Myoclonus Epilepsies, ProgressivePhase 1AUT022201NCT05873062
Safety, Blood Levels and Effects of AUT00201 in Patients With MEAK
A Phase 1 study testing AUT00201 in people with Myoclonus Epilepsies, Progressive, run by Autifony Therapeutics Limited at 1 site in United States.
Trial summary
A randomized, double-blind, placebo-controlled, crossover study to assess the safety, tolerability, and pharmacokinetics of single doses of AUT00201 at 100 mg or matching placebo in patients with myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myoclonus Epilepsies, Progressive
- What is being tested?
- AUT00201
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 12 May 2023to 1 May 2024
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients aged 18 years or older at time of consenting.
- Diagnosed with MEAK, based on documented genetic evidence of the presence of the KCNC1 (c.959G>A; p.Arg320His) variant.
- If take anticonvulsants, must be on a stable anticonvulsant regiment for at least 30 days prior to Visit 1 and anticipated to remain stable throughout the study or if not on an anticonvulsant regimen, must be stable in regards to seizures for at least 30 days prior to Visit 1 and anticipated to remain stable throughout the study.
- Must be able to participate and willing to give written informed consent. If patient is unable to provide written informed consent, a legally authorized representative can sign on their behalf.
- Must be willing to perform study assessments and comply with the study protocol.
- If the patient is dependent on a caregiver and/or will need assistance either travelling to the site, whilst attending clinic visits and/or helping to document study assessment responses provided by the patient (eg, questionnaires administered on a tablet device), they must have an identified caregiver, considered reliable by the Investigator, to provide support to the patient for the duration of the study. The caregiver must be willing and able to provide support to the patient and, if required, stay for the duration of the study.
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- Medically stable based on Investigator's judgement for at least 90 days prior to Visit 1.
- Women of childbearing potential must have a negative urine pregnancy test on Visit 2.
- If a vagal nerve stimulator is used, it must be implanted at least 150 days before Day. -1, and parameters must be stable for at least 30 days before Visit 1 and expected to remain stable throughout the study.
- If a ketogenic diet is followed, it must be stable for at least 30 days before Visit 1 and expected to remain stable throughout the study.
- Willing to comply with contraceptive requirements.
- Able to speak, read and understand English at a fluent level
Who cannot join
- Known pathogenic mutation in another gene that causes epilepsy or a different mutation in the KCNC1 gene than the c.959G>A variant.
- Clinically significant metabolic, hepatic, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder.
- Clinically significant abnormal vital signs or laboratory test results.
- Hypersensitivity to AUT00201 or any of the excipients.
- Any medical condition or other factors, as judged by the Investigator, which may interfere with the patient's participation in this study and/or compromise the patient's ability to safely complete the study.
- Known to abuse drugs or those who test positive on urine screen for drugs of abuse will be excluded based on Investigator's judgement.
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- Positive hepatitis B surface antigen or hepatitis C antibody.
- Clinically significant abnormality on the 12-lead electrocardiogram.
- Having received an investigational product 90 days prior to Visit 1.
- Currently using felbamate <1 year prior to Visit 1, or any evidence of ongoing hepatic or bone marrow dysfunction associated with current/prior felbamate treatment. Patients who are currently using felbamate for >1 year prior to Visit 1 and have no evidence of ongoing hepatic or bone marrow dysfunction associated with felbamate treatment are allowed.
- Currently using vigabatrin and having received vigabatrin for <2 years prior to Visit 1.
- Suicidal ideation with some intent to act within 6 months prior to Visit 1 based upon response in the Columbia-Suicide Severity Rating Scale (positive response to questions 4 or 5 of the suicidal ideation section) and as judged by the Investigator as having a significant impact on trial participation or patient safety. History of suicidal behavior within 1 year prior to Visit 1.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania, Penn Epilepsy Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Crossover Study of the Effects of Single Doses of AUT00201 in Patients With Myoclonus Epilepsy and Ataxia Due to Potassium (K+) Channel Mutation (MEAK)
A randomized, double-blind, placebo-controlled, crossover study to assess the safety, tolerability, and pharmacokinetics of single doses of AUT00201 at 100 mg or matching placebo in patients with myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK).
Read the detailed description
6 to 10 patients aged 18 years and older, diagnosed with MEAK will be enrolled in the study. Patients will be administered a single dose of AUT00201 and matching placebo in a crossover design. The study is comprised of an outpatient screening and procedure orientation followed by approximately 5 days of an inpatient stay at a clinical research unit. After screening/orientation (Visit 1), and baseline assessments (Visit 2), patients will be administered a single dose of 100 mg of AUT00201 or matching placebo the morning of Visit 3. PK assessments will be done at Visits 3, 4, 5, and 6 from predose and up to 27 hours postdose. Visit 4 will be a washout day for patients. At Visit 5 patients will be administered the crossover treatment. At Visit 6 patients will be discharged from the unit. Safety and tolerability assessments will be conducted throughout. PD parameters will also be assessed. Patients will be followed up by telephone 14 days after discharge.
