Clinical Trial Results:
The Effect of AKST4290 on Choroidal Blood Flow in Patients with Neovascular Age-Related Macular Degeneration
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Summary
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EudraCT number |
2019-002821-31 |
Trial protocol |
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Global end of trial date |
27 Apr 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Jan 2022
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First version publication date |
11 Jan 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 |
AKST4290-206
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
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 Road, Suite D, San Carlos, United States, CA 94070
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Public contact |
Department of Clinical Pharmacology, Medical University of Vienna, +43 14040029810, klin-pharmakologie@meduniwien.ac.at
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Scientific contact |
Department of Clinical Pharmacology, Medical University of Vienna, +43 14040029810, klin-pharmakologie@meduniwien.ac.at
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Sponsor organisation name |
Alkahest, Inc.
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Sponsor organisation address |
125 Shoreway Road, Suite D, San Carlos, United States, CA 94070
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Public contact |
Head of Communications, Alkahest, Inc., 001 650-801-0474,
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Scientific contact |
Head of Communications, Alkahest, Inc., 001 650-801-0474,
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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 |
06 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Apr 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Apr 2020
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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 |
To investigate the effects of a 4-week, oral b.i.d. dosing regimen of AKST4290 on choroidal blood flow (ChBF) in the contralateral eye in subjects with unilateral neovascular age-related macular degeneration (nAMD)
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Protection of trial subjects |
The study was conducted in accordance with the following:
• GCP guidelines.
• The Declaration of Helsinki including all revisions.
• Applicable national and local regulatory requirements.
The Sponsor and Principal Investigator (PI) understood that by signing the Protocol Investigator Signature Page they provided their commitment to comply with applicable Good Clinical Practice (GCP) regulation and guidances and to conduct the study in accordance with the protocol and GCP standards. In obtaining and documenting informed consent, the PI complied with the applicable regulatory requirement(s) and adhered to the International Conference on Harmonisation (ICH) guideline for GCP and the requirements in the Declaration of Helsinki.
Prior to any trial-related activity, the PI gave the subject oral and written information about the trial expressed in the appropriate local language and form that the person giving consent could read and/ or understand. The measures taken to safeguard the subject’s privacy and the protection of personnel data were described. This included information on how the identity of the subject and any recorded data was coded, stored and protected. Information was given about the person(s) who will have access to the code list data, where the list was kept and for how long and who was responsible for keeping and destroying it.
A voluntary, signed and dated Subject Information Sheet/ Informed Consent Form (SIS/ICF) was obtained from the subject prior to any trial-related activity. The subject was given a copy of the signed SIS/ICF.
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Background therapy |
The study agent was self-administered orally in the clinic under supervision of study personnel during every visit of the treatment period (Visits 2-3) after any pre-dose assessments, and then self-administered at home between study visits at dose of 400 mg b.i.d. (800 mg/day). | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Sep 2019
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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 |
Austria: 15
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Worldwide total number of subjects |
15
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EEA total number of subjects |
15
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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) |
5
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
Men and women with active CNV secondary to AMD in 1 eye, as diagnosed by a retinal specialist, with all the following characteristics and ophthalmic inclusion criteria applied to the contralateral eye (study eye), as assessed by a reader No active CNV secondary to AMD No geographic atrophy No previous treatment for AMD Ametropy < or = 6 diopter | ||||||
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Pre-assignment
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Screening details |
Males and females 50 years of age or older with unilateral active CNV secondary to AMD were eligible to participate. Body mass index (BMI) between 18 and ≤ 40 at Screening (Visit 1) Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restric | ||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Open label study
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Arms
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Arm title
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AKST4290 | ||||||
Arm description |
active treatment | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
AKST4290
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Investigational medicinal product code |
AKST4290
