Parkinson's DiseasePhase 1NCT03022799
Phase I, KM-819 in Healthy Subjects for Parkinson's Disease
A Phase 1 study testing KM-819 in people with Parkinson's Disease, run by Kainos Medicine Inc. at 1 site in South Korea.
Trial summary
This first in human, single-center, randomized, placebo-controlled, double blind, sequential group Phase 1 study in healthy subjects will be conducted to evaluate the safety, tolerability, PK, and PD following the escalation of single and multiple doses of KM-819. The study will consist of 2 parts. Read more about this study
- Who is it for?
- Ages 19 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- KM-819
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 1 siteSouth Korea
- Study dates
- Nov 2016to Nov 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
- Male subject should be 19 to 45 years old (for young adult cohorts) or over 60 years old (for elderly cohorts).
- Subject has a body mass index (BMI) range of 18.5 to 30 kg/m2 inclusive at Screening.
- Male subject and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at Screening and continuing throughout the study period and for 90 days after final study drug administration. Highly effective contraception is defined as:
- Established use of oral, injected, or implanted hormonal methods of contraception
- Placement of an intrauterine device or intrauterine system
Show all 10Show fewer
- Barrier methods of contraception: condom with spermicidal foam, gel, film, cream, suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, cream, or suppository
- Male subject must not donate sperm starting at Screening, throughout the study period and for at least 90 days after final study drug administration.
- Female subject must be over 60 years old and post-menopausal (defined as at least 1 year without any menses) prior to Screening.
- Subject agrees not to participate in another investigational study while on study treatment.
Who cannot join
- Subject has a known or suspected hypersensitivity to KM-819, or any components of the formulation(s) used.
- Subject has previously participated in a clinical study with KM-819.
- Subject has any of the liver enzymes (aspartate aminotransferase [AST], alanine transaminase [ALT], alkaline phosphatase, γ glutamyl transferase) or total bilirubin (TBIL) above the ULN. If any liver enzyme is > 1 × ULN but < 1.5 × ULN, the assessment may be repeated once during the Screening period or on check-in. If the repeated assessment is above the ULN, it is exclusionary. If the initial value is > 1.5 × ULN, it cannot be repeated and is exclusionary.
- Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, allergic rhinitis or rhino-conjunctivitis, or house dust mite allergy at time of dosing).
- Subject with a history of a suicide attempt or suicidal behavior. Any recent suicidal ideation (a level of 4 or 5) within the last 3 months, or having a positive C-SSRS at check-in (Day -1), or who is at significant risk to commit suicide, as judged by the Investigator using the C SSRS at Screening.
- Subject has/had febrile illness or symptomatic viral, bacterial (including upper respiratory infection) or fungal (non-cutaneous) infection within 1 week before site check-in.
Show all 26Show fewer
- Subject has any clinically significant abnormality following the Investigator's review of the physical examination, ECG, and protocol-defined clinical laboratory tests at Screening or site check-in.
- Subject has a mean pulse < 40 or > 90 beats per minute (bpm); mean systolic blood pressure (SBP) > 140 mmHg; or mean diastolic blood pressure (DBP) > 90 mmHg (measurements taken in triplicate after subject has been resting in the supine position for 5 minutes; pulse will be measured automatically) at Screening or check-in. If the mean pulse, mean SBP, or mean DBP is out of the range specified above, 1 additional triplicate measurement may be taken at Screening and check-in.
- Subject has a mean QTcF interval of > 430 msec (for males) and > 450 msec (for females) at Screening or check-in. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken. If this triplicate also gives an abnormal result, the subject should be excluded.
- Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease, or a family history of Long QT Syndrome.
- Subject has use of any prescribed or non-prescribed drugs (including vitamins, hormone replacement therapy, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks before study drug administration. Acetaminophen up to 2000 mg/day is allowed.
- Subject has had any use of tobacco- or nicotine-containing products within 6 months prior to Screening.
- Subject has history of consuming more than 14 units of alcoholic beverages per week within 6 months prior to Screening or has a history of alcoholism or abuse of amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates (drugs-of-abuse) within the past 2 years prior to Screening (Note: 1 unit = 355 mL of beer, 118 mL of wine, or 29 mL of spirits/hard liquor) or the subject tests positive at Screening or site admission for alcohol or drugs of-abuse.
- Subject has used any drugs-of-abuse within 3 months before check in.
- Subject has used any inducers of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to check-in.
- Subject has any significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood, or blood products within 60 days or donated plasma within 7 days before check-in.
- Subject has a positive serology test for hepatitis B surface antigen (HbsAg), anti hepatitis A virus Immunoglobulin M (HAV IgM), anti-hepatitis C virus (HCV Ab), or anti-human immunodeficiency virus (HIV Ab).
- Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 3 months or 5 half lives, whichever is longer, before the initiation of Screening.
- Subject has (recent history of) any other condition which, in the opinion of the Investigator, precludes the subject's participation in the trial.
- Subject is an employee of the Kainos Medicine, Inc. or vendors involved in the study.
- Additional Exclusion Criteria for Young Adult Subjects
- For young adult cohorts, subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the Investigator or designee.
- Exclusion Criteria for Elderly Subjects Replacement for Exclusion No. 8 above 8. Subject has a mean pulse < 50 or > 90 bpm; mean SBP > 160 mmHg; mean DBP > 100 mmHg (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically).
- Replacement for Exclusion No. 21 above 21. For elderly cohorts, subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy that is not well managed and stable, as judged by the Investigator or designee.
- Additional Exclusion Criteria 22. Elderly subject is excluded if the Glomerular Filtration Rate (calculated based on Cockcroft-Gault formula) is < 60 mL/min/1.73 m2.
- 23. Clinically significant abnormal findings in the lumbar X-ray examination (only for elder subjects for MAD study).
Trial locations and contacts
1 site in 1 country.
South Korea1 site
CHA Bundang Medical Center, CHA University
Seongnam-si, Gyeonggi-do, 13496
About this study
Official title: A First in Human, Randomized, Double-blind, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Following Single and Multiple Oral Doses of KM-819 in Healthy Young Adult and Elderly Subjects
This first in human, single-center, randomized, placebo-controlled, double blind, sequential group Phase 1 study in healthy subjects will be conducted to evaluate the safety, tolerability, PK, and PD following the escalation of single and multiple doses of KM-819.
The study will consist of 2 parts. In Part A, up to 5 cohorts of young adult male subjects, and 1 single dose cohort of elderly male or post menopausal female subjects will receive escalating single doses of KM-819. In Part B, up to 4 cohorts of healthy young adult male subjects and 1 multiple dose cohort of elderly male or post menopausal female subjects will receive escalating multiple doses of KM-819. Part B will be conducted after completion of all cohorts of young adult male subjects in Part A.
Read more
Dose escalation to the next level will be determined using safety, tolerability, and PK data of the previous cohort.
Part A, Single Ascending Dose (SAD) Up to 40 healthy young adult male subjects and 8 healthy elderly male or post menopausal female subjects will be enrolled and randomized to receive either KM-819 or placebo.
Each of the 5 dose escalation cohorts consists of 8 healthy young adult male subjects; 6 subjects will receive 10, 30, 100, 200, or 400 mg of KM-819 and 2 subjects will receive placebo. In each single dose cohort, dosing of subjects will be sentinel, i.e., 2 subjects will be dosed on the first day (1 subject will receive active treatment and 1 subject will receive placebo) and the remaining 6 subjects will be dosed at least 24 hours after the first 2 subjects.
Cohorts will be dosed sequentially with escalating doses. Eight elderly male or post-menopausal female subjects will be enrolled into an additional cohort; 6 subjects will receive 200 mg KM-819 and 2 subjects will receive placebo.
Part A consists of a Screening period of up to 28 days, and a 3 day Confinement period when subjects are hospitalized for study activities. Subjects are required to return for outpatient visits on Day 4, 7 and for the Follow up Visit on Day 14.
Part B, Multiple Ascending Dose (MAD) Up to 32 healthy young adult male subjects and 8 healthy elderly male or post menopausal female subjects will be enrolled and randomized to receive either KM-819 or placebo.
Each of the 4 dose escalation cohorts consists of 8 healthy young adult male subjects; 6 subjects will receive 30, 100, 200, or 400 mg of KM-819 once a day (QD) for 7 days and 2 subjects will receive placebo. Cohorts will be dosed sequentially with escalating doses.
Eight elderly male or post-menopausal female subjects will be enrolled into an additional cohort; 6 subjects will receive 200 mg KM-819 QD for 7 days and 2 subjects will receive placebo.