- Conditions
- Myoclonus Epilepsies, Progressive
- Being tested
- AUT00201, Placebo
- Keywords
- MEAK, EPM7
- Medical subject headings
- Myoclonic Epilepsies, Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AUT00201Drug
Single oral dose
PlaceboDrug
Single oral dose
| Study group | Role | What they receive |
|---|---|---|
| Experimental: AUT00201 | Experimental | Single dose (oral, capsule) of AUT00201 Receives: Drug: AUT00201 |
| Experimental: Placebo | Placebo comparator | Single dose matching placebo oral capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Related Adverse Events After Single Dose Treatment of AUT00201 Compared to Placebo
Measured: 19 Days
Secondary outcomes (6)
Change From Baseline in Cortical Inhibition; as Measured by Paired-pulse Transcranial Magnetic Stimulation (ppTMS) at Short Interval Cortical Inhibition (SICI) Inter-stimulus-intervals (ISI): the Outcome is the Average %-Inhibition at SICI 2.5 and 3ms ISI
ppTMS allows measurement of cortical inhibitory circuit functions. In ppTMS protocols 2 consecutive pulses are delivered to the hand motor region at a fixed interstimulus interval such that the motor-evoked potential, captured by surface EMG sensors, resultant from the second (test) stimulus is modulated by an conditioning stimulus. First resting motor threshold is recorded, which is defined as the lowest stimulus intensity (expressed as a percentage of maximal stimulator output, %MSO) required to induce motor evoked potentials of 50μV. SICI will be elicited with a conditioning stimulus of 70% of resting motor threshold at 2.5ms ISI and 3ms ISI. SICI at each ISI will be reported in %-inhibition and the average calculated for this outcome measure. An increase (positive change from baseline) would indicate a normalisation in this population. Post-dose collected 2-4h post dose on Day1 and Day3 (active vs placebo randomised crossover).
Measured: 2 - 4 hours post dose
Pharmacokinetics: Maximum Plasma Concentrations (Cmax) of AUT00201
Measured: 27 hours
Pharmacokinetics: Area Under the Plasma Concentration-time Curve (AUC) of AUT00201 to the Last Observed Quantifiable Concentration
AUCt
Measured: 27 hours
Change From Baseline in Measures of Dysarthria as Assessed by Speaking Rate Metric From Automated Standardized Speech Test.
Baseline data were collected on Study Day -1 (V2); post-dose data were collected 1 hour post dose on Day 1 (V3) and Day 3 (V5) (active vs placebo randomised crossover).
An increase (positive change from baseline) in syllables/sec would indicate an improvement in this population.
Measured: 1 hour post dose
Change From Baseline in Myoclonus Index (MI; a Measure of Positive Myoclonus) Evaluated With EMG and Accelerometer
Average MI from 0 to 4 hours postdose, calculated during hourly finger-to-nose tasks and Unified Myoclonus Rating Scale Section 4 and 5 tasks, averaged across arms. The Myoclonus Index (MI) is a novel methodology for objectively measuring severity of positive myoclonus. The MI is calculated from positive myoclonus detected using surface electromyography (EMG) and accelerometry data, as described in the publication by Rissanen et al (Clin Neurophysiol. 2021).
People who do not experience myoclonus would be expected to have a score of '0' on the Myoclonus Index; there is no maximum score, although higher scores indicate more severe myoclonus. A reduction of MI (negative change from baseline) would indicate an improvement in this population.
Baseline data are collected on Study Day -1 (V2); post-dose data are collected hourly from dosing to 4 hours post dose, then averaged, on Day 1 (V3) and Day 3 (V5) (active vs placebo randomised crossover).
Measured: 0-4 hours post dose
Change From Baseline in Measures of Dysarthria as Assessed by Buttercup Count From Automated Standardized Speech Test.
Number of times the word "Buttercup" was correctly repeated within 30 seconds. An increase (positive change from baseline) in number of 'buttercups' would indicate an improvement in this population.
Baseline data collected were collected on Study Day -1 (V2); post-dose data were collected 1-hour post-dose on Day 1 (V3) and Day 3 (V5) (active vs placebo randomised crossover).
Measured: 1 hour post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2023
- Study start12 May 2023
- Primary completion1 May 2024
- Study completion1 May 2024
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 Myoclonus Epilepsies, ProgressiveStudies 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
- Crossover
- Model description
- Subjects will be randomized in a 1:1 ratio to one of the two treatments with 3-5 subjects per treatment sequence. Each subject will receive both treatments (100 mg AUT00201 and placebo) with a washout period of 1 day between single doses.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Autifony Therapeutics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Gelfand, MD, Principal investigator, Penn Epilepsy Center, Department of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05873062
- Sponsor's protocol ID
- AUT022201
- Acronym
- AUT022201
- Status last verified
- Mar 2025
- First submitted
- 18 Apr 2023
- Last updated
- 25 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Crossover Study of the Effects of Single Doses of AUT00201 in Patients With Myoclonus Epilepsy and Ataxia Due to Potassium (K+) Channel Mutation (MEAK)
- ClinicalTrials.gov ID
- NCT05873062
- Acronym / sponsor ID
- AUT022201 / AUT022201
- Conditions
- Myoclonus Epilepsies, Progressive
- Keywords
- MEAK, EPM7
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Autifony Therapeutics LimitedIndustry (pharma, biotech, devices)
- Study start
- 12 May 2023 (actual)
- Primary completion
- 1 May 2024 (actual)
- Study completion
- 1 May 2024 (actual)
- First posted
- 24 May 2023 (actual)
- Results
- Posted 25 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, double-blind, placebo-controlled, crossover study to assess the safety, tolerability, and pharmacokinetics of single doses of AUT00201 at 100 mg or matching placebo in patients with myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK).
