UMIN-CTR Clinical Trial

Basic information
Public title	A Phase II, Randomised, Double-Blind, Placebo-Controlled Study Followed by a Continuing Open Label Study, to Verify the Efficacy and Safty of Intrathecal Administration of KP-100IT using NP022 in Subjects with Amyotrophic Lateral Sclerosis (ALS)
Acronym	A Phase II, Randomised, Double-Blind, Placebo-Controlled Study Followed by a Continuing Open Label Study, to Verify the Efficacy and Safty of Intrathecal Administration of KP-100IT using NP022 in Subjects with Amyotrophic Lateral Sclerosis (ALS)
Scientific Title	A Phase II, Randomised, Double-Blind, Placebo-Controlled Study Followed by a Continuing Open Label Study, to Verify the Efficacy and Safty of Intrathecal Administration of KP-100IT using NP022 in Subjects with Amyotrophic Lateral Sclerosis (ALS)
Scientific Title:Acronym	A Phase II, Randomised, Double-Blind, Placebo-Controlled Study Followed by a Continuing Open Label Study, to Verify the Efficacy and Safty of Intrathecal Administration of KP-100IT using NP022 in Subjects with Amyotrophic Lateral Sclerosis (ALS)
Region	Japan

Condition
Condition	Amyotrophic Lateral Sclerosis (ALS)
Classification by specialty	Neurology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To Verify the Efficacy to Delay Disease Progression of ALS by Intrathecal Repeated Administration of KP-100IT using NP022 in Subjects with Amyotrophic Lateral Sclerosis (ALS)
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Difference in the change of ALSFRS-R score (delta ALSFRS-R) during the 24 weeks-double blind period, starting from the time point before initial administration (implantation period) to the point of 24 weeks observation between Placebo and KP-100IT groups
Key secondary outcomes	Comparison of changing rate in ALSFRS-R score per 30 days between before and after the treatment Difference in the following items between at the time before initial administration (implantation period) and at the point of 24 weeks in administration/observation period ALSFRS-R sub score of each domain (bulbar function, extremities function, respiratory function), %FVC, MMT Score (extremities, neck muscles), Modified Norris Scale (extremities symptom score, bulbar symptom score, total scores), weight, grip strength, ALSAQ40 score, ALS severity classification Time to death or to a defined event (death, inability of independent ambulation, loss of unilateral upper limb function, tracheostomy, ventilated, tube feeding, loss of vocal conversation) Time reaching to the state of %FVC<50% (time length until %FVC decreases to <50%) Time length until ALSFRS-R score decreases by 6 points or more [score change (delta ALSFRS-R) from initial administration (implantation period) is -6 or less] Discontinuance rate after initial administration Safety of repeated administration of KP-100IT for a long period Safety and defects of NP022 when KP-100IT is intrathecally administered repeatedly for a long period