- Conditions
- Parkinson's Disease
- Being tested
- KM-819, Placebo
- Keywords
- FAF1, Fas (TNFRSF6)-associated factor 1, FAF1 inhibitor, KM-819
- Medical subject headings
- Parkinson Disease, Autoimmune Lymphoproliferative Syndrome, Type IA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KM-819Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| KM-819 | Experimental | Each cohort consists of 8 subjects; 6 subjects will receive planned dose of KM-819 and 2 subjects will receive placebo. Receives: Drug: KM-819 |
| Placebo | Placebo comparator | Each cohort consists of 8 subjects; 6 subjects will receive planned dose of KM-819 and 2 subjects will receive placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
All AEs will be coded using the latest available version 19.1 of the Medical Dictionary for Regulatory Activities (MedDRA).
A treatment-emergent adverse event (TEAE) is defined as an AE that begins or that worsens in severity after at least one dose of the study drug has been administered.
Measured: From screening (Day-28 to Day -2), Day -1 to Day 4, Day 7, and follow-up visit Day 14.
Secondary outcomes (19)
Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile)
To evaluate Cmax of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part A: Day1 to Day 4. Part B: Day-1 to Day 8
Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part A:Day 1 to 4; Part B: Day 1 to Day 8
t½ (Apparent Terminal Elimination Half Life)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects. To evaluate the PK and PD of single and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part A: Day 1 to Day 4. Part B: Day1 to Day 8
Tlag (Lag Time)
To evaluate the T lag of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part A: Day1 to Day 4. Part B: Day 1 to Day 8
AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration)
To evaluate AUClast of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part A: Day 1 to 4; Part B: Day 1 to Day 8
AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity)
To evaluate AUCinf of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male-subjects.
Measured: Part A: Day 1 to 4; Part B: Day 1 to Day 8
%AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast)
To evaluate %AUCex of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part A: Day 1 to 4; Part B: Day 1 to Day 8
CL/F (Apparent Oral Clearance)
To evaluate the CL/F of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part A: Day 1 to 4; Part B: Day 1 to Day 8
Vz/F (Apparent Volume of Distribution)
To evaluate Vz/F of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects.
Measured: Part A: Day 1 to 4; Part B: Day 1 to Day 8
AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects.
Measured: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Rac(AUC) (Observed Accumulation by AUC) (Part B)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects.
Measured: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Rac (Cmax) (Observed Accumulation by Cmax) (Part B)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
AUCtau_D (AUCtau Divided by Dose) (Part B)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Change From Baseline for Bond and Lader Visual Analogue Scale (VAS)
The Bond-Lader Visual Analogue Scales (VAS) will be analyzed using 3 factor scores: alertness, contentedness, and calmness. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered. Baseline is defined as the last available recording prior to dosing on Day 1.
- Alertness (Range 0 to 100, the higher scores indicated more alertness)
- Mood (Range 0 to 100, where higher scores indicated elevated mood)
- Calmness (Range 0 to 100, where higher scores indicated more calmness).
Measured: At Day 1 (3 hours post dose), Day2, Day 3, Day 4, and Day 8.
Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV)
The K-WAIS-IV consists of an assessment of the cognitive ability using a core battery of 10 unique subtests (Block Design, Similarities, Digit Span, Matrix Reasoning, Vocabulary, Arithmetic, Symbol Search, Visual Puzzles, Information, and Coding) that focus on four specific domains of intelligence: verbal comprehension, perceptual reasoning, working memory, and processing speed. The Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index (standard scores: mean=100, standard deviation=15) that are all based on a number of core and supplemental subtests (scaled scores: mean=15, standard deviation=3) that provide pertinent clinical information and flexibility in implementation. The higher values represent a better outcome.
Measured: Part A: Day 1; Part B: Day 7
Alpha Synuclein Oligomer in Plasma and CSF (Part B)
To evaluate Alpha synuclein oligomer in plasma and CSF of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: Plasma - Part B: Day 7 (at 1 hour after last dosing) / CSF - Part B: Day 7 (at 1 hour after last dosing)
Change From Baseline Total Tau in CSF (Part B)
To evaluate Total Tau in CSF of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: CSF - Part B: Day 1 (at -120 minutes to 0 minute prior to the first dosing) and on Day 7 (at 1 hour after last dosing)
Change From Baseline Phospho-Tau in CSF (Part B)
To evaluate Phospho-Tau of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Measured: CSF - Part B: Day 1 (at -120 minutes to 0 minute prior to the first dosing) and on Day 7 (at 1 hour after last dosing)
Ratio of CSF Concentration/Plasma Cmax (Part B)
Ratio of CSF concentration/Plasma Cmax
Measured: Plasma - Part B: Day 7 (at 1 hour after last dosing) / CSF - Part B: on Day 7 (at 1 hour after last dosing)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2017 (estimated)
- Study startNov 2016
- Primary completionSep 2017
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kainos Medicine Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jae Moon Lee, PhD, Study director, Kainos Medicine Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03022799
- Sponsor's protocol ID
- KMCP-819-K101
- Status last verified
- Mar 2020
- First submitted
- 27 Dec 2016
- Last updated
- 13 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Individual identifiable personal information will not be shared. All individuals will be coded by a 4-digit study code.
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First in Human, Randomized, Double-blind, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Following Single and Multiple Oral Doses of KM-819 in Healthy Young Adult and Elderly Subjects
- ClinicalTrials.gov ID
- NCT03022799
- Acronym / sponsor ID
- KMCP-819-K101
- Conditions
- Parkinson's Disease
- Keywords
- FAF1, Fas (TNFRSF6)-associated factor 1, FAF1 inhibitor, KM-819
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Kainos Medicine Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2016 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 18 Jan 2017 (estimated)
- Results
- Posted 13 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This first in human, single-center, randomized, placebo-controlled, double blind, sequential group Phase 1 study in healthy subjects will be conducted to evaluate the safety, tolerability, PK, and PD following the escalation of single and multiple doses of KM-819.
The study will consist of 2 parts. In Part A, up to 5 cohorts of young adult male subjects, and 1 single dose cohort of elderly male or post menopausal female subjects will receive escalating single doses of KM-819. In Part B, up to 4 cohorts of healthy young adult male subjects and 1 multiple dose cohort of elderly male or post menopausal female subjects will receive escalating multiple doses of KM-819. Part B will be conducted after completion of all cohorts of young adult male subjects in Part A.
Dose escalation to the next level will be determined using safety, tolerability, and PK data of the previous cohort.
Part A, Single Ascending Dose (SAD) Up to 40 healthy young adult male subjects and 8 healthy elderly male or post menopausal female subjects will be enrolled and randomized to receive either KM-819 or placebo.
Each of the 5 dose escalation cohorts consists of 8 healthy young adult male subjects; 6 subjects will receive 10, 30, 100, 200, or 400 mg of KM-819 and 2 subjects will receive placebo. In each single dose cohort, dosing of subjects will be sentinel, i.e., 2 subjects will be dosed on the first day (1 subject will receive active treatment and 1 subject will receive placebo) and the remaining 6 subjects will be dosed at least 24 hours after the first 2 subjects.
Cohorts will be dosed sequentially with escalating doses. Eight elderly male or post-menopausal female subjects will be enrolled into an additional cohort; 6 subjects will receive 200 mg KM-819 and 2 subjects will receive placebo.
Part A consists of a Screening period of up to 28 days, and a 3 day Confinement period when subjects are hospitalized for study activities. Subjects are required to return for outpatient visits on Day 4, 7 and for the Follow up Visit on Day 14.
Part B, Multiple Ascending Dose (MAD) Up to 32 healthy young adult male subjects and 8 healthy elderly male or post menopausal female subjects will be enrolled and randomized to receive either KM-819 or placebo.
Each of the 4 dose escalation cohorts consists of 8 healthy young adult male subjects; 6 subjects will receive 30, 100, 200, or 400 mg of KM-819 once a day (QD) for 7 days and 2 subjects will receive placebo. Cohorts will be dosed sequentially with escalating doses.
Eight elderly male or post-menopausal female subjects will be enrolled into an additional cohort; 6 subjects will receive 200 mg KM-819 QD for 7 days and 2 subjects will receive placebo.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| KM-819 | Experimental | Drug: KM-819Each cohort consists of 8 subjects; 6 subjects will receive planned dose of KM-819 and 2 subjects will receive placebo. |
| Placebo | Placebo comparator | Drug: PlaceboEach cohort consists of 8 subjects; 6 subjects will receive planned dose of KM-819 and 2 subjects will receive placebo. |
Who may qualify
- Ages
- 19 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
- Male subject should be 19 to 45 years old (for young adult cohorts) or over 60 years old (for elderly cohorts).
- Subject has a body mass index (BMI) range of 18.5 to 30 kg/m2 inclusive at Screening.
- Male subject and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at Screening and continuing throughout the study period and for 90 days after final study drug administration. Highly effective contraception is defined as:
- Male subject must not donate sperm starting at Screening, throughout the study period and for at least 90 days after final study drug administration.
Key exclusion criteria (26 listed)
- Subject has a known or suspected hypersensitivity to KM-819, or any components of the formulation(s) used.
- Subject has previously participated in a clinical study with KM-819.
- Subject has any of the liver enzymes (aspartate aminotransferase [AST], alanine transaminase [ALT], alkaline phosphatase, γ glutamyl transferase) or total bilirubin (TBIL) above the ULN. If any liver enzyme is > 1 × ULN but < 1.5 × ULN, the assessment may be repeated once during the Screening period or on check-in. If the repeated assessment is above the ULN, it is exclusionary. If the initial value is > 1.5 × ULN, it cannot be repeated and is exclusionary.
- Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, allergic rhinitis or rhino-conjunctivitis, or house dust mite allergy at time of dosing).
- Subject with a history of a suicide attempt or suicidal behavior. Any recent suicidal ideation (a level of 4 or 5) within the last 3 months, or having a positive C-SSRS at check-in (Day -1), or who is at significant risk to commit suicide, as judged by the Investigator using the C SSRS at Screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KM-819 | Drug | KM-819 |
| Placebo | Drug | Placebo |
Primary outcome
Number of Participants With Adverse Events
Time frame: From screening (Day-28 to Day -2), Day -1 to Day 4, Day 7, and follow-up visit Day 14.
All AEs will be coded using the latest available version 19.1 of the Medical Dictionary for Regulatory Activities (MedDRA). A treatment-emergent adverse event (TEAE) is defined as an AE that begins or that worsens in severity after at least one dose of the study drug has been administered.
19 secondary outcomes
Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile)
Time frame: Part A: Day1 to Day 4. Part B: Day-1 to Day 8
Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile)
Time frame: Part A:Day 1 to 4; Part B: Day 1 to Day 8
t½ (Apparent Terminal Elimination Half Life)
Time frame: Part A: Day 1 to Day 4. Part B: Day1 to Day 8
Tlag (Lag Time)
Time frame: Part A: Day1 to Day 4. Part B: Day 1 to Day 8
AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration)
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity)
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
%AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast)
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
CL/F (Apparent Oral Clearance)
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
Vz/F (Apparent Volume of Distribution)
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B)
Time frame: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Rac(AUC) (Observed Accumulation by AUC) (Part B)
Time frame: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Rac (Cmax) (Observed Accumulation by Cmax) (Part B)
Time frame: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
AUCtau_D (AUCtau Divided by Dose) (Part B)
Time frame: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Change From Baseline for Bond and Lader Visual Analogue Scale (VAS)
Time frame: At Day 1 (3 hours post dose), Day2, Day 3, Day 4, and Day 8.
Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV)
Time frame: Part A: Day 1; Part B: Day 7
Alpha Synuclein Oligomer in Plasma and CSF (Part B)
Time frame: Plasma - Part B: Day 7 (at 1 hour after last dosing) / CSF - Part B: Day 7 (at 1 hour after last dosing)
Change From Baseline Total Tau in CSF (Part B)
Time frame: CSF - Part B: Day 1 (at -120 minutes to 0 minute prior to the first dosing) and on Day 7 (at 1 hour after last dosing)
Change From Baseline Phospho-Tau in CSF (Part B)
Time frame: CSF - Part B: Day 1 (at -120 minutes to 0 minute prior to the first dosing) and on Day 7 (at 1 hour after last dosing)
Ratio of CSF Concentration/Plasma Cmax (Part B)
Time frame: Plasma - Part B: Day 7 (at 1 hour after last dosing) / CSF - Part B: on Day 7 (at 1 hour after last dosing)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. Individual identifiable personal information will not be shared. All individuals will be coded by a 4-digit study code.
Related trials for Parkinson's Disease
Enrolling by invitationObservational study
Early Molecular Biomarkers for Differentiating Parkinsonian Syndromes
PARKINSON DISEASE (Disorder), Atypical Parkinsonism
Active, not recruitingPhase 1/2
Clinical Safety and Efficacy of Umbilical Cord Mesenchymal Stromal Cells-derived Exosomes in Patients With Parkinson's Disease
Parkinson Disease (PD)
Active, not recruitingObservational study
Adaptive DBS to Offset STN Dysregulation During Exercise in PD
Parkinson Disease
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jae Moon Lee, PhD study director
Kainos Medicine Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KM-819 in people with Parkinson's Disease, run by Kainos Medicine Inc. at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: From screening (Day-28 to Day -2), Day -1 to Day 4, Day 7, and follow-up visit Day 14.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2020.