Clinical trial of LMI070 given by mouth to Type I SMA infant patients.

Phase 1

• Conditions: Spinal Muscular Atrophy; MedDRA version: 20.1Level: LLTClassification code 10051203Term: Spinal muscular atrophy congenitalSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2014-002053-19-BG
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-07-31
• Study Completion: 2022-12-29
• Last Update Posted: 23 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 38

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
- Type 1 SMA, diagnosed with genetic confirmation of mutations in both alleles of the SMN1 gene, and with SMN2 copy number of 2.
- Impossibility / inappropriateness of treatment with nusinersen for one of the following conditions: unavailability of the drug, clinical choice (motivations expressed by the attending physician) or choice of the patient / caregiver.
- Age at screening up to 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 swallow solid and liquid even if feeding is used to support nutrition intake and must be in the 5th percentile for length or weight on the international growth curves and must be proportional in height and weight.
Are the trial subjects under 18? yes
Number of subjects for this age range: 44
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Specific for Part 2
- Use of gene transfer at any time or other investigational drugs within 14 days.
- Patients who have received nusinersen at any time prior to screening
- Intractable epilepsy
- Persistent (in the opinion of the Investigator) hypoxemia (O2 saturation awake <92% or O2 saturation asleep <91%, without ventilation support).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified