Clinical trial NCT04107740: C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
Official title: Multicenter, Randomized, Double-blind, Placebo-controlled, Phase IV Clinical Trial to Evaluate and Compare the Efficacy and Safety of C-Trelin OD Tab 5mg(Taltirelin Hydrate) in Patients With Ataxia Induced by Spinocerebellar Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Spinocerebellar Degeneration
Keywords: Spinocerebellar degeneration
Ataxia
Lead sponsor: HLB Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-09-27
Enrollment: 160
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the efficacy and safety of C-Trelin OD Tablet 5mg(Taltirelin Hydrate) in Multicenter, randomized, double-blind, placebo-controlled clinical trial in patients with ataxia induced by spinocerebellar degeneration.

Detailed description: Taltirelin Hydrate, an active substance of C-Trelin OD tablet 5mg, is an analogue of Thyrotropin Releasing Hormone(TRH). TRH is distributed widely in the brain, and exerts variety of central nervous system effects as well as endocrine activity such as releasing of Thyroid Stimulating Hormone(TSH) and Prolactin. Based on these actions, studies have been attempted for the treatment of various neurological diseases such as refractory epilepsy, cerebellar ataxia, amyotrophic lateral sclerosis, cerebellar ataxia and so on. C-Trelin OD tablet 5mg(Taltirelin Hydrate), an investigational product, is a commercially available drug that was approved by Ministry of Food and Drug Safety(MFDS) based on the safety and efficacy. However, the studies with this medicine were conducted before 1997, and the evaluation criteria for the efficacy was quite different from the current evaluation criteria.

In this clinical trial, K-SARA as an objective evaluation criteria validated in Korean patients is used to confirm the efficacy of C-Trelin to improve ataxia, and to prove safety by evaluating changes in clinical laboratory data and adverse events.

Eligibility criteria: Inclusion Criteria:

* Male or female patients ≥ 20 years of age
* Patients who voluntarily agreed to enroll in the study and signed an informed consent form
* Patients diagnosed with ataxia (genetic or non-genetic) due to spinocerebellar degeneration by the investigator's judgment based on the results of essential diagnostic examinations stated below.

\<Genetic ataxia\>

* Spinocerebellar ataxia(SCA)
* Friedreich's ataxia(FA)
* Other genetic ataxia

\<Non-genetic ataxia\>

* Idiopathic late onset cerebellar ataxia(ILOCA) The following examinations to diagnose ataxia (genetic or non-genetic) induced by spinocerebellar degeneration can be used, and the investigator has to diagnose by combining at least one diagnostic examination result among the following-items.
* Medical history: alcohol abuse, medication history, family history
* Genetic test: SCA 1, 2, 3, 6, 7, 8, 17, FA which is available for the patient
* Brain MRI or CT scan: abnormalities of cerebellum and pons, brain vascular disease, or brain tumors
* Retinal or optic nerve examination

Exclusion Criteria:

* Patients with bed-ridden state at the time of screening even though the patient is diagnosed with ataxia induced by spinocerebellar degeneration
* Patients with ataxia caused by stroke
* Patients with ataxia caused by cerebrovascular, alcoholic-induced or drug-induced secondary cerebellar abnormalities
* Patients with complications of other neurodegenerative diseases such as Parkinson's disease and multiple system atrophy(however, patients diagnosed with SCA 2, SCA 3, SCA 17 can be enrolled)
* Patients with malignant neoplastic disease
* Patients with kidney failure and liver failure history
* Patients with abnormalities in clinical laboratory test results as follows( Patients with liver dysfunction: Aspartate Transaminase(AST), Alanine Transaminase(ALT) \> 3 times than the upper limit of normal range(ULN), Total bilirubin \> 1.5 times than the ULN, Patients with renal dysfunction: Serum creatinine \> 1.5mg/dl, Patients with thyroid dysfunction: free T4: above or below the normal range)
* Patients with thyroid dysfunction at the time of screening(hyperthyroidism, hypothyroidism)
* Patients accompanied by lesions other than spinocerebellar degeneration from Brain MRI or CT scan
* Patients with schizophrenia, major depressive disorder
* Patients with a history of acute myocardial infarction within 2 years of the screening visit
* Patients with a history of unstable angina pectoris within 2 years of the screening visit
* Patients taking contraindicated concomitant medication( However, patients with following drugs can be enrolled only if they are administered 4 weeks before the screening visit, and the type, dosage, and volume should be kept unchanged during the clinical trial.: Parkinson's disease medicine, Anxiolytics, Antidepressants, Antiepileptics, Antipsychotics, Medicine for dysuria, Sleep inducer, β blocker)
* Patients with hypersensitivity to Taltirelin Hydrate
* Cognitive dysfunction: Korean Version of Mini-Mental State Exam(K-MMSE) ≤ 20
* Patients who are pregnant or lactating
* All childbearing females who are planning to pregnant during the clinical trial or who are not using medically reliable contraceptive methods (such as intrauterine contraceptives, condoms or diaphragms combined with spermicides) except menopaused more than 1 year from the last menstruation or had undergone surgical sterilization
* Patients participating in any other clinical trials or participated 30 days before
* Patients whom the investigator considers inappropriate for the clinical trial due to any other reasons

Primary outcomes:
measure: Changes in Korean Version of Scale for the Assessment and Rating of Ataxia(K-SARA) scores
timeFrame: 24 weeks of administration compared to the baseline
Secondary outcomes:
measure: Changes in Korean Version of Scale for the Assessment and Rating of Ataxia(K-SARA) scores
timeFrame: 4 weeks and 12 weeks of administration compared to the baseline
measure: Changes in Clinical Global Impression - Severity(CGI-S) scores
timeFrame: 4 weeks, 12 weeks, and 24 weeks of administration compared to the baseline
measure: Changes in Clinical Global Impression - Improvement(CGI-I) scores
timeFrame: 12 weeks and 24 weeks of administration compared to 4 weeks of administration
measure: Changes in Clinical Global Impression - Efficacy index(CGI-E) scores
timeFrame: 12 weeks and, 24 weeks of administration compared to 4 weeks of administration
measure: Changes in Korean Version of the Scale for Outcomes in Parkinson's Disease-Autonomic(K-SCOPA-AUT) scores
timeFrame: 24 weeks of administration compared to the baseline
measure: Changes in EQ-5D-5L scores
timeFrame: 24 weeks of administration compared to the baseline
measure: Changes in Tinetti balance test & Gait assessment scores
timeFrame: 24 weeks of administration compared to the baseline
Other outcomes:
Locations:
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Metropolitan Government Seoul National University Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul ST. Mary's Hospital
Study officials:
affiliation: Korea University Guro Hospital
name: Seong-beom Koh
role: PRINCIPAL_INVESTIGATOR
References: