Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AKST4290 in Subjects with Parkinson's Disease on Stable Dopaminergic Treatment
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Summary
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EudraCT number |
2019-001657-42 |
Trial protocol |
DE SK |
Global end of trial date |
10 Mar 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jul 2022
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First version publication date |
29 Jul 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AKST4290-211
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04369430 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Alkahest, Inc.
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Sponsor organisation address |
125 Shoreway Rd, Suite D, San Carlos, United States, 94070
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Public contact |
Regulatory Affairs, Alkahest, Inc., +1 6508010474, trials@alkahest.com
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Scientific contact |
Clinical Development, Alkahest, Inc., +1 6508010474, trials@alkahest.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Apr 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Feb 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Mar 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This study will evaluate the efficacy and safety of AKST4290 in subjects with Parkinson’s Disease who are currently on stable dopaminergic treatment.
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Protection of trial subjects |
Prior to initiation of any study-specific procedures, subjects received a copy of the Informed Consent Form (ICF) that summarized, in non-technical terms, the purpose of the study, the procedures to be carried out, and the potential hazards. The PI or authorized representative explained the nature of the study to the subjects, in non-technical terms, and answered all questions regarding the study. Subjects reviewed, signed, and dated the ICF. Subjects received a copy of the fully signed ICF. The subject was given adequate time to read the ICF and the opportunity to ask questions and consider the statement before signing and dating the form. They were also given a copy of the signed document. No subject entered the study before informed consent or assent with parental consent was obtained. The date the ICF was signed was recorded, and the investigator retained a copy of the signed ICF.
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Background therapy |
Stable dopaminergic therapy (e.g., levodopa, dopamine agonists, monoamine oxidase inhibitors, catechol-O-methyl transferase inhibitors, amantadine), for a least 8 weeks prior to enrollment and remain on stable dose during the 12-week treatment period. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Jan 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 14
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Country: Number of subjects enrolled |
Poland: 32
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Country: Number of subjects enrolled |
Slovakia: 29
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Country: Number of subjects enrolled |
Estonia: 5
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Country: Number of subjects enrolled |
Germany: 27
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Worldwide total number of subjects |
107
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EEA total number of subjects |
93
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
62
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From 65 to 84 years |
45
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85 years and over |
0
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Recruitment
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Recruitment details |
The study enrolled 107 subjects, randomized in a 1:1 ratio to active treatment in Arm 1 (52 subjects) or placebo in Arm 2 (55 subjects). The recruitment occurred at 22 clinical sites in United States, Germany, Estonia, Poland, and Slovakia from 16-Jan-2020 (First Patient First Visit - FPFV) to 5-Nov-2020 (Last Patient First Visit - LPFV). | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
130 subjects were screened for the study. Eligible subjects were randomly assigned in a 1:1 ratio to AKST4290 or placebo. Study treatment was administered to 52 subjects in AKST4290 arm and 55 subjects in placebo arm. There were 3 subjects who were randomized but not treated. | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Monitor, Subject, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||
Blinding implementation details |
1:1 ratio AKST4290 (Active):Placebo
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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AKST4290 | ||||||||||||||||||||||||||||||
Arm description |
Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
AKST4290
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
AKST4290 is a small molecule antagonist of human CCR3. The study treatment was self-administered orally twice daily (b.i.d.) (2 × 200 mg per dose), approximately 12 hours apart, for a total daily dose of 800 mg. Subjects received the study treatment for a total of 12 weeks, followed by 4 weeks of follow-up.
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm description |
Subjects will receive placebo, 400 mg twice daily, for 12 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo was self-administered orally twice daily (b.i.d.) (2 × 200 mg per dose), approximately 12 hours apart, for a total daily dose of 800 mg. Subjects received placebo for a total of 12 weeks, followed by 4 weeks of follow-up.
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Baseline characteristics reporting groups
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Reporting group title |
AKST4290
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Reporting group description |
Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects will receive placebo, 400 mg twice daily, for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
AKST4290
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Reporting group description |
Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects will receive placebo, 400 mg twice daily, for 12 weeks. | ||
Subject analysis set title |
Modified Intent-to-Treat/Evaluable
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Subjects with non-missing Baseline and primary endpoint data
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects who received at least one dose of the study medication
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End point title |
Change in Motor Function During Levodopa Withdrawal | ||||||||||||||||||||
End point description |
Change from Baseline in motor function during the practically defined off-medication state, defined as at least 12 hours off levodopa, at Week 12 as measured by Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Part 3 Motor Examination (33 scores based on 18 questions with several right, left, or both body distribution scores). Each Parkinsonian sign or symptom is rated on a 5‐point Likert‐type scale (ranging from 0 to 4), with higher scores indicating more severe impairment. The minimum score on the MDS-UPDRS Part 3 is 0 and the maximum is 132.
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End point type |
Primary
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End point timeframe |
Baseline to 12 weeks
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Statistical analysis title |
Change from baseline at Week 12 (Day 84) | ||||||||||||||||||||
Statistical analysis description |
The main analysis for the primary efficacy variable will be analyzed using modified Intent-to-Treat subjects.
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Comparison groups |
AKST4290 v Placebo
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Number of subjects included in analysis |
90
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
= 0.1 | ||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||
Confidence interval |
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95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
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upper limit |
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Variability estimate |
Standard error of the mean
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to Week 14
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
AKST4290
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Reporting group description |
Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects will receive placebo, twice daily, for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Apr 2019 |
Expanded to Germany and updated US site number, update eligibility criteria to provide clarity and reflect global regulatory requirements, update schedule of events |
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17 May 2019 |
Provide justification of dose selection, add exploratory endpoint and assessment |
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24 Jul 2019 |
Expand geographic range to support timely recruitment and additional geographic representation, update eligibility criteria to aid investigators in determining eligibility and reflect global regulatory requirements |
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02 Dec 2019 |
Update eligibility criteria and prohibited medications based on findings from a clinical drug-drug interaction study |
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06 Jan 2020 |
Germany and US version of amendment 3.0 |
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22 May 2020 |
Update content to provide clarification on the order of assessments, add new optional sample collections, and new content added to account for potential protocol deviations related to COVID-19. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
