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

• Register: EUCTR
• Last refreshed on: 2 March 2022
• Main ID: EUCTR2014-002053-19-IT
• Date of registration: 27/10/2014
• Prospective Registration: Yes
• Primary sponsor: NOVARTIS FARMA S.p.A.
• Public title: Clinical trial of LMI070 given my mouth to Type I SMA infant patients.
• Scientific title: An open-label multi-part first-in-human study of oral LMI070 in infants with Type 1 spinal muscular atrophy - CLMI070X2201
• Date of first enrolment: 01/04/2015
• Target sample size: 22
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002053-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, Czech Republic, Denmark, European Union, Germany, Hungary, Italy, Netherlands, Poland, United States

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA S.p.A.

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
•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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 22
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:
•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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Spinal Muscular Atrophy

Intervention(s)

Product Name: NA
Product Code: LMI070
Pharmaceutical Form: Oral solution
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: LMI070
Other descriptive name: NA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 3.5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: See Above

Secondary Objective: Part 1
-To evaluate LMI070 pharmacokinetics in serum after single and repeated doses of LMI070.
-To evaluate the effect of LMI070 on muscle by ultrasound.
-To evaluate the effect of LMI070 on growth parameters.
-To evaluate the effect of LMI070 on respiratory function
-To evaluate the effect of LMI070 on infant motor development.

In addition to the above for Part 2:
-To evaluate the efficacy of LMI070 on motor and developmental milestones
-To evaluate the efficacy of LMI070 on ulnar nerve compound action potential [CMAP] (optional)

Primary end point(s): Primary endpoint for Part 1:
Physical Exam : Screening, D1 – D85 + EOS
Vital signs: Screening, D1 – D85 + EOS
ECG : Screening, D1, D8, D85 + EOS
Safety : Screening, Baseline, D3, D8, D15, D29, D43, D57, D71, D85 + EOS
Adverse Events: All Visits

Primary endpoint Part 2
Physical Exam – Screening, Baseline, D1 – D88 + EOS
Vital signs - Screening, Baseline, D1 – D88 + EOS
ECG - Screening, D1, D8, D88 + EOS
Safety – Screening, Baseline, D8, d15, D2, D29, D36, D43, D50, D57, D64, D71, D88 + EOS
Adverse Events – All Visits

Main Objective: Part 1
To determine the safety and tolerability of ascending weekly doses and estimate the MTD of oral/enteral LMI070 in infants with type 1 SMA.
Part 2
To evaluate the safety and tolerability of multiple dose weekly regimens of oral/enteral LMI070 for 12 weeks in patients with type 1 SMA.

Secondary Outcome(s)

Secondary end point(s): Secondary Endpoint Part 1
PK - D1 (Pre-dose + 1, 2, 4, 8 & 24 hours post-dose), D2, D3, D5, D8, D29, D43
Ultrasound : Baseline, D85 + EOS
Growth measurements : Screening, D1, D8-D85 + EOS
Respiratory function: Baseline, D8-D85 +EOS
CHOP-INTEND : Baseline, D36, D85 + EOS

Secondary Endpoint Part 2
PK : D1 (Pre-dose + 1, 2, 4, 8 & 24 hours post-dose), D2, D3, D5, D8, D29, D43, D57 (Pre-dose + 2, 4, 8 & 24 hours post-dose), D59, D62
Ultrasound : Baseline, D88 + EOS
Growth measurements : Screening, D1, D8-D57, D64, D71, D88 + EOS
Respiratory function - Baseline, D8-D57, D64, D71, D88 + EOS
CHOP-INTEND – Baseline, D15, D36, D57, D88 + EOS
CMAP – Baseline, D88 + EOS

Timepoint(s) of evaluation of this end point: See above

Secondary ID(s)

CLMI070X2201

2014-002053-19-DK

Source(s) of Monetary Support

Novartis Pharma services AG

Ethics review

Status: Approved
Approval date: 01/04/2015
Contact: