An open-label multi-part first-in-human study of oral LMI070 in infants with Type 1 spinal muscular atrophy
- Conditions
- motor neuron diseaseWerdnig-Hoffmann disease10029317
- Registration Number
- NL-OMON41741
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 2
- Written informed consent must be obtained from the parent / guardian before any assessment is performed.
- Type 1 SMA, diagnosed clinically (symptom onset < 6 months of age) and confirmed genetically (homozygous SMN1 gene deletion or mutation) plus SMN2 copy number of 2.
- Best supportive care in place and stable for at least 14 days before screening.
- Age at screening between 1 and 7 months, plus or minus 2 weeks.
- Must be able to demonstrate antigravity strength in both biceps.
- 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.
- Use of other investigational drugs within 14 days.
- Neurologic, neuromuscular or genetic disorders other than SMA.
- Anemia (Hgb < 8 g/dL), leukopenia (ANC < 2000/ml), or thrombocytopenia (<100,000/mL).
- Hepatic dysfunction (AST or ALT > 1.5 x ULN; total bilirubin < ULN).
- Renal dysfunction (eGFR < 80 ml/min).
- Clinically significant abnormalities in hematology or clinical chemistry parameters, as assessed by the Site Investigator, at screening that would render the subject unsuitable for inclusion.
- Hypoxemia (O2 saturation awake < 92% or O2 saturation asleep < 91%,without ventilation support) or requiring oral suctioning >2 per day.
- 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.
- Ongoing medical condition that according to the Site Investigator would interfere with the conduct and assessments of the study. Examples are medical disability other than SMA that would interfere withthe assessment of safety or would compromise the ability of the subject to undergo study procedures including be assessed by CHOP-INTEND motor scale.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoints Part 1:<br /><br>Physical Exam: Screening, D1 * D85 + EOS<br /><br>Vital signs: Screening, D1 * D85 + EOS<br /><br>ECG: Screening, D1, D8, D85 + EOS<br /><br>Safety: Screening, Baseline, D3, D8, D15, D29, D43, D57, D71, D85 + EOS<br /><br>Adverse Events: All Visits<br /><br><br /><br>Primary endpoints Part 2:<br /><br>Physical Exam: Screening, Baseline, D1 * D88 + EOS<br /><br>Vital signs: Screening, Baseline, D1 * D88 + EOS<br /><br>ECG: Screening, D1, D8, D88 + EOS<br /><br>Safety: Screening, Baseline, D8, d15, D2, D29, D36, D43, D50, D57, D64, D71,<br /><br>D88 + EOS<br /><br>Adverse Events: All Visits</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints Part 1:<br /><br>PK: D1 (Pre-dose + 1, 2, 4, 8 & 24 hours post-dose), D2, D3, D5, D8, D29, D43<br /><br>Ultrasound: Baseline, D85 + EOS<br /><br>Growth measurements: Screening, D1, D8-D85 + EOS<br /><br>Respiratory function: Baseline, D8-D85 +EOS<br /><br>CHOP-INTEND: Baseline, D36, D85 + EOS<br /><br><br /><br>Secondary Endpoints Part 2:<br /><br>PK: D1 (Pre-dose + 1, 2, 4, 8 & 24 hours post-dose), D2, D3, D5, D8, D29, D43,<br /><br>D57 (Pre-dose + 2, 4, 8 & 24 hours post-dose), D59, D62<br /><br>Ultrasound: Baseline, D88 + EOS<br /><br>Growth measurements: Screening, D1, D8-D57, D64, D71, D88 + EOS<br /><br>Respiratory function: Baseline, D8-D57, D64, D71, D88 + EOS<br /><br>CHOP-INTEND: Baseline, D15, D36, D57, D88 + EOS<br /><br>CMAP: Baseline, D88 + EOS</p><br>