Detailed description
6 to 10 patients aged 18 years and older, diagnosed with MEAK will be enrolled in the study. Patients will be administered a single dose of AUT00201 and matching placebo in a crossover design. The study is comprised of an outpatient screening and procedure orientation followed by approximately 5 days of an inpatient stay at a clinical research unit. After screening/orientation (Visit 1), and baseline assessments (Visit 2), patients will be administered a single dose of 100 mg of AUT00201 or matching placebo the morning of Visit 3. PK assessments will be done at Visits 3, 4, 5, and 6 from predose and up to 27 hours postdose. Visit 4 will be a washout day for patients. At Visit 5 patients will be administered the crossover treatment. At Visit 6 patients will be discharged from the unit. Safety and tolerability assessments will be conducted throughout. PD parameters will also be assessed. Patients will be followed up by telephone 14 days after discharge.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized in a 1:1 ratio to one of the two treatments with 3-5 subjects per treatment sequence. Each subject will receive both treatments (100 mg AUT00201 and placebo) with a washout period of 1 day between single doses.
| Arm | Type | Receives |
|---|---|---|
| Experimental: AUT00201 | Experimental | Drug: AUT00201Single dose (oral, capsule) of AUT00201 |
| Experimental: Placebo | Placebo comparator | Drug: PlaceboSingle dose matching placebo oral capsules |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female patients aged 18 years or older at time of consenting.
- Diagnosed with MEAK, based on documented genetic evidence of the presence of the KCNC1 (c.959G>A; p.Arg320His) variant.
- If take anticonvulsants, must be on a stable anticonvulsant regiment for at least 30 days prior to Visit 1 and anticipated to remain stable throughout the study or if not on an anticonvulsant regimen, must be stable in regards to seizures for at least 30 days prior to Visit 1 and anticipated to remain stable throughout the study.
- Must be able to participate and willing to give written informed consent. If patient is unable to provide written informed consent, a legally authorized representative can sign on their behalf.
- Must be willing to perform study assessments and comply with the study protocol.
Key exclusion criteria (12 listed)
- Known pathogenic mutation in another gene that causes epilepsy or a different mutation in the KCNC1 gene than the c.959G>A variant.
- Clinically significant metabolic, hepatic, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder.
- Clinically significant abnormal vital signs or laboratory test results.
- Hypersensitivity to AUT00201 or any of the excipients.
- Any medical condition or other factors, as judged by the Investigator, which may interfere with the patient's participation in this study and/or compromise the patient's ability to safely complete the study.
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 |
|---|---|---|
| AUT00201Single oral dose | Drug | Experimental: AUT00201 |
| PlaceboSingle oral dose | Drug | Experimental: Placebo |
Primary outcome
Number of Participants With Treatment-Related Adverse Events After Single Dose Treatment of AUT00201 Compared to Placebo
Time frame: 19 Days
6 secondary outcomes
Change From Baseline in Cortical Inhibition; as Measured by Paired-pulse Transcranial Magnetic Stimulation (ppTMS) at Short Interval Cortical Inhibition (SICI) Inter-stimulus-intervals (ISI): the Outcome is the Average %-Inhibition at SICI 2.5 and 3ms ISI
Time frame: 2 - 4 hours post dose
Pharmacokinetics: Maximum Plasma Concentrations (Cmax) of AUT00201
Time frame: 27 hours
Pharmacokinetics: Area Under the Plasma Concentration-time Curve (AUC) of AUT00201 to the Last Observed Quantifiable Concentration
Time frame: 27 hours
Change From Baseline in Measures of Dysarthria as Assessed by Speaking Rate Metric From Automated Standardized Speech Test.
Time frame: 1 hour post dose
Change From Baseline in Myoclonus Index (MI; a Measure of Positive Myoclonus) Evaluated With EMG and Accelerometer
Time frame: 0-4 hours post dose
Change From Baseline in Measures of Dysarthria as Assessed by Buttercup Count From Automated Standardized Speech Test.
Time frame: 1 hour post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Michael Gelfand, MD principal investigator
Penn Epilepsy Center, Department of Neurology
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 AUT00201 in people with Myoclonus Epilepsies, Progressive, run by Autifony Therapeutics Limited at 1 site in United States.
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 12 inclusion and 12 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 25 Mar 2025. 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 United States. 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 25 Mar 2025). 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 Treatment-Related Adverse Events After Single Dose Treatment of AUT00201 Compared to Placebo (time frame: 19 Days). 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 25 Mar 2025.