Summary

at Ekaterinburg, and other locations
study started
estimated completion

Description

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 is 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 is safe for long term use as well as that can provide durable efficacy optimal dosing regimen in patients with Type 1 SMA.

Official Title

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

Details

This is 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 and 2 are intended to be non-confirmatory. In Part 1 of the study, patients will be dosed once weekly with branaplam. The branaplam dose will be escalated in subsequent cohorts until MTD is determined or when sufficient PK results confirm that the MTD cannot be reached due to a potential pharmacokinetic plateau at higher doses. A decision to dose escalate the next cohort will be made after safety data have been collected for 14 days following the first dose (14-day DLT window). PK will be used to confirm that there is no accumulation of the compound.

Part 2 of the study will enroll new patients into one of up to 3 dose cohorts with once weekly dosing for 52 weeks. The branaplam dose will be escalated in subsequent cohorts after 6 patients have been enrolled and at least 3 patients from the previous cohort will have completed 13 weeks of treatment. After 52 weeks, patients may continue treatment if Novartis, the investigator and the independent DMC agree that this is in the best interest of the patient.

In all cases continuation of the treatment will be done at a dose selected as optimum, considering existing safety as well as efficacy data

Keywords

Spinal Muscular Atrophy Type 1 Spinal Muscular Atrophy Atrophy Muscular Atrophy Muscular Atrophy, Spinal branaplam

Eligibility

You can join if…

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

  • 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

You CAN'T join if...

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.
  • 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.

Locations

  • Novartis Investigative Site accepting new patients
    Ekaterinburg Russian Federation
  • Novartis Investigative Site accepting new patients
    Moscow 119049 Russian Federation
  • Novartis Investigative Site accepting new patients
    Moscow 127412 Russian Federation
  • Novartis Investigative Site accepting new patients
    Saint Petersburg 197341 Russian Federation
  • Novartis Investigative Site accepting new patients
    Ufa 450000 Russian Federation
  • Novartis Investigative Site accepting new patients
    Volgograd 400120 Russian Federation

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
Links
Sign up for this study
ID
NCT02268552
Phase
Phase 1/2
Study Type
Interventional
Last Updated