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The study agent was self-administered orally in the clinic under supervision of study personnel during every visit of the treatment period (Visits 2-3) after any pre-dose assessments, and then self-administered at home between study visits at dose of 400 mg b.i.d. (800 mg/day). Subjects were instructed to take the study agent at approximately the same time every day, once in the morning and once in the evening (every 12 hours). In addition, the study agent was taken approximately 1 hour before a meal or 2 hours after a meal. Training on study agent administration was conducted prior to the initial study agent administration at Visit 2.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: One subject discontinued the study and was not included in the analyzed per protocol population. |
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Primary
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Mean change in ChBF in the contralateral eye measured using LDF
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End points reporting groups
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Reporting group title |
AKST4290
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Reporting group description |
active treatment | ||
Subject analysis set title |
Primary
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Mean change in ChBF in the contralateral eye measured using LDF
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End point title |
Mean change in ChBF in the contralateral eye measured using LDF [1] | ||||||||||||
End point description |
Choroidal blood flow significantly increased over time (p = 0.037, ANOVA). A numerical increase from Visit 2 to Visit 3 as well as from Visit 3 to Visit 4 was observed in 90% of subjects. Mean (SEM) BCVA improved by 2.5 (1.3) letters at Visit 3 and by 4.4 (1.7) letters at Visit 4 in the nAMD non-study eye, while in the study eye no statistically significant change occurred. No clinically relevant changes in retinal vascular calibers, oxygen saturation or RNFLT were observed during the course of the study in neither eye. In the nAMD non-study eye, macular SD-OCT parameters such as macular thickness, central subfield thickness and macular volume trended toward improvement. Intraocular pressure decreased during the course of the study.
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End point type |
Primary
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End point timeframe |
In the study eye, a decrease in the mean central retinal arterial equivalent (CRAE) and mean central retinal venous equivalent (CRVE) from Visit 2/baseline to Visit 4/Follow-up was observed over time, which was statistically significant for CRVE
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is study with 1 arm - it means that no comparative statistical analysis |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All AEs were reviewed, documented, and reported as required at each visit, beginning at Screening.
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Adverse event reporting additional description |
TEAEs were defined as AEs that were reported or worsened on or after the start of study drug dosing and up to and including the end of the follow-up.
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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 |
21.1
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Reporting groups
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Reporting group title |
Treatment Emergent Adverse Events TEAEs
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Reporting group description |
All Subjects who received at least one dose of study drug. TEAEs were defined as AEs that were reported or worsened on or after the start of study drug dosing and up to and including the end of the follow-up. | ||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||
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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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27 Aug 2019 |
1)Added content/references to support the inclusion requirement for unilateral nAMD as a known risk factor for the development of CNV in the fellow eye
2)Removed Inclusion Criterion #4 (“Female subjects must not be pregnancy or breast feeding. Women of childbearing potential…”) and renumbered subsequent inclusion criteria.
3) Updated Exclusion Criteria as follows:
-Added Exclusion Criterion #2 Exclusion of women of childbearing potential.
- Exclusion Criterion #10f: changed to : Current, active liver disease: > 3-fold elevation of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] over upper limit of normal).
-Exclusion Criterion #10g: changed to Uncontrolled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher) despite adequate treatment during the 3 months prior to dosing.
-Exclusion Criterion #12: changed to: Planned concomitant use of CYP3A4/5 and/or P-gp substrates that have a narrow therapeutic index (e.g., digoxin, warfarin, factor Xa inhibitors).
-Exclusion Criterion #15: changed to: Planned concomitant use of organic anion transporter 1 (OAT1) and OAT3 sensitive substrates (e.g., methotrexate and pravastatin).
- Added Exclusion Criterion #17: Exclusion of patients with impaired renal function.
- Exclusion Criterion #20: changed to: Patients with clinically relevant, abnormal screening hematology, blood chemistry, or urinalysis, if the abnormality defines a significant disease as defined in other exclusion criteria (e.g., (AST) or (ALT) > 3.0-fold the upper limit of normal; total bilirubin (TBR) or prothrombin time > 1.5 times the upper limit of normal). Laboratory testing may be repeated once during the screening phase.
4) Updated statistical hypothesis.
Previously read:
• H1: Change from baseline in ChBF ≠ 0 with α1= 0.05
Now reads:
• H1: Change from baseline in ChBF ≠ 0
5) Updated content for standardization with Investigator’s Brochure. |
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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 | |||
