Spinal Muscular AtrophyPhase 1/2NCT02268552
An Open Label Study of LMI070 (Branaplam) in Type 1 Spinal Muscular Atrophy (SMA)
A Phase 1/2 study testing branaplam in people with Spinal Muscular Atrophy, run by Novartis Pharmaceuticals at 14 sites in 7 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 28 to 182 days
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- branaplam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 14 sitesin 7 countries
- Study dates
- 2 Apr 2015to 29 Dec 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 to 182 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Common for both Parts 1 and 2:
- Type 1 SMA, diagnosed clinically, with symptom onset <6 months of age and genetic confirmation of mutations in both alleles of the SMN1 gene, and with SMN2 copy number of 2.
- Best supportive care in place and stable for at least 14 days before screening.
- Must be able to demonstrate antigravity strength in both biceps. At birth gestational age >32 weeks and body weight at birth >2 kg.
- Must live within 2 hours drive of study center. Clearance should be obtained from the site investigator and sponsor if the patient resides more than 2 hours ground travel from the study center
- Specific for Part 1
Show all 13Show fewer
- Age at screening between 1 and 7 months
- Must have or agree to have placement of feeding tube for enteral access via nasogastric (NG), nasojejunal (NJ), percutaneous gastrostomy (PEG), or percutaneous jejunostomy (PEJ) tube for administration of branaplam (for patients in whom branaplam cannot be administered orally ; NG tube may be removed between doses).
- Specific for Part 2
- Age at screening between 30 and 180 days of age
- Must have or agree to have placement of feeding tube for enteral access via nasogastric (NG), nasojejunal (NJ), percutaneous gastrostomy (PEG), or percutaneous jejunostomy (PEJ) tube for administration of branaplam (for the first administration only and for patients in whom branaplam cannot be administered orally; NG tube may be removed between doses).
- Minimum CHOP INTEND score of 15 at baseline
- Must be able to feed orally for all nutritional needs and be greater than the 2nd percentile for weight on the standard growth curves for the country of origin
Who cannot join
- Common for both Parts 1 and 2:
- Neurologic, or neuromuscular conditions other than SMA.
- Anemia, leukopenia, neutropenia or thrombocytopenia
- Hepatic dysfunction
- Age adjusted renal dysfunction
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
Show all 18Show fewer
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
- Excluding SMA, any medically unstable condition including cardiomyopathy, hepatic dysfunction, kidney disorder, endocrine disorder, GI disorders, prematurity of <32 weeks gestation, metabolic disorders, severe respiratory compromise and significant brain abnormalities or injuries including hypoxic-ischemic encephalopathy.
- Current diagnosis of cardiac and/or vascular abnormalities or ECG abnormalities
- Acute or ongoing medical condition that, according to the Site Investigator and discussed with sponsor, would interfere with the conduct and assessments of the study. Examples are medical disability other than SMA that would interfere with the assessment of safety or would compromise the ability of the subject to undergo study procedures including be assessed by CHOP INTEND motor scale, changes in hematologic parameters or gastrointestinal dysfunction that would compromise the ability of adequate assessment of safety
- Specific for Part 1
- Use of other investigational drugs within 14 days.
- Intractable seizure disorder (other than inactive febrile seizures).
- Persistent (in the opinion of the Investigator) hypoxemia (O2 saturation awake <92% or O2 saturation asleep <91%, without ventilation support) or requiring oral suctioning >2 per day, or presence of a tracheostomy.
- Specific for Part 2
- Use of nusinersen or gene transfer at any time or other investigational drugs within 14 days.
- Intractable epilepsy
- Persistent (in the opinion of the Investigator) hypoxemia (O2 saturation awake <92% or O2 saturation asleep <91%, without ventilation support), or presence of a tracheostomy.
Trial locations and contacts
14 sites in 7 countries.
14 sites in 7 countries
Russia5 sites
Novartis Investigative Site
Moscow, 119049
Novartis Investigative Site
Moscow, 127412
Novartis Investigative Site
Saint Petersburg, 197341
Novartis Investigative Site
Volgograd, 400120
Novartis Investigative Site
Yekaterinburg, 620134
Belgium2 sites
Novartis Investigative Site
Ghent, 9000
Novartis Investigative Site
Leuven, 3000
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Roma, RM, 00165
Poland2 sites
Novartis Investigative Site
Warsaw, 04 730
Novartis Investigative Site
Wroclaw, 50 420
About this study
Official title: An Open Label Multi-part First-in-human Study of Oral LMI070 in Infants With Type 1 Spinal Muscular Atrophy
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.
