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OpenTrials
Completed

NCT Number: 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

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.

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Key information

Conditions

Spinal Muscular Atrophy Central Nervous System Diseases Motor Neuron Disease Muscular Atrophy, Spinal Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Spinal Cord Diseases

Age range

Up to 5 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Novartis

Bannockburn, Illinois, 60015, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. Number and proportion of male patients

    Time frame: Baseline

  2. Number and proportion of female patients

    Time frame: Baseline

  3. Number and proportion of patients per race

    Time frame: Baseline

  4. Number and proportion of patients per insurance type

    Time frame: Baseline

  5. Number and proportion of patients per gestational age category at birth

    Time frame: Baseline

  6. Number and proportion of patients per country

    Time frame: Baseline

  7. Number and proportion of patients with prenatal screening performed and confirmed for SMA

    Time frame: Baseline

  8. Number and proportion of patients undergoing newborn screening for SMA

    Time frame: Baseline

  9. Number and proportion of patients experiencing SMA-related symptoms prior to initiation of the first DMT (index drug)

    Time frame: Baseline

  10. Mean age at onset of SMA-related symptoms experienced prior to initiation of the first DMT

    Time frame: Baseline

  11. Mean age at SMA genetic diagnosis

    Time frame: Baseline

  12. Number and proportion of patients who had as survival of motor neuron 1 (SMN1) genetic test

    Time frame: Baseline

  13. Number and proportion of patients per SMN1 genetic test result category

    Time frame: Baseline

  14. Number and proportion of patients who had a survival of motor neuron 2 (SMN2) genetic test

    Time frame: Baseline

  15. Number and proportion of patients per SMN2 gene copy number

    Time frame: Baseline

  16. Number and proportion of patients per SMA type at diagnosis

    Time frame: Baseline

  17. Mean body weight

    Time frame: Baseline

Secondary outcomes

  1. Time to first improvement from last pre-index/pre-switch assessment

    Time frame: Up to approximately 5 years

  2. Time from pre-index/last pre- switch until the last follow-up visit with available data for the overall developmental motor milestones rates

    Time frame: Up to approximately 5 years

  3. 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)

    Time frame: Up to approximately 5 years

    The HINE-2 assesses motor milestones and includes 8 categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. Overall scores can range from 0 to 26. Higher scores indicate higher levels of motor ability.

  4. Number and proportion of patients who achieved at least once ≥ 3 points increase on the Hammersmith Functional Motor Scale-Expanded (HFMSE)

    Time frame: Up to approximately 5 years

    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.

  5. Number and proportion of patients who achieved at least once ≥ 3 points decrease on the HFMSE

    Time frame: Up to approximately 5 years

    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.

  6. Number and proportion of patients who maintained score change ±3 points on the HFMSE

    Time frame: Up to approximately 5 years

    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.

  7. Change in score per month on the HFMSE

    Time frame: Baseline up to approximately 5 years

    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.

  8. Estimate of HFMSE score per timepoint during the post period, adjusted for the last pre-value

    Time frame: Up to approximately 15 years

    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.

  9. 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)

    Time frame: Up to approximately 5 years

    CHOP INTEND scores can range from 0 to 64, where 64 is the maximum possible score. A higher score indicates higher/better motor function.

  10. Number and proportion of patients who achieved at least once ≥4 points increase on the CHOP INTEND

    Time frame: Up to approximately 5 years

    CHOP INTEND scores can range from 0 to 64, where 64 is the maximum possible score. A higher score indicates higher/better motor function.

  11. Change in score per month on the CHOP INTEND

    Time frame: Baseline up to approximately 5 years

    CHOP INTEND scores can range from 0 to 64, where 64 is the maximum possible score. A higher score indicates higher/better motor function.

  12. Estimate of score per timepoint during the post period, adjusted for the last pre-value on the CHOP INTEND

    Time frame: Up to approximately 15 years

    CHOP INTEND scores can range from 0 to 64, where 64 is the maximum possible score. A higher score indicates higher/better motor function.

  13. Number and proportion of patients without any craniofacial deficits during the post-index period

    Time frame: Up to approximately 15 years

  14. 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

    Time frame: Up to approximately 15 years

  15. Number and proportion of patients who remained free of any non-oral support during the post-index period

    Time frame: Up to approximately 15 years

  16. Number and proportion of patients who did not remain free of any non-oral support during the post-index period

    Time frame: Up to approximately 15 years

  17. Number and proportion of patients who exhibited constipation at least once during the post-index period

    Time frame: Up to approximately 15 years

  18. Number and proportion of patients who exhibited failure to thrive or underweight at least once during the post-index period

    Time frame: Up to approximately 15 years

  19. Number and proportion of patients per the Pediatric-Functional Oral Intake Scale (p-FOIS) score at the timepoints of interest

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  20. Number and proportion of patients who had improvement (the p-FOIS score increased by at least 1 point between the timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  21. Number and proportion of patients who had decline (the p-FOIS score decreased by at least 1 point between the timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  22. Number and proportion of patients who maintained status (the p-FOIS score maintained stable between the timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  23. Number and proportion of patients with unknown status (unknown/missing p-FOIS score in any of the timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  24. Number and proportion of patients with p-FOIS <3 at the timepoints of interest in the functional swallow category

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  25. Number and proportion of patients with p-FOIS ≥ 3 at the timepoints of interest in the functional swallow category

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  26. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  27. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  28. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  29. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  30. Number and proportion of patients with unknown (unknown/missing p-FOIS score in any of the timepoints of interest) in the functional swallow category

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  31. Number and proportion of patients with p-FOIS <4 at the timepoints of interest in the total oral nutrition category

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  32. Number and proportion of patients with p-FOIS ≥ 4 at the timepoints of interest in the total oral nutrition category

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  33. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  34. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  35. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  36. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  37. 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

    Time frame: Baseline, 3, 6, and 12 months

    The p-FOIS score has a range of 1 (nothing taken orally) to 6 (age-appropriate oral intake).

  38. Number and proportion of patients without any swallow evaluation during the post-index period

    Time frame: Up to approximately 15 years

  39. Number and proportion of patients with at least 1 swallow evaluation during the post index period including the type of swallow evaluation

    Time frame: Up to approximately 15 years

  40. Number and proportion of patients with at least 1 symptom of interest related to eating during the post-index period

    Time frame: Up to approximately 15 years

    Symptoms of interest were coughing/choking with liquids; coughing/choking with solids; prolonged feeding times; fatigue with eating; swallowing or feeding difficulties; difficulty chewing; and wet/gurgles after eating.

  41. Number and proportion of patients without any sign of aspiration during the post-index period

    Time frame: Up to approximately 15 years

  42. 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

    Time frame: Up to approximately 15 years

  43. Number and proportion of patients without any deficits in swallowing during the post-index period

    Time frame: Up to approximately 15 years

  44. Number and proportion of patients who exhibited nasal regurgitation at least once during the post-index period

    Time frame: Up to approximately 15 years

  45. Number and proportion of patients who exhibited no swallow initiation at least once during the post-index period

    Time frame: Up to approximately 15 years

  46. Number and proportion of patients who exhibited pharyngeal residue at least once during the post-index period

    Time frame: Up to approximately 15 years

  47. Number and proportion of patients who exhibited aspiration at least once during the post-index period

    Time frame: Up to approximately 15 years

  48. Number and proportion of patients who suffered penetration at least once during the post-index period

    Time frame: Up to approximately 15 years

  49. Number and proportion of patients who were able to drink thin liquids during the post-index period

    Time frame: Up to approximately 15 years

  50. Number and proportion of patients who were able to drink thin nectar during the post-index period

    Time frame: Up to approximately 15 years

  51. Number and proportion of patients who were able to drink nectar during the post-index period

    Time frame: Up to approximately 15 years

  52. Number and proportion of patients who were able to drink honey during the post-index period

    Time frame: Up to approximately 15 years

  53. 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

    Time frame: Up to approximately 15 years

  54. Number and proportion of patients who did not experience fatigue with speech over the course of the day during the post-index period

    Time frame: Up to approximately 15 years

  55. Number and proportion of patients who experienced at least once fatigue with speech over the course of the day during the post-index period

    Time frame: Up to approximately 15 years

  56. Number and proportion of patients who experienced at least once clinical signs of aspiration during the post-index period

    Time frame: Up to approximately 15 years

  57. Number and proportion of patients who experienced at least once problem in chewing during the post-index period

    Time frame: Up to approximately 15 years

  58. Number and proportion of patients who experienced at least once aversion/disinterest in eating or drinking

    Time frame: Up to approximately 15 years

  59. Number and proportion of patients who experienced at least once a concern for insufficient oral nutrient ingestion

    Time frame: Up to approximately 15 years

  60. Number and proportion of patients per category of maximum speech milestone achieved during the post-index period.

    Time frame: Up to approximately 15 years

  61. Number and proportion of patients who experienced clinical signs of aspiration at the timepoints of interest

    Time frame: Baseline, 3, 6, and 12 months

  62. 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)

    Time frame: Baseline, 3, 6, and 12 months

  63. 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)

    Time frame: Baseline, 3, 6, and 12 months

  64. Number and proportion of patients who maintained status (patients without clinical signs of aspiration at both timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

  65. Number and proportion of patients who maintained status (patients with clinical signs of aspiration at both timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

  66. Number and proportion of patients with unknown status (patients with unknown/missing clinical signs of aspiration in any of the timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

  67. Number and proportion of patients who experienced fatigue with eating at the timepoints of interest

    Time frame: Baseline, 3, 6, and 12 months

  68. 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)

    Time frame: Baseline, 3, 6, and 12 months

  69. 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)

    Time frame: Baseline, 3, 6, and 12 months

  70. Number and proportion of patients who maintained status (patients who didn't experience fatigue with eating at both timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

  71. Number and proportion of patients who maintained status (patients who experienced fatigue with eating at both timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

  72. Number and proportion of patients with unknown status (patients with unknown/missing experience of fatigue with eating in any of the timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

  73. Number and proportion of patients per each category of maximum speech milestone achieved at the timepoints of interest

    Time frame: Baseline, 3, 6, and 12 months

  74. 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)

    Time frame: Baseline, 3, 6, and 12 months

  75. Number and proportion of patients with decline in speech milestones

    Time frame: Baseline, 3, 6, and 12 months

    Decline was defined as patients who had consonant and vowel combination; babbling word(s); combining 2 words together; speech understood by family members; or speech understood by unfamiliar listeners as a maximum speech milestone at the first timepoint of interest and cooing at the next timepoint of interest.

  76. 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)

    Time frame: Baseline, 3, 6, and 12 months

  77. Number and proportion of patients with unknown status (patients with unknown/missing maximum speech milestone in any of the timepoints of interest)

    Time frame: Baseline, 3, 6, and 12 months

  78. Number and proportion of patients with normal pulmonary evaluation during the post-index period

    Time frame: Up to approximately 15 years

  79. Number and proportion of patients with at least 1 abnormal pulmonary evaluation during the post-index period

    Time frame: Up to approximately 15 years

  80. Number and proportion of patients who experienced at least once chest abnormality symptoms during the post-index period

    Time frame: Up to approximately 15 years

  81. Number and proportion of patients who experienced at least once pneumonia or respiratory illness during the post-index period

    Time frame: Up to approximately 15 years

  82. Number and proportion of patients who experienced at least once paradoxical breathing symptoms during the post-index period

    Time frame: Up to approximately 15 years

  83. Number and proportion of patients who used sitting and mobility support devices during the post-index period

    Time frame: Up to approximately 15 years

  84. 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

    Time frame: Up to approximately 15 years

  85. Time from index date to the first initial improvement in motor function

    Time frame: Up to approximately 15 years

  86. 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

    Time frame: Up to approximately 15 years

  87. Number and proportion of patients per survival status

    Time frame: Up to approximately 15 years

  88. Number and proportion of patients per cause of death

    Time frame: Up to approximately 15 years

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Important dates

Study start
2022
Primary completion
2022
Study completion
2022
First posted
Dec 21, 2023
Registry last updated
Dec 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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