Trial Outcomes & Findings for A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy (NCT NCT03779334)

Last Updated: 2026-01-26

Results Overview

The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Gross Motor Scale is a commonly used measure of infant and toddler development (0 to 42 months). The normed-scores derived from the BSID-III are used in clinical practice to detect infants with developmental delays, as well as to evaluate developmental progress and the impact of therapeutic interventions. The gross motor scale consists of 72 items scored at 0 (unable to perform the activity) or 1 (criteria for item achieved). Item 22, "sits without support for 5 seconds", is not considered achieved if the infant sits alone for less than 5 seconds before losing balance and falling over, or if the infant uses his or her arms to prop him- or herself up. 90% CI for one sample binomial was computed using Clopper-Pearson (exact) method. An exact binomial test was performed. If the lower limit of the two-sided 90% CI was above the 5% threshold, the primary objective of the study was considered achieved.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

At Month 12

Results posted on

2026-01-26

Participant Flow

Overall, 26 infants with spinal muscular atrophy (SMA) were enrolled in the study across 7 different sites in 7 countries.

The study enrolled infants aged from birth to 6 weeks who were genetically diagnosed with SMA but were not yet presenting with symptoms. Study arms were based on the number of copies of the SMN2 gene.

Participant milestones

Participant milestones
Measure	3 SMN2 Copies, Risdiplam Infants with 3 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	>/=4 SMN2 Copies, Risdiplam Infants with 4 or more copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	2 SMN2 Copies, Risdiplam Infants with 2 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.
Overall Study STARTED	13	5	8
Overall Study Primary Efficacy Population	0	0	5
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	13	5	8

Reasons for withdrawal

Reasons for withdrawal
Measure	3 SMN2 Copies, Risdiplam Infants with 3 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	>/=4 SMN2 Copies, Risdiplam Infants with 4 or more copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	2 SMN2 Copies, Risdiplam Infants with 2 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.
Overall Study Withdrawal by Subject	0	0	3
Overall Study Ongoing in Study	13	5	5

Baseline Characteristics

A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	2 SMN2 Copies, Risdiplam n=8 Participants Infants with 2 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	3 SMN2 Copies, Risdiplam n=13 Participants Infants with 3 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	>/=4 SMN2 Copies, Risdiplam n=5 Participants Infants with 4 or more copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	Total n=26 Participants Total of all reporting groups
Age, Continuous	22.8 days STANDARD_DEVIATION 5.0 • n=25 Participants	28.9 days STANDARD_DEVIATION 7.5 • n=25 Participants	31.2 days STANDARD_DEVIATION 6.1 • n=50 Participants	27.5 days STANDARD_DEVIATION 7.1 • n=152 Participants
Sex: Female, Male Female	4 Participants n=25 Participants	9 Participants n=25 Participants	3 Participants n=50 Participants	16 Participants n=152 Participants
Sex: Female, Male Male	4 Participants n=25 Participants	4 Participants n=25 Participants	2 Participants n=50 Participants	10 Participants n=152 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants	3 Participants n=152 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=25 Participants	12 Participants n=25 Participants	5 Participants n=50 Participants	22 Participants n=152 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants	1 Participants n=25 Participants	0 Participants n=50 Participants	1 Participants n=152 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants	0 Participants n=152 Participants
Race (NIH/OMB) Asian	0 Participants n=25 Participants	1 Participants n=25 Participants	2 Participants n=50 Participants	3 Participants n=152 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants	0 Participants n=152 Participants
Race (NIH/OMB) Black or African American	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants	0 Participants n=152 Participants
Race (NIH/OMB) White	8 Participants n=25 Participants	11 Participants n=25 Participants	3 Participants n=50 Participants	22 Participants n=152 Participants
Race (NIH/OMB) More than one race	0 Participants n=25 Participants	0 Participants n=25 Participants	0 Participants n=50 Participants	0 Participants n=152 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants	1 Participants n=25 Participants	0 Participants n=50 Participants	1 Participants n=152 Participants

PRIMARY outcome

Timeframe: At Month 12

Population: Primary efficacy population included all infants in the intent-to-treat (ITT) population with two SMN2 copies (excluding the known SMN2 gene modifier mutation c.859G\>C) and a baseline compound muscle action potential (CMAP) amplitude \>/= 1.5 mV.

Outcome measures

Outcome measures
Measure	2 SMN2 Copies, Risdiplam n=5 Participants Infants with 2 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	3 SMN2 Copies, Risdiplam Infants with 3 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	>/=4 SMN2 Copies, Risdiplam Infants with 4 or more copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.
Percentage of Participants With Two Copies of the Survival Motor Neuron (SMN) 2 Gene (Excluding the Known SMN2 Gene Modifier Mutation c.859G>C) and Baseline Compound Muscle Action Potential (CMAP) >=1.5 Millivolt (mV) Who Are Sitting Without Support	80.0 percentage of participants Interval 34.26 to 98.98	—	—

SECONDARY outcome

Timeframe: At Month 12 and 24

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

HINE-2 assessment includes head control, sitting, voluntary grasp, ability to kick, rolling, crawling, standing, and walking

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population included all enrolled participants, regardless of whether they received risdiplam or not. Only participants with two copies of the SMN2 gene were included in this outcome measure.

Assessed in Item 22 of the BSID-III Gross Motor Scale. The BSID-III is a commonly used measure of infant and toddler development (0 to 42 months). The normed-scores derived from the BSID-III are used in clinical practice to detect infants with developmental delays, as well as to evaluate developmental progress and the impact of therapeutic interventions. The gross motor scale consists of 72 items scored at 0 (unable to perform the activity) or 1 (criteria for item achieved). Item 22, "sits without support for 5 seconds", is not considered achieved if the infant sits alone for less than 5 seconds before losing balance and falling over, or if the infant uses his or her arms to prop him- or herself up. 90% CI for one sample binomial was computed using Clopper-Pearson (exact) method.

Outcome measures

Outcome measures
Measure	2 SMN2 Copies, Risdiplam n=8 Participants Infants with 2 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	3 SMN2 Copies, Risdiplam Infants with 3 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	>/=4 SMN2 Copies, Risdiplam Infants with 4 or more copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.
Percentage of Participants With Two Copies of the SMN2 Gene Sitting Without Support for 5 Seconds (Independent of the CMAP Value at Baseline).	87.5 percentage of participants Interval 52.93 to 99.36	—	—

SECONDARY outcome

Timeframe: At Month 24

Assessed with BSID-III Gross Motor Scale

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

Assessed with BSID-III Gross Motor Scale

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 24

Assessed with BSID-III Gross Motor Scale

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 24

Assessed with BSID-III Gross Motor Scale

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 24 and 42

Assessed through BSID-III Gross Motor Scale

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: ITT population included all enrolled participants, regardless of whether they received risdiplam or not.

The CHOP-INTEND is a measure of motor function that was developed from the Test of Infant Motor Performance specifically for weak infants with neuromuscular disease. It consists of 16 items, where each item assesses a specific motor task (such as spontaneous movement of upper and lower extremity, hand grasping, rolling, head control, and others) graded on a scale of 0 to 4, where zero is no response and 4 is a complete response. A total score is calculated by summing the item scores (range 0 to 64) with lower scores indicating greater severity. A positive change from baseline indicates an improvement.

Outcome measures

Outcome measures
Measure	2 SMN2 Copies, Risdiplam n=8 Participants Infants with 2 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	3 SMN2 Copies, Risdiplam n=13 Participants Infants with 3 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	>/=4 SMN2 Copies, Risdiplam n=5 Participants Infants with 4 or more copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.
Change From Baseline Score in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale at Month 12 Baseline	46.50 score on a scale Interval 35.0 to 52.0	55.00 score on a scale Interval 44.0 to 62.0	50.00 score on a scale Interval 44.0 to 52.0
Change From Baseline Score in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale at Month 12 Change from Baseline at Month 12	9.50 score on a scale Interval -6.0 to 20.0	8.00 score on a scale Interval 2.0 to 20.0	16.00 score on a scale Interval 8.0 to 19.0

SECONDARY outcome

Timeframe: At Month 12

Population: ITT population included all enrolled participants, regardless of whether they received risdiplam or not.

