Spinal Muscular Atrophy
Conditions
Brief summary
This is a multi-center, exploratory, non-comparative, and open-label study to investigate the safety, tolerability, PK, and PK/PD relationship of risdiplam in adults, children and infants with Spinal Muscular Atrophy (SMA) previously enrolled in Study BP29420 (Moonfish) with the splicing modifier RO6885247 or previously treated with nusinersen, olesoxime or AVXS-101.
Interventions
DRUGRisdiplam
Risdiplam will be administered orally once daily.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 60 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of 5q-autosomal recessive SMA * Previous enrollment in Study BP29420 (Moonfish) with the splicing modifier RO6885247 or previous treatment with any of the following: 1.) Nusinersen (defined as having received \>= 4 doses of nusinersen, provided that the last dose was received \>= 90 days prior to screening) or 2.) Olesoxime (provided that the last dose was received \<= 12 months and \>= 90 days prior to screening) or 3.) AVXS-101 (provided that the time of treatment was \>= 12 months prior to screening) * Adequately recovered from any acute illness at the time of screening and considered well enough to participate in the opinion of the Investigator * For women of childbearing potential: negative blood pregnancy test at screening, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs for at least 28 days after the final dose of study drug * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm * For participants aged 2 years or younger at screening: 1.) Parent or caregiver of participant is willing to consider nasogastric, naso-jejunal or gastrostomy tube placement, as recommended by the Investigator, during the study to maintain safe hydration, nutrition and treatment delivery; 2.) Parent or caregiver of participant is willing to consider the use of non-invasive ventilation, as recommended by the Investigator during the study
Exclusion criteria
* Inability to meet study requirements * Concomitant participation in any investigational drug or device study * Previous participation in any investigational drug or device study within 90 days prior to screening, or 5 half-lives of the drug, whichever is longer with the exception of studies of olesoxime, AVXS-101, or nusinersen * Any history of gene or cell therapy, with the exception of AVXS-101 * Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator * Inadequate venous or capillary blood access for the study procedures, in the opinion of the Investigator * For patients aged \< 2 years, hospitalization for a pulmonary event within 2 months prior to screening and pulmonary function not fully recovered at the time of screening * Lactating women * Suspicion of regular consumption of drugs of abuse * For adults and adolescents only, positive urine test for drugs of abuse or alcohol at screening or Day -1 visit * Presence of clinically significant electrocardiogram (ECG) abnormalities before study drug administration from average of triplicate measurement or cardiovascular disease * History of malignancy if not considered cured * For participants aged \> 6 years, significant risk for suicidal behavior, in the opinion of the Investigator as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) * Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first dose administration * Recently initiated treatment for spinal muscular atrophy (within \<6 weeks prior to enrollment) with oral salbutamol or another beta 2-adrenergic agonist taken orally * Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or thioridazine, is not allowed * Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to risdiplam or to the constituents of its formulation * Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study * Recent history (less than one year) of ophthalmological diseases * Any prior use of an inhibitor or inducer of FMO1 or FMO3 taken within 2 weeks (or within 5 elimination half-lives, whichever is longer) prior to dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Trough Concentration (Ctrough) of Risdiplam | Predose at Year 5 visit | As pre-specified in the protocol, the PK data were not to be compared between participants who received different prior treatments (RO6885247, nusinersen, olesoxime and AVXS-101) received before entering this study, but to analyze the PK parameters of risdiplam. Hence, PK data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies. |
| Number of Participants With Adverse Events (AEs) | Baseline up to 5 years | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Number of Participants Who Discontinued Treatment Due to AEs | Baseline up to 5 years | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants who discontinued treatment due to AEs are reported here. |
| Number of Participants With Shift in Puberty Status From Baseline | Baseline, Week 52, 104, 156, 208 and 260 | Tanner staging of sexual development is a scale used to assess physical maturation as children transition through adolescence into adulthood. Scale defines physical development based on the following characteristics: pubic hair, penis, and testes development in boys; and pubic hair and breast development in girls. It consists of 5 stages, Stage I (prepubertal) to Stage V (mature adult). Participants under 9 years at screening began Tanner staging assessments at 1st visit following their 9th birthday. Tanner data are presented in three categories: Normal (expected stage of puberty based on participant's age at post-baseline visit), Delayed (pubertal development is behind expectations for age at post-baseline visit), & Missing (participant did not attend scheduled visit). Tanner staging assessments were scheduled for participants aged 9-17 years but were also conducted in some older participants, up to age 22. Shift in puberty status from baseline to each week has been represented here. |
| Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline up to Week 260 | Neurological examination was performed by asking questions to the participants and/or their caregiver, as well as observing the participants' behavior in general and while performing certain tasks. Questions and tasks were adapted to the age and motor ability of the participant. For very young participants, observing reaction to a sound, speech development, shifting attention to a newly introduced toy, observing the participant interact with the parent/caregiver & for older participants examination of social interaction (school, friends, activities, job as appropriate), memory (e.g., with short word recall), reasoning & language, drawing, etc. Participants with neurological conditions besides those expected with SMA and those expected with SMA are reported. |
| Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Up to approximately 5 years | C-SSRS was used to assess the lifetime suicidality of a participant (baseline) as well as any new instances of suicidality (since last visit). The interview prompts recollection of suicidal ideation (SI), including the intensity of the ideation, behavior and attempts with actual/potential lethality. A modified and reduced version (pediatric version) was used for children (aged 6-11 years). Categories have binary responses (yes/no) & include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active SI with Any Methods (Not Plan) without Intent to Act; Active SI with Some Intent to Act, without Specific Plan; Active SI with Specific Plan & Intent, Preparatory Acts & Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. SI or behavior is indicated by a yes answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates SI or behavior. |
| Anthropometric Examination: Change From Baseline in Weight | Baseline up to Week 260 | Weight was measured at baseline, Weeks 65, 91, and every 13 weeks thereafter for participants 2-17 years and at every visit for participants \<2 years. Per protocol, height was not measured at Day 7, Weeks 8, 17, 35, and thus not collected for all participants. No participants in the RO6885247 arm attended the Weeks 65, 169, 195, and 247 visit; none in the AVXS-101 arm attended the Week 247 visit. Symptom-directed height/weight assessments were done at clinically indicated visits as needed. |
| Anthropometric Examination: Change From Baseline in Height | Baseline up to Week 260 | Height of all participants able to stand was measured while standing using a stadiometer, with at least 3 independent measurements, which were averaged. Participants unable to stand during the measurement, height was derived from measurement of ulna length. For very young children, height was measured with child in a lying position using an inflexible length board with fixed headboard & movable footboard. Height was measured: baseline, Weeks 13,39,52,78 & 104 for participants 2-17 years; Weeks 52 & 104 for \>17 years & every visit for participants \<2 years. After Week 104, measurements occurred every 26 weeks. Per protocol, height was not measured at Weeks 2,4,17,26,35,43,61,65,87,91,96,117,143,169,195,221 &247 & thus not collected for all participants. No participants \<17 years in RO6885247, Olesoxime, or AVXS-101 arms attended the Week 260 visit & no participants in RO6885247 arm attended Week 39. Symptom-directed height assessments were done at clinically indicated visits as needed. |
| Anthropometric Examination: Change From Baseline in Head Circumference | Baseline up to Week 208 | Head circumference for participants aged \< 5 years was measured to the nearest 0.1 cm using a flexible, non-stretchable tape. Head circumference was measured around the widest part of the head from the most prominent point on the back of the head (occiput) to the most prominent part of the forehead between the eyebrows. The measurement was repeated three times, and the largest measurement was recorded. Head circumference was assessed for participants \< 5 years of age. Since all participants in the RO6885247 and Olesoxime arms were \> 5 years, data were not collected for these arms. Head circumference was not collected at Weeks 35 and 61 (AVXS-101 arm) and Weeks 87, 182, and 208 (Nusinersen arm) because the protocol only required this measurement for participants \< 5 years of age. At these timepoints, neither of the participants \< 5 years attended the visit, and other participants may have been \> 5 years of age. |
| Maximum Plasma Concentration (Cmax) of Risdiplam | Predose on Weeks 2, 4, 13, 26, 39, 52, 65, 91 and post-dose on Weeks 1, 4, 13, 52, 91 and 104 | As pre-specified in the protocol, the PK data were not to be compared between participants who received different prior treatments (RO6885247, nusinersen, olesoxime and AVXS-101) received before entering this study, but to analyze the PK parameters of risdiplam. Hence, PK data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies. |
| Area Under the Concentration-Time Curve (AUC0-24h) of Risdiplam | 24 hours Postdose at Year 2 Visit | As pre-specified in the protocol, the PK data were not to be compared between participants who received different prior treatments (RO6885247, nusinersen, olesoxime and AVXS-101) received before entering this study, but to analyze the PK parameters of risdiplam. Hence, PK data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival of Motor Neuron (SMN) Protein Levels in Blood | Baseline and Year 5 | SMA is caused by a homozygous deletion or mutation of the SMN 1 gene, which encodes SMN, an essential protein expressed in both neuronal and non-neuronal cells. In humans, there are two SMN genes, the SMN1 gene and its paralog SMN2. Risdiplam directly targets the underlying molecular deficiency of the disease and promotes the inclusion of exon 7 to generate full-length SMN2 mRNA, which therefore increases the production of functional SMN protein. As pre-specified in the protocol, the PD data were not to be compared between participants who received different prior treatments, but to analyze the PD parameters of risdiplam. Hence, PD data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies. |
Countries
Belgium, France, Germany, Italy, Netherlands, Poland, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
A total of 174 adult and pediatric participants with spinal muscular atrophy (SMA) took part in the study at 24 investigative sites across 9 countries from 03 March 2017 to 07 February 2025.
Pre-assignment details
This study included a 2-year treatment period followed by a 3-year open-label extension (OLE) period. Participants previously enrolled in Study BP29420 (NCT02240355) (Moonfish) and treated with the splicing modifier RO6885247 or previously treated with nusinersen, onasemnogene abeparvovec (AVXS-101), or olesoxime, were enrolled to receive risdiplam. 1 participant previously treated with 'Olesoxime' discontinued per physician's decision before receiving any treatment.
Participants by arm
| Arm | Count |
|---|---|
| RO6885247 Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years. | 13 |
| Nusinersen Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years. | 76 |
| Olesoxime Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years. | 71 |
| AVXS-101 Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years. | 14 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Open-label Extension Period | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Open-label Extension Period | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Open-label Extension Period | Reason Not Specified | 0 | 0 | 0 | 0 | 0 | 5 | 3 | 0 |
| Open-label Extension Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 7 | 11 | 4 |
| Treatment Period | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Discontinued, but Recorded as Completed Open-label Treatment by the Investigator | 0 | 1 | 2 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Non-compliance With Study Drug | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Physician Decision | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Reason Not Specified | 0 | 4 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 2 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | RO6885247 | Nusinersen | Olesoxime | AVXS-101 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32.3 years STANDARD_DEVIATION 14.2 | 16.1 years STANDARD_DEVIATION 13.5 | 18.5 years STANDARD_DEVIATION 5.7 | 2.5 years STANDARD_DEVIATION 1.2 | 17.2 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 6 Participants | 3 Participants | 3 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 66 Participants | 63 Participants | 11 Participants | 153 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 5 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 8 Participants | 12 Participants | 0 Participants | 20 Participants |
| Race (NIH/OMB) White | 11 Participants | 66 Participants | 56 Participants | 10 Participants | 143 Participants |
| Sex: Female, Male Female | 4 Participants | 36 Participants | 36 Participants | 3 Participants | 79 Participants |
| Sex: Female, Male Male | 9 Participants | 40 Participants | 35 Participants | 11 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 76 | 0 / 70 | 2 / 14 |
| other Total, other adverse events | 12 / 13 | 76 / 76 | 69 / 70 | 14 / 14 |
| serious Total, serious adverse events | 3 / 13 | 25 / 76 | 24 / 70 | 8 / 14 |
Outcome results
Primary
Anthropometric Examination: Change From Baseline in Head Circumference
Head circumference for participants aged \< 5 years was measured to the nearest 0.1 cm using a flexible, non-stretchable tape. Head circumference was measured around the widest part of the head from the most prominent point on the back of the head (occiput) to the most prominent part of the forehead between the eyebrows. The measurement was repeated three times, and the largest measurement was recorded. Head circumference was assessed for participants \< 5 years of age. Since all participants in the RO6885247 and Olesoxime arms were \> 5 years, data were not collected for these arms. Head circumference was not collected at Weeks 35 and 61 (AVXS-101 arm) and Weeks 87, 182, and 208 (Nusinersen arm) because the protocol only required this measurement for participants \< 5 years of age. At these timepoints, neither of the participants \< 5 years attended the visit, and other participants may have been \> 5 years of age.
Time frame: Baseline up to Week 208
Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 4 | 0.27 cm | Standard Deviation 1.55 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 61 | 1.50 cm | — |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 104 | 1.60 cm | Standard Deviation 0.14 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 13 | 0.70 cm | Standard Deviation 1.54 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 26 | 1.30 cm | Standard Deviation 0.77 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 35 | 0.00 cm | — |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 39 | 1.90 cm | Standard Deviation 1.15 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 52 | 1.90 cm | Standard Deviation 1.15 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 65 | 2.75 cm | Standard Deviation 1.77 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 78 | 2.40 cm | Standard Deviation 1.44 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 91 | 1.50 cm | — |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 130 | 5.50 cm | — |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 156 | 3.00 cm | — |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Baseline | 51.10 cm | Standard Deviation 3.43 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Head Circumference | Week 2 | 0.28 cm | Standard Deviation 0.85 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 182 | 3.50 cm | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 78 | 1.58 cm | Standard Deviation 0.75 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 87 | 0.50 cm | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 208 | 3.50 cm | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 4 | 0.17 cm | Standard Deviation 0.51 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 91 | 1.05 cm | Standard Deviation 2.05 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 13 | 0.51 cm | Standard Deviation 0.51 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 104 | 1.70 cm | Standard Deviation 0.77 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 26 | 0.58 cm | Standard Deviation 1.02 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 2 | 0.26 cm | Standard Deviation 0.43 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 130 | 2.10 cm | Standard Deviation 1.52 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 39 | 0.42 cm | Standard Deviation 0.99 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Baseline | 50.61 cm | Standard Deviation 2.15 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 52 | 1.34 cm | Standard Deviation 0.91 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 156 | 3.00 cm | Standard Deviation 0.71 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Head Circumference | Week 65 | 1.67 cm | Standard Deviation 1.89 |
Primary
Anthropometric Examination: Change From Baseline in Height
Height of all participants able to stand was measured while standing using a stadiometer, with at least 3 independent measurements, which were averaged. Participants unable to stand during the measurement, height was derived from measurement of ulna length. For very young children, height was measured with child in a lying position using an inflexible length board with fixed headboard & movable footboard. Height was measured: baseline, Weeks 13,39,52,78 & 104 for participants 2-17 years; Weeks 52 & 104 for \>17 years & every visit for participants \<2 years. After Week 104, measurements occurred every 26 weeks. Per protocol, height was not measured at Weeks 2,4,17,26,35,43,61,65,87,91,96,117,143,169,195,221 &247 & thus not collected for all participants. No participants \<17 years in RO6885247, Olesoxime, or AVXS-101 arms attended the Week 260 visit & no participants in RO6885247 arm attended Week 39. Symptom-directed height assessments were done at clinically indicated visits as needed.
Time frame: Baseline up to Week 260
Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 208 | -2.28 centimeters (cm) | Standard Deviation 5.52 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 52 | -0.38 centimeters (cm) | Standard Deviation 2.98 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 104 | -0.87 centimeters (cm) | Standard Deviation 1.92 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 156 | -0.20 centimeters (cm) | Standard Deviation 0.45 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 221 | 0.00 centimeters (cm) | — |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 61 | 0.00 centimeters (cm) | — |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 35 | -0.40 centimeters (cm) | Standard Deviation 3.75 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Baseline | 171.36 centimeters (cm) | Standard Deviation 8.36 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 130 | -1.60 centimeters (cm) | Standard Deviation 2.13 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 13 | -0.20 centimeters (cm) | Standard Deviation 1.71 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 182 | -2.25 centimeters (cm) | Standard Deviation 5.54 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 78 | -0.71 centimeters (cm) | Standard Deviation 2.16 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 234 | -1.04 centimeters (cm) | Standard Deviation 5.25 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 17 | -0.84 centimeters (cm) | Standard Deviation 3.56 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Height | Week 143 | 0.00 centimeters (cm) | — |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 52 | 6.14 centimeters (cm) | Standard Deviation 5.31 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 260 | 29.00 centimeters (cm) | Standard Deviation 5.66 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 182 | 15.36 centimeters (cm) | Standard Deviation 11.34 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 61 | 11.41 centimeters (cm) | Standard Deviation 9.06 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 2 | 0.00 centimeters (cm) | Standard Deviation 0 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 65 | 9.80 centimeters (cm) | Standard Deviation 6.91 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 247 | 10.18 centimeters (cm) | Standard Deviation 14.39 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 78 | 9.92 centimeters (cm) | Standard Deviation 6.32 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 4 | 1.00 centimeters (cm) | Standard Deviation 1.41 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 234 | 17.18 centimeters (cm) | Standard Deviation 13.14 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 169 | 13.46 centimeters (cm) | Standard Deviation 12.09 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 156 | 12.90 centimeters (cm) | Standard Deviation 10.31 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 91 | 17.00 centimeters (cm) | Standard Deviation 7.07 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 104 | 11.33 centimeters (cm) | Standard Deviation 7.14 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 13 | 1.08 centimeters (cm) | Standard Deviation 4.1 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 143 | 5.91 centimeters (cm) | Standard Deviation 6.39 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 117 | 9.20 centimeters (cm) | Standard Deviation 6.11 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 130 | 12.15 centimeters (cm) | Standard Deviation 8.73 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 17 | -10.99 centimeters (cm) | Standard Deviation 28.36 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 26 | 6.50 centimeters (cm) | Standard Deviation 6.36 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 35 | 2.92 centimeters (cm) | Standard Deviation 3.38 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Baseline | 141.21 centimeters (cm) | Standard Deviation 26.17 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 39 | 4.81 centimeters (cm) | Standard Deviation 4.13 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 208 | 16.13 centimeters (cm) | Standard Deviation 11.69 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Height | Week 43 | 11.41 centimeters (cm) | Standard Deviation 7.59 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 117 | 4.86 centimeters (cm) | Standard Deviation 3.15 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Baseline | 161.71 centimeters (cm) | Standard Deviation 13.86 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 13 | 1.23 centimeters (cm) | Standard Deviation 5.09 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 35 | 0.05 centimeters (cm) | Standard Deviation 1.25 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 43 | 3.55 centimeters (cm) | Standard Deviation 5.01 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 52 | 2.36 centimeters (cm) | Standard Deviation 5.66 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 61 | 4.61 centimeters (cm) | Standard Deviation 6.33 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 65 | 0.88 centimeters (cm) | Standard Deviation 0.76 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 78 | 3.90 centimeters (cm) | Standard Deviation 6.8 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 87 | 4.77 centimeters (cm) | Standard Deviation 3.05 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 96 | 6.96 centimeters (cm) | Standard Deviation 14.28 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 104 | 5.14 centimeters (cm) | Standard Deviation 7.33 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 39 | 6.18 centimeters (cm) | Standard Deviation 9.33 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 130 | 4.70 centimeters (cm) | Standard Deviation 7.8 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 143 | 5.00 centimeters (cm) | — |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 156 | 4.43 centimeters (cm) | Standard Deviation 6.8 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 169 | 0.00 centimeters (cm) | — |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 182 | 4.67 centimeters (cm) | Standard Deviation 6.31 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 208 | 4.91 centimeters (cm) | Standard Deviation 8.6 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 221 | 9.77 centimeters (cm) | — |
| Olesoxime | Anthropometric Examination: Change From Baseline in Height | Week 234 | 4.95 centimeters (cm) | Standard Deviation 7.88 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 78 | 9.09 centimeters (cm) | Standard Deviation 4.04 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 4 | 0.33 centimeters (cm) | Standard Deviation 0.58 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 65 | 8.00 centimeters (cm) | Standard Deviation 1.73 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 52 | 6.83 centimeters (cm) | Standard Deviation 3.01 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Baseline | 92.37 centimeters (cm) | Standard Deviation 11.23 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 182 | 21.54 centimeters (cm) | Standard Deviation 2.76 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 195 | 31.74 centimeters (cm) | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 43 | 7.00 centimeters (cm) | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 39 | 2.41 centimeters (cm) | Standard Deviation 3.25 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 234 | 28.21 centimeters (cm) | Standard Deviation 5.49 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 208 | 26.17 centimeters (cm) | Standard Deviation 6.55 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 26 | 0.00 centimeters (cm) | Standard Deviation 1.41 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 130 | 16.11 centimeters (cm) | Standard Deviation 5.48 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 104 | 14.54 centimeters (cm) | Standard Deviation 3.95 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 2 | 0.00 centimeters (cm) | Standard Deviation 0 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 91 | 10.00 centimeters (cm) | Standard Deviation 4.24 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 87 | 5.78 centimeters (cm) | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 13 | 2.78 centimeters (cm) | Standard Deviation 2.14 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Height | Week 156 | 22.02 centimeters (cm) | Standard Deviation 4.97 |
Primary
Anthropometric Examination: Change From Baseline in Weight
Weight was measured at baseline, Weeks 65, 91, and every 13 weeks thereafter for participants 2-17 years and at every visit for participants \<2 years. Per protocol, height was not measured at Day 7, Weeks 8, 17, 35, and thus not collected for all participants. No participants in the RO6885247 arm attended the Weeks 65, 169, 195, and 247 visit; none in the AVXS-101 arm attended the Week 247 visit. Symptom-directed height/weight assessments were done at clinically indicated visits as needed.
Time frame: Baseline up to Week 260
Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 4 | -0.89 kilograms (kg) | Standard Deviation 3.15 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 91 | -0.85 kilograms (kg) | Standard Deviation 3.68 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 87 | 2.15 kilograms (kg) | — |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 35 | -1.51 kilograms (kg) | Standard Deviation 4.21 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 221 | 1.35 kilograms (kg) | Standard Deviation 0.49 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 78 | -0.19 kilograms (kg) | Standard Deviation 3.81 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 39 | -0.20 kilograms (kg) | Standard Deviation 2.55 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 156 | 0.28 kilograms (kg) | Standard Deviation 4.66 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 70 | -1.72 kilograms (kg) | Standard Deviation 4.27 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 43 | -1.09 kilograms (kg) | Standard Deviation 4.17 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 143 | 2.90 kilograms (kg) | — |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 61 | 6.40 kilograms (kg) | — |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 52 | -0.26 kilograms (kg) | Standard Deviation 3.32 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Day 7 | 0.09 kilograms (kg) | Standard Deviation 0.2 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 260 | 2.81 kilograms (kg) | Standard Deviation 3.49 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 2 | -2.79 kilograms (kg) | Standard Deviation 10.66 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 8 | -0.17 kilograms (kg) | Standard Deviation 2.38 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 130 | -0.60 kilograms (kg) | Standard Deviation 3.56 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 234 | 1.56 kilograms (kg) | Standard Deviation 2.65 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 117 | -0.10 kilograms (kg) | — |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 208 | 0.51 kilograms (kg) | Standard Deviation 2.68 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 13 | 0.45 kilograms (kg) | Standard Deviation 1.91 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 182 | 1.94 kilograms (kg) | Standard Deviation 4.09 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 104 | 0.45 kilograms (kg) | Standard Deviation 4.5 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 96 | 9.60 kilograms (kg) | — |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 17 | -0.33 kilograms (kg) | Standard Deviation 2.91 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Baseline | 59.19 kilograms (kg) | Standard Deviation 20.47 |
| RO6885247 | Anthropometric Examination: Change From Baseline in Weight | Week 26 | -1.26 kilograms (kg) | Standard Deviation 3.99 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 26 | 1.25 kilograms (kg) | Standard Deviation 2.01 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 61 | 2.07 kilograms (kg) | Standard Deviation 1.7 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 70 | -0.93 kilograms (kg) | Standard Deviation 3.97 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Baseline | 39.29 kilograms (kg) | Standard Deviation 22.3 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Day 7 | 0.13 kilograms (kg) | Standard Deviation 0.31 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 2 | 0.15 kilograms (kg) | Standard Deviation 0.8 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 4 | 0.29 kilograms (kg) | Standard Deviation 0.91 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 8 | 0.00 kilograms (kg) | Standard Deviation 0.17 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 13 | 0.64 kilograms (kg) | Standard Deviation 1.57 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 17 | 2.07 kilograms (kg) | Standard Deviation 3.09 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 35 | 2.12 kilograms (kg) | Standard Deviation 1.69 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 39 | 1.06 kilograms (kg) | Standard Deviation 2.96 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 43 | 2.95 kilograms (kg) | Standard Deviation 3.92 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 52 | 1.93 kilograms (kg) | Standard Deviation 3.84 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 65 | 2.96 kilograms (kg) | Standard Deviation 3.14 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 78 | 3.42 kilograms (kg) | Standard Deviation 3.84 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 87 | 2.80 kilograms (kg) | Standard Deviation 4.67 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 91 | 4.33 kilograms (kg) | Standard Deviation 4.75 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 96 | 3.52 kilograms (kg) | Standard Deviation 3.12 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 104 | 3.96 kilograms (kg) | Standard Deviation 5.33 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 117 | 4.30 kilograms (kg) | Standard Deviation 3.1 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 130 | 5.30 kilograms (kg) | Standard Deviation 6.07 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 143 | 2.69 kilograms (kg) | Standard Deviation 4.04 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 156 | 6.44 kilograms (kg) | Standard Deviation 6.39 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 169 | 3.29 kilograms (kg) | Standard Deviation 5.49 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 182 | 7.37 kilograms (kg) | Standard Deviation 6.96 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 195 | 22.00 kilograms (kg) | — |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 208 | 8.70 kilograms (kg) | Standard Deviation 7.71 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 221 | 7.70 kilograms (kg) | — |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 234 | 9.26 kilograms (kg) | Standard Deviation 7.91 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 247 | 4.73 kilograms (kg) | Standard Deviation 4.89 |
| Nusinersen | Anthropometric Examination: Change From Baseline in Weight | Week 260 | 10.03 kilograms (kg) | Standard Deviation 8.41 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 247 | 11.10 kilograms (kg) | — |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 260 | 7.41 kilograms (kg) | Standard Deviation 9.11 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 91 | 2.11 kilograms (kg) | Standard Deviation 4.99 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 208 | 4.82 kilograms (kg) | Standard Deviation 8.37 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 96 | 3.19 kilograms (kg) | Standard Deviation 4.98 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 13 | 0.63 kilograms (kg) | Standard Deviation 2.28 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 104 | 3.21 kilograms (kg) | Standard Deviation 5.02 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 117 | 3.45 kilograms (kg) | Standard Deviation 3.24 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 4 | 0.37 kilograms (kg) | Standard Deviation 1.86 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 130 | 2.95 kilograms (kg) | Standard Deviation 5.51 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 221 | 3.50 kilograms (kg) | — |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 143 | 4.35 kilograms (kg) | Standard Deviation 4.9 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Baseline | 46.48 kilograms (kg) | Standard Deviation 15.57 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 156 | 3.81 kilograms (kg) | Standard Deviation 6.45 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 169 | 8.90 kilograms (kg) | Standard Deviation 4.38 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 2 | 0.19 kilograms (kg) | Standard Deviation 1.73 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 234 | 6.29 kilograms (kg) | Standard Deviation 8.55 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 182 | 4.27 kilograms (kg) | Standard Deviation 7.81 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 52 | 1.35 kilograms (kg) | Standard Deviation 3.39 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 43 | 1.56 kilograms (kg) | Standard Deviation 5.29 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 61 | 0.25 kilograms (kg) | Standard Deviation 1.46 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 195 | 7.50 kilograms (kg) | — |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 65 | 1.96 kilograms (kg) | Standard Deviation 3.87 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 39 | 0.99 kilograms (kg) | Standard Deviation 2.68 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 70 | -1.38 kilograms (kg) | Standard Deviation 3.6 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 35 | -0.10 kilograms (kg) | Standard Deviation 3.36 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 78 | 1.77 kilograms (kg) | Standard Deviation 4.31 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 87 | 3.91 kilograms (kg) | Standard Deviation 4.37 |
| Olesoxime | Anthropometric Examination: Change From Baseline in Weight | Week 26 | 1.14 kilograms (kg) | Standard Deviation 4.03 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 87 | 5.30 kilograms (kg) | Standard Deviation 5.8 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 195 | 5.20 kilograms (kg) | Standard Deviation 0.99 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 156 | 4.02 kilograms (kg) | Standard Deviation 2.1 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 260 | 9.54 kilograms (kg) | Standard Deviation 6.23 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 91 | 2.07 kilograms (kg) | Standard Deviation 0.92 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 13 | 0.07 kilograms (kg) | Standard Deviation 0.46 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 26 | 0.52 kilograms (kg) | Standard Deviation 0.68 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 169 | 2.10 kilograms (kg) | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 96 | 0.70 kilograms (kg) | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 61 | 1.30 kilograms (kg) | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 208 | 5.44 kilograms (kg) | Standard Deviation 3.33 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 70 | 1.30 kilograms (kg) | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 104 | 3.08 kilograms (kg) | Standard Deviation 3.18 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 4 | 0.03 kilograms (kg) | Standard Deviation 0.37 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 39 | 0.90 kilograms (kg) | Standard Deviation 1.02 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 78 | 2.61 kilograms (kg) | Standard Deviation 2.37 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 117 | 1.86 kilograms (kg) | Standard Deviation 0.84 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 2 | 0.00 kilograms (kg) | Standard Deviation 0.32 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 182 | 4.97 kilograms (kg) | Standard Deviation 2.41 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 43 | 4.75 kilograms (kg) | Standard Deviation 3.32 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 130 | 3.19 kilograms (kg) | Standard Deviation 1.49 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Baseline | 12.87 kilograms (kg) | Standard Deviation 3.35 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 234 | 7.77 kilograms (kg) | Standard Deviation 5.04 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 65 | 2.54 kilograms (kg) | Standard Deviation 2.4 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 143 | 1.70 kilograms (kg) | — |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 52 | 1.71 kilograms (kg) | Standard Deviation 2.13 |
| AVXS-101 | Anthropometric Examination: Change From Baseline in Weight | Week 221 | 3.80 kilograms (kg) | — |
Primary
Area Under the Concentration-Time Curve (AUC0-24h) of Risdiplam
As pre-specified in the protocol, the PK data were not to be compared between participants who received different prior treatments (RO6885247, nusinersen, olesoxime and AVXS-101) received before entering this study, but to analyze the PK parameters of risdiplam. Hence, PK data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies.
Time frame: 24 hours Postdose at Year 2 Visit
Population: PK population included all participants with at least one timepoint with a measurable drug concentration. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RO6885247 | Area Under the Concentration-Time Curve (AUC0-24h) of Risdiplam | 1720 nanograms*hour/milliliter (ng*h/mL) |
Primary
Maximum Plasma Concentration (Cmax) of Risdiplam
As pre-specified in the protocol, the PK data were not to be compared between participants who received different prior treatments (RO6885247, nusinersen, olesoxime and AVXS-101) received before entering this study, but to analyze the PK parameters of risdiplam. Hence, PK data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies.
Time frame: Predose on Weeks 2, 4, 13, 26, 39, 52, 65, 91 and post-dose on Weeks 1, 4, 13, 52, 91 and 104
Population: PK population included all participants with at least one timepoint with a measurable drug concentration. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RO6885247 | Maximum Plasma Concentration (Cmax) of Risdiplam | 120 nanograms per milliliter (ng/mL) |
Primary
Number of Participants Who Discontinued Treatment Due to AEs
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants who discontinued treatment due to AEs are reported here.
Time frame: Baseline up to 5 years
Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RO6885247 | Number of Participants Who Discontinued Treatment Due to AEs | 0 Participants |
| Nusinersen | Number of Participants Who Discontinued Treatment Due to AEs | 1 Participants |
| Olesoxime | Number of Participants Who Discontinued Treatment Due to AEs | 0 Participants |
| AVXS-101 | Number of Participants Who Discontinued Treatment Due to AEs | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Baseline up to 5 years
Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RO6885247 | Number of Participants With Adverse Events (AEs) | 12 Participants |
| Nusinersen | Number of Participants With Adverse Events (AEs) | 76 Participants |
| Olesoxime | Number of Participants With Adverse Events (AEs) | 70 Participants |
| AVXS-101 | Number of Participants With Adverse Events (AEs) | 14 Participants |
Primary
Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
C-SSRS was used to assess the lifetime suicidality of a participant (baseline) as well as any new instances of suicidality (since last visit). The interview prompts recollection of suicidal ideation (SI), including the intensity of the ideation, behavior and attempts with actual/potential lethality. A modified and reduced version (pediatric version) was used for children (aged 6-11 years). Categories have binary responses (yes/no) & include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active SI with Any Methods (Not Plan) without Intent to Act; Active SI with Some Intent to Act, without Specific Plan; Active SI with Specific Plan & Intent, Preparatory Acts & Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. SI or behavior is indicated by a yes answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates SI or behavior.
Time frame: Up to approximately 5 years
Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Participants with SI, suicidal behavior, and self-injurious behavior without suicidal intent are reported for this outcome measure. Overall number analyzed are the number of participants with at least one post-baseline assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RO6885247 | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior Without Suicidal Intent | 0 Participants |
| RO6885247 | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 1 Participants |
| RO6885247 | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behaviour | 0 Participants |
| Nusinersen | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 5 Participants |
| Nusinersen | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior Without Suicidal Intent | 0 Participants |
| Nusinersen | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behaviour | 0 Participants |
| Olesoxime | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behaviour | 0 Participants |
| Olesoxime | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 2 Participants |
| Olesoxime | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior Without Suicidal Intent | 1 Participants |
| AVXS-101 | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| AVXS-101 | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior Without Suicidal Intent | 0 Participants |
| AVXS-101 | Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behaviour | 0 Participants |
Primary
Number of Participants With Protocol-defined Neurological Conditions (NC)
Neurological examination was performed by asking questions to the participants and/or their caregiver, as well as observing the participants' behavior in general and while performing certain tasks. Questions and tasks were adapted to the age and motor ability of the participant. For very young participants, observing reaction to a sound, speech development, shifting attention to a newly introduced toy, observing the participant interact with the parent/caregiver & for older participants examination of social interaction (school, friends, activities, job as appropriate), memory (e.g., with short word recall), reasoning & language, drawing, etc. Participants with neurological conditions besides those expected with SMA and those expected with SMA are reported.
Time frame: Baseline up to Week 260
Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 234: NC Expected With SMA | 10 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 78: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 2: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 130: NC Expected With SMA | 10 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 78: NC Expected With SMA | 11 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 260: NC Expected With SMA | 10 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 87: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 130: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 87: NC Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 2: NC Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 91: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 91: NC Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 182: NC Expected With SMA | 9 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 104: NC Expected With SMA | 11 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 104: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 4: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 234: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 208: NC Expected With SMA | 7 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 4: NC Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 65: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 13: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 208: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 13: NC Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 260: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 26: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 26: NC Expected With SMA | 10 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 182: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 39: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 39: NC Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 169: NC Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 52: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 52: NC Expected With SMA | 11 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline: NC Expected With SMA | 13 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 169: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 61: NC Besides Those Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 156: NC Expected With SMA | 7 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 61: NC Expected With SMA | 0 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 156: NC Besides Those Expected With SMA | 1 Participants |
| RO6885247 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 65: NC Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 234: NC Expected With SMA | 53 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 130: NC Expected With SMA | 63 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 13: NC Expected With SMA | 2 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 78: NC Besides Those Expected With SMA | 1 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 169: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 182: NC Expected With SMA | 52 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 61: NC Expected With SMA | 1 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 78: NC Expected With SMA | 58 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 26: NC Besides Those Expected With SMA | 1 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 130: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 2: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 87: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 234: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 182: NC Besides Those Expected With SMA | 3 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 52: NC Expected With SMA | 65 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 87: NC Expected With SMA | 1 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 26: NC Expected With SMA | 52 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 104: NC Expected With SMA | 64 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline: NC Expected With SMA | 75 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 91: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 2: NC Expected With SMA | 3 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 156: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 91: NC Expected With SMA | 2 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 65: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 39: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline: NC Besides Those Expected With SMA | 1 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 104: NC Besides Those Expected With SMA | 1 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 208: NC Expected With SMA | 52 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 169: NC Expected With SMA | 1 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 4: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 61: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 39: NC Expected With SMA | 1 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 260: NC Expected With SMA | 52 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 4: NC Expected With SMA | 3 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 156: NC Expected With SMA | 62 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 208: NC Besides Those Expected With SMA | 2 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 65: NC Expected With SMA | 2 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 13: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 260: NC Besides Those Expected With SMA | 0 Participants |
| Nusinersen | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 52: NC Besides Those Expected With SMA | 1 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 260: NC Expected With SMA | 49 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 104: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 104: NC Expected With SMA | 63 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 234: NC Expected With SMA | 50 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline: NC Expected With SMA | 70 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 2: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 2: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 4: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 4: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 13: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 13: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 26: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 26: NC Expected With SMA | 45 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 39: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 39: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 52: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 52: NC Expected With SMA | 61 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 61: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 65: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 65: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 78: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 78: NC Expected With SMA | 63 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 87: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 87: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 91: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 91: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 130: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 130: NC Expected With SMA | 60 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 156: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 156: NC Expected With SMA | 57 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 169: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 169: NC Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 182: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 182: NC Expected With SMA | 55 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 208: NC Besides Those Expected With SMA | 1 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 208: NC Expected With SMA | 51 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 234: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 260: NC Besides Those Expected With SMA | 0 Participants |
| Olesoxime | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 61: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 61: NC Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 182: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 156: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 61: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 234: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 156: NC Expected With SMA | 12 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 52: NC Expected With SMA | 10 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 52: NC Besides Those Expected With SMA | 2 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline: NC Expected With SMA | 13 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 169: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 39: NC Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 39: NC Besides Those Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Baseline: NC Besides Those Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 169: NC Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 26: NC Expected With SMA | 4 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 26: NC Besides Those Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 260: NC Expected With SMA | 7 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 13: NC Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 234: NC Expected With SMA | 9 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 182: NC Expected With SMA | 9 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 13: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 4: NC Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 91: NC Besides Those Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 208: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 4: NC Besides Those Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 2: NC Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 260: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 104: NC Besides Those Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 91: NC Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 87: NC Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 104: NC Expected With SMA | 12 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 87: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 78: NC Expected With SMA | 12 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 208: NC Expected With SMA | 10 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 130: NC Besides Those Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 78: NC Besides Those Expected With SMA | 2 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 65: NC Expected With SMA | 1 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 2: NC Besides Those Expected With SMA | 0 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 130: NC Expected With SMA | 12 Participants |
| AVXS-101 | Number of Participants With Protocol-defined Neurological Conditions (NC) | Week 65: NC Besides Those Expected With SMA | 0 Participants |
Primary
Number of Participants With Shift in Puberty Status From Baseline
Tanner staging of sexual development is a scale used to assess physical maturation as children transition through adolescence into adulthood. Scale defines physical development based on the following characteristics: pubic hair, penis, and testes development in boys; and pubic hair and breast development in girls. It consists of 5 stages, Stage I (prepubertal) to Stage V (mature adult). Participants under 9 years at screening began Tanner staging assessments at 1st visit following their 9th birthday. Tanner data are presented in three categories: Normal (expected stage of puberty based on participant's age at post-baseline visit), Delayed (pubertal development is behind expectations for age at post-baseline visit), & Missing (participant did not attend scheduled visit). Tanner staging assessments were scheduled for participants aged 9-17 years but were also conducted in some older participants, up to age 22. Shift in puberty status from baseline to each week has been represented here.
Time frame: Baseline, Week 52, 104, 156, 208 and 260
Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Overall number analyzed is the number of participants with data available for analysis. No participants from the AVXS-101 arm were assessed for Tanner staging since all participants in this arm were under 9 years of age.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 260 Status Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 156 Status Missing | 4 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 104 Status Missing | 4 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 52 Status Normal | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 156 Status Normal | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 104 Status Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 208 Status Missing | 4 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 104 Status Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 260 Status Missing | 4 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 52 Status Missing | 4 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 208 Status Normal | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week Status 208 Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 52 Status Normal | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 260 Status Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 156 Status Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 52 Status Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 208 Status Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 156 Status Missing | 0 Participants |
| RO6885247 | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 104 Status Normal | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 52 Status Normal | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 208 Status Normal | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 52 Status Missing | 9 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 52 Status Normal | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 52 Status Missing | 1 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 104 Status Normal | 4 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 104 Status Missing | 5 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 104 Status Missing | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 104 Status Missing | 1 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 156 Status Normal | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 156 Status Missing | 9 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 156 Status Missing | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 156 Status Missing | 1 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 208 Status Missing | 9 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 208 Status Missing | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week Status 208 Missing | 1 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 260 Status Missing | 9 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 260 Status Missing | 0 Participants |
| Nusinersen | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 260 Status Missing | 1 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 156 Status Missing | 1 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 52 Status Normal | 1 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 260 Status Missing | 30 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 208 Status Normal | 1 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 208 Status Missing | 29 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 260 Status Missing | 0 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 208 Status Missing | 1 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 52 Status Missing | 27 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 104 Status Missing | 1 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Delayed: Week 260 Status Missing | 1 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 104 Status Missing | 0 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 104 Status Missing | 15 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week Status 208 Missing | 0 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 156 Status Normal | 4 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 104 Status Normal | 15 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 52 Status Normal | 3 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Normal: Week 156 Status Missing | 26 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 52 Status Missing | 0 Participants |
| Olesoxime | Number of Participants With Shift in Puberty Status From Baseline | Baseline Status Missing: Week 156 Status Missing | 0 Participants |
Primary
Plasma Trough Concentration (Ctrough) of Risdiplam
As pre-specified in the protocol, the PK data were not to be compared between participants who received different prior treatments (RO6885247, nusinersen, olesoxime and AVXS-101) received before entering this study, but to analyze the PK parameters of risdiplam. Hence, PK data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies.
Time frame: Predose at Year 5 visit
Population: PK population included all participants with at least one timepoint with a measurable drug concentration. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RO6885247 | Plasma Trough Concentration (Ctrough) of Risdiplam | 57.5 ng/mL |
Secondary
Survival of Motor Neuron (SMN) Protein Levels in Blood
SMA is caused by a homozygous deletion or mutation of the SMN 1 gene, which encodes SMN, an essential protein expressed in both neuronal and non-neuronal cells. In humans, there are two SMN genes, the SMN1 gene and its paralog SMN2. Risdiplam directly targets the underlying molecular deficiency of the disease and promotes the inclusion of exon 7 to generate full-length SMN2 mRNA, which therefore increases the production of functional SMN protein. As pre-specified in the protocol, the PD data were not to be compared between participants who received different prior treatments, but to analyze the PD parameters of risdiplam. Hence, PD data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies.
Time frame: Baseline and Year 5
Population: Pharmacodynamic (PD) population included all participants with at least one timepoint with a measurable PD marker. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RO6885247 | Survival of Motor Neuron (SMN) Protein Levels in Blood | Baseline | 3.35 ng/mL |
| RO6885247 | Survival of Motor Neuron (SMN) Protein Levels in Blood | Year 5 | 6.51 ng/mL |