Base
Study type	Interventional

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

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine Device,equipment
Interventions/Control_1	24 weeks repeated intrathecal administration of KP-100IT at 2 mg (once per 2 weeks, double blind period)
Interventions/Control_2	24 weeks repeated intrathecal administration of placebo (once per 2 weeks, double blind period)
Interventions/Control_3	24 weeks repeated-intrathecal administration of KP-100IT at 2 mg (once per 2 weeks, continuing open label period)
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	70 years-old >=
Gender	Male and Female
Key inclusion criteria	[Interim Registration] Subjects who are - Diagnosed as "Clinically Definite ALS", "Clinically Probable ALS" or "Clinically Possible-Laboratory-supported ALS" according to the El Escorial revised Criteria, and within 30 months after onset of the disease (at the time of obtaining informed consent (IC)) - Classified as class 1 or 2 in ALS severity classification - Aged 20 or older and 70 or younger at the time of obtaining informed consent (IC) - With 2 points or more in every question of ALSFRS-R (in writing and eating action (1), both sides should be 2 points or more) - %FVC is not less than 70 - Two points or more in every question of bulbar symptom scale in the modified Norris Scale - Agreed by written IC for entry in the trial [Registration] Subjects who - meet the following criteria in addition to the inclusion criteria for the interim registration - Change in ALSFRS-R score during 12 weeks-preobsevation period is within the range between -1 and -3 - Can come into hospital by the day before the day of NP022 implantation and can stay hospital until the next day of the first administration
Key exclusion criteria	Subjects who - Have serious hepatic disorder, renal disorder, cardiovascular disease, pulmonary disorder, hematological disorder or metabolism disorder, and are judged by the investigators to be improper for entry in the trial - With HbA1c (NGSP scale) of 6.5% or higher at the check of screening period - Participated in clinical trials of INDs or clinical studies receiving treatment within a month before interim registration (30 days including interim registration date) - With the following diseases or symptoms which might affect safety: malignant tumor, intrathecal infection, intrathecal tumor, proliferative retinopathy, depressed respiratory function (less than 70 of %FVC) - Have a medical history of cancer - Have a drug allergy - Newly started taking of Riluzole after obtaining IC - Participated in the Phase I Trial (protocol KP-100-ND001) - With allergy to antibiotics or intolerance for devices implantation - With allergy to the material of NP022, and including suspected above - Have an anatomical difficulty in intrathecal catheterization - Have an abnormality other than ALS in the spinal cord, the spine, the subarachnoidal cavity, or cerebrospinal fluid circulation, and are judged to be inappropriate for this trial - With infectious diseases requiring a systemic therapy, meningitis, sepsis, bacteremia, peritonitis, or cutaneous infection, and including suspected above - With bleeding diathesis - With impaired coagulation-fibrinolysis, or taking anticoagulant or antiplatelet drugs - Diagnosed as dementia - Mentally impaired or have psychiatric disorders, and are judged to be inappropriate for the trial - Pregnant (including suspected), nursing, wishing to become pregnant, or unable to prevent conception during the trial period using contraceptive methods - Judged by the investigators to be inappropriate for any reason
Target sample size	48

Research contact person
Name of lead principal investigator	1st name Masashi Middle name Last name Aoki, MD, PhD
Organization	Tohoku University Graduate School of Medicine
Division name	Department of Neurology
Zip code	980-8574
Address	1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
TEL	022-717-7000
Email	admin@neurol.med.tohoku.ac.jp

Public contact
Name of contact person	1st name Hitoshi Middle name Last name Warita, MD, PhD
Organization	Tohoku University Hospital
Division name	Department of Neurology
Zip code	9808574
Address	1-1 Seiryo-machi, Aoba-ku, Sendai, Japan
TEL	022-717-7000
Homepage URL	http://www.neurol.med.tohoku.ac.jp/
Email	warita@tohoku.ac.jp

Sponsor
Institute	Tohoku University
Institute
Department

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

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

IRB Contact (For public release)
Organization	Tohoku University Hospital Institutional Review Board
Address	1-1 Sseiryo, Aoba-ku, Sendai, Miyagi
Tel	022-717-7056
Email	chiken@grp.tohoku.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	2016.4.28., 3回

Institutions
Institutions	東北大学病院（宮城県）、大阪大学医学部附属病院（大阪府）

Other administrative information
Date of disclosure of the study information	2016 Year 05 Month 13 Day

Related information
URL releasing protocol	http://www.neurol.med.tohoku.ac.jp/cgi-bin/dayori/webdir/99.html
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
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	2016 Year 02 Month 26 Day
Date of IRB	2016 Year 03 Month 28 Day
Anticipated trial start date	2016 Year 06 Month 01 Day
Last follow-up date	2021 Year 12 Month 08 Day
Date of closure to data entry	2022 Year 04 Month 15 Day
Date trial data considered complete	2022 Year 05 Month 23 Day
Date analysis concluded	2022 Year 08 Month 10 Day

Other
Other related information

Management information
Registered date	2016 Year 04 Month 25 Day
Last modified on	2022 Year 05 Month 09 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025102