Read the detailed description
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.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- branaplam
- Keywords
- Type 1 Spinal Muscular Atrophy
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
branaplamDrug
| Study group | Role | What they receive |
|---|---|---|
| branaplam | Experimental | branaplam Treatment Receives: Drug: branaplam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline up to approximately 83 months
Secondary outcomes (19)
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]
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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)
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline up to 82 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2014 (estimated)
- Study start2 Apr 2015
- Primary completion29 Dec 2022
- Study completion29 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02268552
- Sponsor's protocol ID
- CLMI070X2201
- Status last verified
- Mar 2025
- First submitted
- 1 Oct 2014
- Last updated
- 9 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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
Publications
Keller CG, Shin Y, Monteys AM, Renaud N, Beibel M, Teider N, Peters T, Faller T, St-Cyr S, Knehr J, Roma G, Reyes A, Hild M, Lukashev D, Theil D, Dales N, Cha JH, Borowsky B, Dolmetsch R, Davidson BL, Sivasankaran R. An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion. Nat Commun. 2022 Mar 3;13(1):1150. doi: 10.1038/s41467-022-28653-6.
PubMed 35241644
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Multi-part First-in-human Study of Oral LMI070 in Infants With Type 1 Spinal Muscular Atrophy
- ClinicalTrials.gov ID
- NCT02268552
- Acronym / sponsor ID
- CLMI070X2201
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Type 1 Spinal Muscular Atrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 2 Apr 2015 (actual)
- Primary completion
- 29 Dec 2022 (actual)
- Study completion
- 29 Dec 2022 (actual)
- First posted
- 20 Oct 2014 (estimated)
- Results
- Posted 9 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| branaplam | Experimental | Drug: branaplambranaplam Treatment |
Who may qualify
- Ages
- 28 to 182 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- Type 1 SMA, diagnosed clinically, with symptom onset <6 months of age and genetic confirmation of mutations in both alleles of the SMN1 gene, and with SMN2 copy number of 2.
- Best supportive care in place and stable for at least 14 days before screening.
- Must be able to demonstrate antigravity strength in both biceps. At birth gestational age >32 weeks and body weight at birth >2 kg.
- Must live within 2 hours drive of study center. Clearance should be obtained from the site investigator and sponsor if the patient resides more than 2 hours ground travel from the study center
- Specific for Part 1
Key exclusion criteria (18 listed)
- Neurologic, or neuromuscular conditions other than SMA.
- Anemia, leukopenia, neutropenia or thrombocytopenia
- Hepatic dysfunction
- Age adjusted renal dysfunction
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| branaplam | Drug | branaplam |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLT) in Part 1 - Safety Analysis Set (SAS)
Time frame: Baseline up to 2 weeks for Part 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events and Deaths- SAS
Time frame: Baseline up to approximately 83 months
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.
19 secondary outcomes
Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUCinf) After a Single Dose - Part 1 - Pharmacokinetics Analysis Set (PAS)
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
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
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
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
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
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
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
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)
Time frame: Baseline, Week 52 and Month 6 of Part 3
Change From Baseline in Growth Parameter: Body Weight - FAS
Time frame: Baseline, Week 52 and Month 6 of Part 3
Change From Baseline in Respiratory Function: Pulse Oximetry - FAS
Time frame: Baseline, Week 52 and Month 6 of Part 3
Change From Baseline in Respiratory Function: Respiratory Rate - FAS
Time frame: Baseline, Week 52 and Month 6 of Part 3
Number of Participants With Presence of Paradoxical Breathing - FAS
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
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
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
Time frame: Baseline up Week 78
Number of Participants and HINE Motor Subscale Milestones (Ability to Sit, Stand or Walk Without Support) - FAS
Time frame: Week 52 and Month 6 of Part 3
Summary of Hammersmith Infant Neurologic Examination Section 2 (HINE-2) - FAS
Time frame: Week 52 and Month 6 of Part 3
Ventilation Use for Parts 1 and 3 and Parts 2 and 3 - FAS
Time frame: Baseline up to 82 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35241644Keller CG, Shin Y, Monteys AM, Renaud N, Beibel M, Teider N, Peters T, Faller T, St-Cyr S, Knehr J, Roma G, Reyes A, Hild M, Lukashev D, Theil D, Dales N, Cha JH, Borowsky B, Dolmetsch R, Davidson BL, Sivasankaran R. An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion. Nat Commun. 2022 Mar 3;13(1):1150. doi: 10.1038/s41467-022-28653-6.
- Individual participant dataSharing planned: 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing branaplam in people with Spinal Muscular Atrophy, run by Novartis Pharmaceuticals at 14 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Russia, Belgium, Italy, Poland, Bulgaria and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLT) in Part 1 - Safety Analysis Set (SAS) (time frame: Baseline up to 2 weeks for Part 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02268552, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.