UMIN-CTR Clinical Trial

Basic information
Public title	Phase 1/2a, Double-blind, Placebo-controlled Study with an Open-label Extension of Ropinirole Hydrochloride Extended-Release Tablets -Explorative Assessment of the Safety, Tolerability, and Efficacy after Oral Treatment in Patients with Amyotrophic Lateral Sclerosis (ALS)-
Acronym	Phase 1/2a Study of Ropinirole Hydrochloride Extended-Release Tablets in Patients with Amyotrophic Lateral Sclerosis (ALS)
Scientific Title	Phase 1/2a, Double-blind, Placebo-controlled Study with an Open-label Extension of Ropinirole Hydrochloride Extended-Release Tablets -Explorative Assessment of the Safety, Tolerability, and Efficacy after Oral Treatment in Patients with Amyotrophic Lateral Sclerosis (ALS)-
Scientific Title:Acronym	Phase 1/2a Study of Ropinirole Hydrochloride Extended-Release Tablets in Patients with Amyotrophic Lateral Sclerosis (ALS)
Region	Japan

Condition
Condition	amyotrophic lateral sclerosis (ALS)
Classification by specialty	Neurology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	To exploratively assess the safety and tolerability of ropinirole hydrochloride, in terms of delay in the progression of ALS, after oral treatment in ALS patients.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	The kind, frequency, severity and extent of adverse events, transition of laboratory values and the percentage of discontinued cases during double blined 24 weeks.
Key secondary outcomes	After double blined 24 weeks, 1) Ratio of change in ALSFRS-R score per 4 weeks before and after treatment start 2) Change in ALSFRS-R score at 24 weeks in double-blind phase (double-blind day 1 to 24) 3) Change in ALSFRS-R score of the continuation period (final evaluation from first evaluation in continuation phase) and the whole administration period (day 1 in double-blind phase to final evaluation in continuation phase) 4) Completed Assessment of Function and Survival (CAFS) score at double-blind phase 24 weeks (day 1 to 24 weeks in double-blinded phase), continuation period (first evaluation to final evaluation in continuation phase) and whole administration period (day 1 in double-blind phase to final evaluation in continuation phase) 5) Combined evaluation by converting the following items into Z scores and adding them together ･Subscore for each ALSFRS-R domain (bulbar function, limb function, breathing function) ･ALS severity score ･Simple respiratory function test (FEV 1, FEV 6) ･Precise respiratory function test (VC, %FVC, FEV1%) ･Manual Muscle Test (MMT) score (limbs, trunk) and quantitative muscular strength ･Grip strength, pinch strength ･Modified Norris Scale (Bulbar Symptom Score) ･Tongue pressure ･Weight ･Physical activities, number of steps ･Objective muscle mass by skeletal muscle CT ･ALSAQ-40 score 6) Period until death or certain disease progression (death, inability to walk independently, abolition of one side upper limb function, tracheostomy, wearing of artificial respiratory equipment, intubation of nutrition, loss of practical conversation) 7) Period up to %FVC < 50% 8) Period until ALSFRS-R score decreased by 6 or more 9) Percentage of discontinued cases from day 1 in double-blind phase to final evaluation in continuation phase

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	NO
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Once daily ropinirole hydrochloride extended-release tablet with dose-escalation tolerable from 2mg to 16mg for double blinded 24 weeks
Interventions/Control_2	Once daily placebo tablet with dose-escalation tolerable from 2mg to 16mg for 24 weeks (Interventions)
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	80 years-old >=
Gender	Male and Female
Key inclusion criteria	(At provisional registration) (1) Patients falling under probable laboratory-supported ALS, Clinically probable ALS or Clinically definite ALS in ALS diagnostic criteria (revised El Escorial criteria by the World Federation of Neurology), and within 60 months after onset (2) Patients with severity classification of ALS (Ministry of Health, Labor and Welfare Specific Disease Research 2007.1.1) of 1 or 2 (3) Japanese patients who aged 20 to 80 years old (4) Patients with the all items in ALSFRS-R (patients with the item in writing and feeding behavior (1) on one or both sides of 2 or more points) of 2 or more points (5) Patients with percent FVC more than 70 (6) Patients who can submit written informed consent. If patients are duly capable of study consent but are unable to sign by themselves due to aggravation of disease condition, written informed consent can be obtained from a legally authorized representative who can sign on behalf of the patients after confirming the patients' agreement to study participation. (7) Patients eligible for outpatient visit (and hospitalization) during trial period (At definitive registration) (8) Patients whose change in ALSFRS-R score is between -2 to -5 during 12 weeks of observation phase (9) Patients who have not newly introduced riluzole since the start of observation phase, and who have not changed or discontinued the dose of riluzole (10) Patients who did not administered edaravone and high-dose mecobalamin (25 mg or 50 mg) since the start of observation phase (11) Patients eligible for outpatient visit (and hospitalization) during trial period
Key exclusion criteria	(1) Patients with severe diseases such as hepatic disorder, kidney disorder, heart disease, lung disease, blood disorder, metabolic disorder and whom investigators judged inappropriate for trial (2) Patients who participated in other clinical trials within 30 days prior to provisional registration (3) Patients with cancer complicated, or not more than 5 years after cure (4) Patients who have used ropinirole hydrochloride (5) Patients with family history of ALS with SOD-1 mutation or who have previously been diagnosed with ALS with SOD-1 mutations (6) Pregnant women or women who may be pregnant, lactating women (7) Patients with orthostatic hypotension with subjective symptoms (dizziness, syncope etc.) (8) Patients who have psychiatric disorders or psychiatric symptoms and are considered difficult to participate in this trial (9) Patients whom investigators judged as inappropriate for trial
Target sample size	20

Research contact person
Name of lead principal investigator	1st name Jin Middle name Last name Nakahara
Organization	Keio University Hospital
Division name	Department of Neurology
Zip code	160-0016
Address	35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
TEL	03-3353-1211
Email	nakahara@a6.keio.jp

Public contact
Name of contact person	1st name Shinichi Middle name Last name Takahashi
Organization	Keio University Hospital
Division name	Department of Neurology
Zip code	160-0016
Address	35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
TEL	03-3353-1211
Homepage URL	https://www.neurology.med.keio.ac.jp
Email	takashin@tka.att.ne.jp

Sponsor
Institute	Keio University Hospital
Institute
Department

Funding Source
Organization	Japan Agency of Medical Research and Development (AMED)
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)	K Pharma, Inc

IRB Contact (For public release)
Organization	Keio University Hospital Institutional Review Board
Address	35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
Tel	03-3353-1211
Email	keio-chiken@adst.keio.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2018 Year 11 Month 30 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	21
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2018 Year 10 Month 04 Day
Date of IRB	2018 Year 11 Month 01 Day
Anticipated trial start date	2018 Year 12 Month 05 Day
Last follow-up date	2020 Year 11 Month 30 Day
Date of closure to data entry
Date trial data considered complete	2021 Year 01 Month 08 Day
Date analysis concluded	2021 Year 03 Month 08 Day

Other
Other related information

Management information
Registered date	2018 Year 11 Month 20 Day
Last modified on	2021 Year 04 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039856