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Multicenter trial of SPP-004 in mitochondrial diseases (confirmatory trial) (MITO Study)

Multicenter trial of SPP-004 in mitochondrial diseases (confirmatory trial)

Akira Otake

Saitama Medical University Hospital

38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan

akira_oh@saitama-med.ac.jp

Akira Otake

Saitama Medical University Hospital

38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan

+81-49-276-1218

akira_oh@saitama-med.ac.jp

COMPLETED

June. 30, 2018

Interventional

Multicenter, randomized withdrawal, double-blind, placebo-controlled, clinical trial.

double blind

Yes

3

Japanese patients who meet all the following criteria are included in this clinical trial.
(1)Subject who meets all three clinical criteria of suspicious for Leigh syndrome as follows:
1.have progressive central nervous system symptoms
2.have symptoms of brainstem and/or basal ganglia lesions
3.Have symmetrical necrotizing lesions in brainstem and/or basal ganglia confirmed by imaging data or pathological examination*.
*bilateral and symmetric brainstem and/or basal ganglia lesions are observed,as low-density area by brain CT, or as high-intensity area by T2-weighted or FLAIR image in brain MRI, or multifocal and symmetrical lesions are confirmed at basal ganglia, thalamus, brainstem, dentate nucleus and optic nerves by pathological examination.
(2)Patients aged≧3months at the timing of IC acquisition
(3) Patients taking a food containing 5-ALA at the timing of IC acquisition and medically allowed to stop taking the food for the 28 consecutive days before starting open period
(4) Patient's legally authorized representative or subject must provide written informed consent**
**for a patient who have a competent to consent to IC must provide assent, patient needs to provide a written IC even in the case which patient's legally authorized representative provides written informed consent

Patients who meet any of the following criteria are excluded from this trial.
(1)Patients diagnosed as Vitamin B1 deficiency or organic acidemias(ex: Methylmalonic acidemia, Glutaric acidemia type1)
(2)Patients with severe cardiac function or renal function disorders
(3) Patients complicated by sepsis
(4) Patients with a history of drug allergy
(5) Patients with a history of hypersensitivity to any ingredients of the investigational drugs
(6) Patients participated in another clinical study within 12 weeks prior to the informed consent
(7) Patients with a pregnant or breast-feeding woman, or woman suspected of being pregnant
(8)Patients whom the investigator and sub-investigator considered inappropriate to participating this trial

Both

Mitochondrial disease, involved mainly central nervous system

Intervention type:DRUG Name of intervention:SPP-004 Dose form / Japanese Medical Device Nomenclature:CAPSULE Route of administration / Site of application:ORAL Dose per administration: 5-ALA HCl 25~75 and SFC 39.22~117.66 mg Dosing frequency / Frequency of use:BID Investigational drug doses are based on the body weight at observation time during the treatment period. Planned duration of intervention:Total 72w (Open period 24w, Double-blind period 48w) Intended dose regimen:Open period A capsule of each investigational drug (5-ALA HCl capsule (25 mg) and SFC capsule (39.22 mg)) is administered orally or by a feeding tube. If capsules cannot be swollen, the content should be dissolved at the time of administration. Double-blind period. Same dose in open period is administered orally or by a feeding tube. If capsules cannot be swollen, the content should be dissolved at the time of administration. Through the study treatment (open period and double-blind period), doses are based on the body weight at observation time during the treatment period. detailes of teratment arms:- Comparative intervention name:Placebo Dose form / Japanese Medical Device Nomenclature:CAPSULE Route of administration / Site of application:ORAL Dose per administration: 5-ALA HCl placebo and SFC 20.0 mg Dosing frequency / Frequency of use:BID Investigational drug doses are based on the body weight at observation time during the treatment period. Planned duration of intervention:Total 72w (Open period 24w, Double-blind period 48w) Intended dose regimen:Open period A capsule of each investigational drug (5-ALA HCl capsule (25 mg) and SFC capsule (39.22 mg)) is administered orally or by a feeding tube. If capsules cannot be swollen, the content should be dissolved at the time of administration. Double-blind period. Same dose in open period is administered orally or by a feeding tube. If capsules cannot be swollen, the content should be dissolved at the time of administration. Through the study treatment (open period and double-blind period), doses are based on the body weight at observation time during the treatment period.

The proportion of subject meeting the criteria of "insufficient" at the week of 48 in the double-blind period.

1.The proportion of subject meeting the criteria of "insufficient" at the week of 24 and 36 in the double-blind period.
2.Period (days) from starting "double-blind period" to the timing when investigator determined as "insufficient"
3.The Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Section I~III
4.NPMDS Section I,II,III, each
5.NPMDS Section I~IV, tatally
6.Blood FGF21
7.Body Weight
8.Body Height
9.Head circumference
10.Blood GDF-15
11.Respiratory chain complex enzymes activity and oxygen consumption in skin fibroblasts (if informed consent is obtained)
12.General improvement
13.MRI of Brain
14.Life prognosis
15.Period of ventilator weaning
16.Number of "stroke-like episodes" (applicable for the subject who had a history of stroke-like episodes before participation of the clinical trial)

April. 24, 2018