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

ClinicalTrials.gov Identifier: NCT02268552

Novartis Reference Number: CLMI070X2201

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
Spinal Muscular Atrophy
Phase 
Phase 1
Phase 2
Overall status 
Active, not recruiting
Enrollment count 
40 participants
Start date 
Apr 02, 2015
Completion date 
Jul 23, 2020
Gender 
All
Age(s)
182 Years and older (Child)

Interventions

Drug
branaplam

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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.

Study Locations

Belgium
Novartis Investigative Site
-
Gent, 9000
-
Belgium
Novartis Investigative Site
-
Leuven, 3000
-
Belgium
Bulgaria
Novartis Investigative Site
-
Sofia, 1606
-
Bulgaria
Denmark
Novartis Investigative Site
-
Copenhagen, 2100 O
-
Denmark
Germany
Novartis Investigative Site
-
Essen, 45147
-
Germany
Italy
Novartis Investigative Site
-
Roma, 00165
ITA
Italy
Novartis Investigative Site
-
Milano, 20133
MI
Italy
Poland
Novartis Investigative Site
-
Warsaw, 04 730
-
Poland
Novartis Investigative Site
-
Wroclaw, 50 420
-
Poland
Russian Federation
Novartis Investigative Site
-
Ekaterinburg,
-
Russian Federation
Novartis Investigative Site
-
Moscow, 119049
-
Russian Federation
Novartis Investigative Site
-
Moscow, 127412
-
Russian Federation
Novartis Investigative Site
-
Saint Petersburg, 197341
-
Russian Federation
Novartis Investigative Site
-
Volgograd, 400120
-
Russian Federation

Have a question?

Call 1-999-669-6682 or email [email protected]