The CHOP-INTEND is a measure of motor function that was developed from the Test of Infant Motor Performance specifically for weak infants with neuromuscular disease. It consists of 16 items, where each item assesses a specific motor task (such as spontaneous movement of upper and lower extremity, hand grasping, rolling, head control, and others) graded on a scale of 0 to 4, where zero is no response and 4 is a complete response. A total score is calculated by summing the item scores (range 0 to 64) with lower scores indicating greater severity. Data are presented with a two-sided 90% Clopper-Pearson (exact) CI for the proportion.

Outcome measures

Outcome measures
Measure	2 SMN2 Copies, Risdiplam n=8 Participants Infants with 2 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	3 SMN2 Copies, Risdiplam n=13 Participants Infants with 3 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	>/=4 SMN2 Copies, Risdiplam n=4 Participants Infants with 4 or more copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.
Percentage of Participants Who Achieve a Score of 40 or Higher, 50 or Higher, and 60 or Higher in the CHOP INTEND Motor Function Scale at Month 12 Score >=40	75.0 percentage of participants Interval 40.03 to 95.36	100 percentage of participants Interval 79.42 to 100.0	100 percentage of participants Interval 47.29 to 100.0
Percentage of Participants Who Achieve a Score of 40 or Higher, 50 or Higher, and 60 or Higher in the CHOP INTEND Motor Function Scale at Month 12 Score >=50	75.0 percentage of participants Interval 40.03 to 95.36	100 percentage of participants Interval 79.42 to 100.0	100 percentage of participants Interval 47.29 to 100.0
Percentage of Participants Who Achieve a Score of 40 or Higher, 50 or Higher, and 60 or Higher in the CHOP INTEND Motor Function Scale at Month 12 Score >=60	37.5 percentage of participants Interval 11.11 to 71.08	100 percentage of participants Interval 79.42 to 100.0	100 percentage of participants Interval 47.29 to 100.0

SECONDARY outcome

Timeframe: Up to Month 24

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12, 24, 36, 48 and 60

Based on the WHO Child Growth Standards (WHO 2019)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

Based on the WHO Child Growth Standards (WHO 2019)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12, 24, 36, 48 and 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12, 24, 36, 48 and 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Month 12 and 24

Measured by CMAP

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1, 56, 196, 364, 728 and at early withdrawal

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7 years

Adverse event severity is determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE) v5

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7 years

Outcome measures

Outcome data not reported

Adverse Events

2 SMN2 Copies, Risdiplam

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

3 SMN2 Copies, Risdiplam

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

>/=4 SMN2 Copies, Risdiplam

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	2 SMN2 Copies, Risdiplam n=8 participants at risk Infants with 2 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	3 SMN2 Copies, Risdiplam n=13 participants at risk Infants with 3 copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.	>/=4 SMN2 Copies, Risdiplam n=5 participants at risk Infants with 4 or more copies of SMN2 were enrolled to receive risdiplam orally once daily at a dose selected to achieve the targeted exposure range of close to 2000 ng\*hr/mL.
Gastrointestinal disorders Constipation	12.5% 1/8 • Number of events 1 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/13 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/5 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.
Infections and infestations Gastroenteritis	12.5% 1/8 • Number of events 1 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/13 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	20.0% 1/5 • Number of events 1 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.
Infections and infestations Urinary tract infection	0.00% 0/8 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/13 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	20.0% 1/5 • Number of events 2 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Femur fracture	12.5% 1/8 • Number of events 1 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/13 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/5 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.
Injury, poisoning and procedural complications Soft tissue injury	12.5% 1/8 • Number of events 1 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/13 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/5 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.
Pregnancy, puerperium and perinatal conditions Jaundice neonatal	12.5% 1/8 • Number of events 1 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/13 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.	0.00% 0/5 • From baseline up to the clinical cut off date (a minimum of 12 months and a maximum of 3.5 years) The safety population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER