A Phase 1/2 interventional study of branaplam in Spinal Muscular Atrophy, sponsored by Novartis Pharmaceuticals. Completed at 14 sites in 7 countries. Open to participants aged 28 Days to 182 Days. Per ClinicalTrials.gov, last updated 2025-04-09.
Sponsored by Novartis Pharmaceuticals · Phase 1/2, Interventional, and Treatment
An open-label, multi-part, first-in-human study of oral branaplam in infants with Type 1 spinal muscular atrophy. The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy after 13 weeks; and to estimate the Maximum Tolerated Dose (MTD) of orally administered branaplam; and to identify the dose that was safe for long term use as well as that can provide durable efficacy optimal dosing regimen in patients with Type 1 SMA.
This was an open-label, multi-part, first-in-human, proof of concept study in infants with Type 1 spinal muscular atrophy who have exactly 2 copies of SMN2, to evaluate safety, tolerability, PK, PD and efficacy of oral branaplam after 13 weeks treatment.
Parts 1,2 and 3 were intended to be non-confirmatory.
In Part 1 of the study, patients were dosed once weekly with branaplam. The branaplam dose was escalated in subsequent cohorts until MTD was determined or when sufficient PK results confirmed that the MTD could not be reached due to a potential pharmacokinetic plateau at higher doses. A decision to dose escalate the next cohort was made after safety data was collected for 14 days following the first dose (14-day DLT window). PK was used to confirm that there was no accumulation of the compound. After 13 weeks treatment, participants in part 1 could enter an extension treatment phase until they discontinued from the study or were transferred into part 3.
Part 2 of the study enrolled new patients into one 2 dose cohorts with once weekly dosing for 52 weeks. The branaplam dose was escalated in subsequent cohorts after 6 patients were enrolled and at least 3 patients from the previous cohort completed 13 weeks of treatment. After 52 weeks, patients may have continued treatment in part 3 if it was in the best interest of the patient.
Part 3, participants from part 1 and 2 who have completed at least 52 weeks of banaplam treatment were elegible to continue receiving treatment as long as in the best interest of the patient. In all cases continuation of the treatment was done at a dose selected as optimum, considering existing safety as well as efficacy data.
494 studies on the registry are indexed under Muscular Atrophy; 94 are open to participants now.
This study's enrollment of 40 is above the median of 33 across 335 interventional studies indexed under Muscular Atrophy.
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Common for both Parts 1 and 2:
Specific for Part 1
Specific for Part 2
Exclusion Criteria:
Common for both Parts 1 and 2:
Specific for Part 1
Specific for Part 2
branaplam Treatment
Drug: branaplam
Number of Participants With Dose Limiting Toxicities (DLT) in Part 1 - Safety Analysis Set (SAS)
A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant therapies that occurs within the first 14 days of treatment with LMI070 and meets any of the criteria for blood and lymphatic system disorders, gastrointestinal disorders, investigations and other toxicities considered clinically significant.
Time frame: Baseline up to 2 weeks for Part 1
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events and Deaths- SAS
TEAEs are defined as adverse events starting on or after the first dose of study treatment that were absent pre-treatment, or events present prior to the first dose but increased in severity after the first dose. Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post last treatment.
Time frame: Baseline up to approximately 83 months
Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUCinf) After a Single Dose - Part 1 - Pharmacokinetics Analysis Set (PAS)
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume\]
Time frame: from 0 h to 168 h after first/single dose
Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUCinf) for All Observation Periods - Part 1 - PAS
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume\] for all observations. AUC values used for comparison are combined from AUCinf values after single dose and AUC 0-168h values after repeated administration.
Time frame: from 0 h to 168 h after first/single dose
Summary of Plasma Pharmacokinetic (PK) Parameter Cmax After a Single Dose - Part 1 - PAS
The observed maximum plasma concentration following drug administration \[mass / volume).
Time frame: from 0 h to 168 h after first/single dose
Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for All Observation Periods - Part 1 - PAS
The observed maximum plasma (or serum or blood) concentration following drug administration \[mass / volume
Time frame: from 0 h to 168 h after first/single dose
Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUC) After a Single Dose - Part 2 - PAS
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume)
Time frame: from 0 h to 168 h after first/single dose
Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUC) for All Observation Periods - Part 2 - PAS
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume). AUC values used for comparison are combined from AUCinf values after single dose and AUC0-168h values after repeated administration.
Time frame: from 0 h to 168 h after first/single dose
Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for a Single Dose - Part 2 - PAS
The observed maximum plasma (or serum or blood) concentration following drug administration \[mass / volume)
Time frame: from 0 h to 168 h after first/single dose
Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for All Observation Periods - Part 2 - PAS
The observed maximum plasma (or serum or blood) concentration following drug administration \[mass / volume)
Time frame: from 0 h to 168 h after first/single dose
Change From Baseline in Growth Parameters: Chest Circumference, Head Circumference and Body Length - Full Analysis Set (FAS)
The effect of branaplam on growth parameters: Length (measured from the top of the head to the sole of the foot), Head circumference and Chest circumference (measured across nipple line). Mean change from baseline in cm is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline, Week 52 and Month 6 of Part 3
Change From Baseline in Growth Parameter: Body Weight - FAS
The effect of Branaplam on body weight in Kg was measured using a weight scale. Mean change from baseline in Kg is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline, Week 52 and Month 6 of Part 3
Change From Baseline in Respiratory Function: Pulse Oximetry - FAS
The effect of branaplam on pulse oximetry in percentage of oxygen saturation was evaluated using a probe that measures oxygen in the blood. Mean change from baseline in percentage of oxygen saturation is reported. Negative numbers indicate a decrease from baseline In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline, Week 52 and Month 6 of Part 3
Change From Baseline in Respiratory Function: Respiratory Rate - FAS
The effect of branaplam on respiratory rate was evaluated by counting the number of breaths for one minute. Mean change from baseline in breaths per minute is reported" In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline, Week 52 and Month 6 of Part 3
Number of Participants With Presence of Paradoxical Breathing - FAS
A paradoxical breathing occurs when one compartment moves out of phase compared to another one. In SMA type I, paradoxical breathing is often a sign of breathing problems where the pulmonary ribcage moves inward during inspiration rather than outward while the abdomen expands. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline, Week 52 and Month 6 of Part 3
Change From Baseline in Respiratory Function: Chest Circumference During Quiet Breathing - End of Inspiration and Expiration - FAS
The effect of branaplam on respiratory status was evaluated by measuring the circumference of the ribcage while taking a breathe in and out while quiet or sleeping. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline, Week 52 and Month 6 of Part 3
Summary of CHOP INTEND Total Score - Parts 1 and 3 and Parts 2 and 3 - FAS
CHOP INTEND is a motor test measure for SMA Type 1 and similarly weak infants with neuromuscular disease. The CHOP INTEND provides a useful measure of motor skills and strength in this population. It is a 16 item, 64 point scale. Each item (motor skill) is given a score from zero to 4: zero indicates can't complete the movement, 1 to 3 indicates partial performance and a 4 indicates person can complete the movement on their own without assistance. These scores are added up to a possible total score of 64 and higher scores indicate better outcomes. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline, Week 52 and Month 6 of Part 3
Number of Participants Fed Orally or by Feeding Tube for Parts 1 and 3 and Parts 2 and 3 - FAS
To evaluate the efficacy of branaplam on preservation of oral feeding In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline up Week 78
Number of Participants and HINE Motor Subscale Milestones (Ability to Sit, Stand or Walk Without Support) - FAS
HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Week 52 and Month 6 of Part 3
Summary of Hammersmith Infant Neurologic Examination Section 2 (HINE-2) - FAS
HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Week 52 and Month 6 of Part 3
Ventilation Use for Parts 1 and 3 and Parts 2 and 3 - FAS
BiBAP (bilevel positive airway pressure) ventilation is a 2 level breathing support which has a tube that connects to a mask. It provides a different level of air pressure for inhalation vs. exhalation, whereas a CPAP (continuous positive airway pressure) only pumps one level of air pressure but is also non-invasiive. Invasive ventilation is delivered via an endotracheal or tracheostomy tube. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
Time frame: Baseline up to 82 months
| Milestone | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|---|---|---|---|---|
| Started | 2 | 2 | 2 | 4 | 3 | 0 | 0 |
| Completed | 1 | 1 | 1 | 1 | 3 | 0 | 0 |
| Not completed | 1 | 1 | 1 | 3 | 0 | 0 | 0 |
| Withdrew: Death | 1 | 1 | 1 | 2 | 0 | 0 | 0 |
| Withdrew: Subject/guardian decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Milestone | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 10 | 15 |
| Completed | 0 | 0 | 0 | 0 | 0 | 10 | 12 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Withdrew: Subject/guardian decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Milestone | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|---|---|---|---|---|
| Started | 1 | 1 | 1 | 1 | 3 | 10 | 12 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 1 | 1 | 1 | 1 | 3 | 10 | 12 |
| Withdrew: Death | 0 | 1 | 1 | 1 | 1 | 1 | 0 |
| Withdrew: Early termination of trial | 1 | 0 | 0 | 0 | 2 | 9 | 11 |
| Withdrew: Subject/guardian decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant therapies that occurs within the first 14 days of treatment with LMI070 and meets any of the criteria for blood and lymphatic system disorders, gastrointestinal disorders, investigations and other toxicities considered clinically significant.
| Participants | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 |
|---|---|---|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLT) in Part 1 - Safety Analysis Set (SAS) | 0 | 0 | 0 | 0 | 0 |
TEAEs are defined as adverse events starting on or after the first dose of study treatment that were absent pre-treatment, or events present prior to the first dose but increased in severity after the first dose. Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post last treatment.
| Participants | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|---|---|---|---|---|
| Participants with adverse events | 2 | 2 | 2 | 4 | 3 | 10 | 15 |
| Participants with serious adverse events | 2 | 2 | 2 | 4 | 3 | 8 | 11 |
| Deaths | 1 | 2 | 2 | 3 | 1 | 1 | 2 |
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume\]
| h*ng/mL | Part 1 LMI070 Overall |
|---|---|
| 0.321 mg/kg - Actual | 378 ± 31.9 |
| 0.654 mg/kg - Actual | 892 ± 12.3 |
| 1.39 mg/kg - Actual | 1820 |
| 2.49 mg/kg - Actual | 3310 ± 1340 |
| 2.94 mg/kg - Actual | 3800 ± 1590 |
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume\] for all observations. AUC values used for comparison are combined from AUCinf values after single dose and AUC 0-168h values after repeated administration.
| h*ng/mL | Part 1 LMI070 Overall |
|---|---|
| 0.299 mg/kg - Actual | 413 ± 98.3 |
| 0.644 mg/kg - Actual | 761 ± 170 |
| 1.30 mg/kg - Actual | 1340 ± 381 |
| 2.52 mg/kg - Actual | 3310 ± 850 |
| 2.95 mg/kg - Actual | 4210 ± 1030 |
The observed maximum plasma concentration following drug administration \[mass / volume).
| ng/mL | Part 1 LMI070 Overall |
|---|---|
| 0.321 mg/kg - Actual | 9.10 ± 1.22 |
| 0.654 mg/kg - Actual | 18.6 ± 1.63 |
| 1.39 mg/kg - Actual | 55.6 |
| 2.49 mg/kg - Actual | 53.2 ± 9.50 |
| 2.94 mg/kg - Actual | 72.4 ± 16.7 |
The observed maximum plasma (or serum or blood) concentration following drug administration \[mass / volume
| ng/mL | Part 1 LMI070 Overall |
|---|---|
| 0.299 mg/kg - Actual | 8.84 ± 3.58 |
| 0.644 mg/kg - Actual | 15.3 ± 4.10 |
| 1.30 mg/kg - Actual | 37.8 ± 12.8 |
| 2.51 mg/kg - Actual | 69.1 ± 15.7 |
| 2.95 mg/kg - Actual | 96.5 ± 32.7 |
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume)
| h*ng/mL | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|
| Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUC) After a Single Dose - Part 2 - PAS | 1150 ± 357 | 4060 ± 734 |
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity \[mass x time / volume). AUC values used for comparison are combined from AUCinf values after single dose and AUC0-168h values after repeated administration.
| h*ng/mL | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|
| Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUC) for All Observation Periods - Part 2 - PAS | 1020 ± 278 | 3470 ± 909 |
The observed maximum plasma (or serum or blood) concentration following drug administration \[mass / volume)
| ng/mL | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|
| Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for a Single Dose - Part 2 - PAS | 22.0 ± 5.70 | 82.0 ± 22.5 |
The observed maximum plasma (or serum or blood) concentration following drug administration \[mass / volume)
| ng/mL | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|
| Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for All Observation Periods - Part 2 - PAS | 21.7 ± 5.71 | 77.4 ± 27.5 |
The effect of branaplam on growth parameters: Length (measured from the top of the head to the sole of the foot), Head circumference and Chest circumference (measured across nipple line). Mean change from baseline in cm is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| cm | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Chest - Week 52 | 4.68 ± 2.4769 | 5.656 ± 3.0167 |
| Chest - P3 Month 6 | 14.750 ± 0548 | 8.582 ± 2.7423 |
| Head -Week 52 | 5.030 ± 1.1235 | 5.111 ± 1.3407 |
| Head -P3 Month 6 | 9.717 ± 1.8766 | 6.359 ± 1.2971 |
| Length - Week 52 | 16.950 ± 3.7825 | 16.942 ± 4.5806 |
| Length - P3 Month 6 | 52.140 ± 9.8766 | 22.944 ± 3.7686 |
The effect of Branaplam on body weight in Kg was measured using a weight scale. Mean change from baseline in Kg is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| kg | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Week 52 | 2.739 ± 1.3545 | 3.145 ± 1.5089 |
| P3 Month 6 | 9.546 ± 3.5069 | 4.402 ± 1.3250 |
The effect of branaplam on pulse oximetry in percentage of oxygen saturation was evaluated using a probe that measures oxygen in the blood. Mean change from baseline in percentage of oxygen saturation is reported. Negative numbers indicate a decrease from baseline In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| percentage | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Week 52 | -0.8 ± 2.59 | -0.1 ± 1.56 |
| P3 Month 6 | -0.7 ± 2.58 | 0.0 ± 1.83 |
The effect of branaplam on respiratory rate was evaluated by counting the number of breaths for one minute. Mean change from baseline in breaths per minute is reported" In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| breaths per minute | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Week 52 | 41.3 ± 7.57 | 40.5 ± 13.46 |
| P3 Month 6 | 29.2 ± 6.59 | 37.2 ± 8.95 |
A paradoxical breathing occurs when one compartment moves out of phase compared to another one. In SMA type I, paradoxical breathing is often a sign of breathing problems where the pulmonary ribcage moves inward during inspiration rather than outward while the abdomen expands. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| Participants | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Week 52 | 5 | 15 |
| P3 Month 6 | 4 | 14 |
The effect of branaplam on respiratory status was evaluated by measuring the circumference of the ribcage while taking a breathe in and out while quiet or sleeping. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| cm | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Week 52 - end of inspiration | — | 5.964 ± 3.6345 |
| P3 Month 6 - end of inspiration | — | 8.535 ± 3.3083 |
| Week 52 - end of expiration | — | 6.033 ± 3.9466 |
| P3 Month 6 - end of expiration | — | 9.147 ± 3.5755 |
CHOP INTEND is a motor test measure for SMA Type 1 and similarly weak infants with neuromuscular disease. The CHOP INTEND provides a useful measure of motor skills and strength in this population. It is a 16 item, 64 point scale. Each item (motor skill) is given a score from zero to 4: zero indicates can't complete the movement, 1 to 3 indicates partial performance and a 4 indicates person can complete the movement on their own without assistance. These scores are added up to a possible total score of 64 and higher scores indicate better outcomes. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| scores on a scale | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Week 52 | 38.1 ± 8.69 | 43.6 ± 6.79 |
| Part 3, Month 6 | 26.0 | 44.7 ± 8.73 |
To evaluate the efficacy of branaplam on preservation of oral feeding In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| participants | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Only exclusively orally fed | 3 | 18 |
| Only exclusively tube fed | 0 | 0 |
| Started on orally fed, switched to tube fed | 0 | 2 |
| Started on tube fed, switched to orally fed | 0 | 0 |
| Other (mixture of both tube and oral feeding) | 8 | 5 |
HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| participants | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Week 52 Sitting - Stable independent sit or Pivots (rotates) | 1 | 1 |
| Week 52 Standing - Supports weight | 0 | 2 |
| Week 52: Walking - Makes any attempt (i.e., bounces) | 0 | 1 |
| Part 3, Month 6: Sitting - Stable independent sit or Pivots (rotates) | 0 | 4 |
| Part 3, Month 6: Standing - Supports weight | 0 | 5 |
| Part 3, Month 6: Walking - Makes any attempt (i.e., bounces) | 0 | 2 |
HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| total scores | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Week 52 | 3.3 ± 2.31 | 4.9 ± 3.44 |
| Part 3 Month 6 | 3.0 ± 2.12 | 7.7 ± 4.82 |
BiBAP (bilevel positive airway pressure) ventilation is a 2 level breathing support which has a tube that connects to a mask. It provides a different level of air pressure for inhalation vs. exhalation, whereas a CPAP (continuous positive airway pressure) only pumps one level of air pressure but is also non-invasiive. Invasive ventilation is delivered via an endotracheal or tracheostomy tube. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1\&3 and Part 2\&3) irrespective of study dose or route of administration.
| participants | Parts 1 & 3 Overall | Parts 2 & 3 Overall |
|---|---|---|
| Non-invasive ventilation - BiPAP | 9 | 18 |
| Non-invasive ventilation - CPAP | 3 | 2 |
| Invasive ventilation | 4 | 5 |
Collected over Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post last treatment up a maximum of 83 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1 LMI070 6mg/m2 | 1/2 (50%) | 2/2 (100%) | 2/2 (100%) |
| Part 1 LMI070 12mg/m2 | 2/2 (100%) | 2/2 (100%) | 2/2 (100%) |
| Part 1 LMI070 24mg/m2 | 2/2 (100%) | 2/2 (100%) | 2/2 (100%) |
| Part 1 LMI070 48mg/m2 | 3/4 (75%) | 4/4 (100%) | 4/4 (100%) |
| Part 1 LMI070 60mg/m2 | 1/3 (33.3%) | 3/3 (100%) | 3/3 (100%) |
| Part 2 LMI070 0.625 mg/kg | 1/10 (10%) | 8/10 (80%) | 10/10 (100%) |
| Part 2 LMI070 2.5 mg/kg | 2/15 (13.3%) | 11/15 (73.3%) | 15/15 (100%) |
| Event | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 2/2 | 2/2 | 1/2 | 2/4 | 2/3 | 4/10 | 7/15 |
| DehydrationMetabolism and nutrition disorders | 0/2 | 2/2 | 0/2 | 0/4 | 0/3 | 0/10 | 0/15 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 1/2 | 0/2 | 0/2 | 2/4 | 2/3 | 2/10 | 2/15 |
| BradycardiaCardiac disorders | 0/2 | 0/2 | 1/2 | 0/4 | 0/3 | 0/10 | 0/15 |
| Cardiac arrestCardiac disorders | 0/2 | 0/2 | 1/2 | 0/4 | 0/3 | 1/10 | 0/15 |
| Left ventricular hypertrophyCardiac disorders | 0/2 | 0/2 | 1/2 | 0/4 | 0/3 | 0/10 | 0/15 |
| ConstipationGastrointestinal disorders | 0/2 | 0/2 | 1/2 | 0/4 | 0/3 | 0/10 | 0/15 |
| DiarrhoeaGastrointestinal disorders | 0/2 | 1/2 | 0/2 | 0/4 | 0/3 | 0/10 | 0/15 |
| Intestinal ischaemiaGastrointestinal disorders | 0/2 | 1/2 | 0/2 | 0/4 | 0/3 | 0/10 | 0/15 |
| CellulitisInfections and infestations | 1/2 | 0/2 | 0/2 | 0/4 | 0/3 | 0/10 | 0/15 |
| Event | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg |
|---|---|---|---|---|---|---|---|
| ConstipationGastrointestinal disorders | 1/2 | 1/2 | 2/2 | 0/4 | 2/3 | 7/10 | 3/15 |
| DiarrhoeaGastrointestinal disorders | 1/2 | 1/2 | 1/2 | 1/4 | 3/3 | 2/10 | 2/15 |
| VomitingGastrointestinal disorders | 2/2 | 1/2 | 2/2 | 2/4 | 3/3 | 2/10 | 2/15 |
| PyrexiaGeneral disorders | 2/2 | 2/2 | 2/2 | 2/4 | 3/3 | 7/10 | 6/15 |
| GastroenteritisInfections and infestations | 2/2 | 1/2 | 0/2 | 0/4 | 2/3 | 0/10 | 0/15 |
| RhinitisInfections and infestations | 1/2 | 0/2 | 0/2 | 2/4 | 3/3 | 2/10 | 4/15 |
| Upper respiratory tract infectionInfections and infestations | 1/2 | 1/2 | 0/2 | 2/4 | 3/3 | 4/10 | 3/15 |
| Urinary tract infectionInfections and infestations | 1/2 | 1/2 | 1/2 | 0/4 | 3/3 | 2/10 | 2/15 |
| Neutrophil count decreasedInvestigations | 2/2 | 0/2 | 0/2 | 0/4 | 0/3 | 0/10 | 0/15 |
| ScoliosisMusculoskeletal and connective tissue disorders | 2/2 | 0/2 | 1/2 | 0/4 | 2/3 | 4/10 | 3/15 |
| Age, Continuous(months) | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|
| Mean | 3.0 ± 1.41 | 4.5 ± 0.71 | 3.5 ± 2.12 | 3.8 ± 1.71 | 5.3 ± 2.08 | 4.38 ± 1.521 | 3.81 ± 1.188 | 4.21 ± 1.481 |
| Sex: Female, Male(Participants) | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 1 | 0 | 2 | 3 | 2 | 5 | 9 | 22 |
| Male | 1 | 2 | 0 | 1 | 1 | 5 | 6 | 16 |
| Race/Ethnicity, Customized(Participants) | Part 1 LMI070 6mg/m2 | Part 1 LMI070 12mg/m2 | Part 1 LMI070 24mg/m2 | Part 1 LMI070 48mg/m2 | Part 1 LMI070 60mg/m2 | Part 2 LMI070 0.625 mg/kg | Part 2 LMI070 2.5 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|
| Caucasian | 2 | 2 | 1 | 3 | 2 | 10 | 14 | 34 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Other | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 |
| Black | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
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Plan to share: Undecided — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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