NCT02268552

An Open Label Study of LMI070 (Branaplam) in Type 1 Spinal Muscular Atrophy (SMA)

An Open Label Multi-part First-in-human Study of Oral LMI070 in Infants With Type 1 Spinal Muscular Atrophy

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 28 Days – 182 Days
• Healthy volunteers: Not accepted

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 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.

Conditions

• Spinal Muscular Atrophy

Interventions

Type	Name	Description
DRUG	branaplam

Timeline

• Start date: 2015-04-02
• Primary completion: 2022-12-29
• Completion: 2022-12-29
• First posted: 2014-10-20
• Last updated: 2025-04-09
• Results posted: 2025-04-09

Locations

14 sites across 7 countries: Belgium, Bulgaria, Denmark, Germany, Italy, Poland, Russia