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients who maintained status (patients who remained at cooing between the timepoints of interest or patients who remained at 'consonant and vowel combination' or above between the timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with unknown status (patients with unknown/missing maximum speech milestone in any of the timepoints of interest)
timeFrame: Baseline, 3, 6, and 12 months
measure: Number and proportion of patients with normal pulmonary evaluation during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients with at least 1 abnormal pulmonary evaluation during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced at least once chest abnormality symptoms during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced at least once pneumonia or respiratory illness during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who experienced at least once paradoxical breathing symptoms during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who used sitting and mobility support devices during the post-index period
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who used at least once the following sitting and mobility support devices during the post-index period: standing frame; positioning device; adaptive seating system; gait trainer; walker; wheelchair; scooter; other
timeFrame: Up to approximately 15 years
measure: Time from index date to the first initial improvement in motor function
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients who had overall improvement at the end of post-index period as per physicians' assessment for general impression, motor function, respiratory function, and swallow function
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients per survival status
timeFrame: Up to approximately 15 years
measure: Number and proportion of patients per cause of death
timeFrame: Up to approximately 15 years
Other outcomes:
Locations:
city: Bannockburn
country: United States
facility: Novartis
state: Illinois
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: