Trial Outcomes & Findings for Safety, Blood Levels and Effects of AUT00201 in Patients With MEAK (NCT NCT05873062)

NCT ID: NCT05873062

Last Updated: 2025-03-25

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: 19 Days
• Results posted on: 2025-03-25

Participant Flow

Five unique patients were enrolled, however one patient was enrolled (signing two informed consent forms) and completed the study twice, in line with Protocol Amendment #3, resulting 6 participants being enrolled and completing the study. Six participants are reported for safety and PK data, the 5 unique are reported for baseline and demographics, and the numbers reported are indicated for each PD outcome.

All 6 participants who signed the informed consent form completed the study.

Participant milestones

Measure	Experimental: AUT00201 / Placebo Single dose of AUT00201 (oral, capsule) followed by a single dose of placebo to match	Experimental: Placebo / AUT00201 Single dose of matching placebo (oral, capsule) followed by a single dose of AUT00201 (oral, capsule)
Overall Study STARTED	3	3
Overall Study COMPLETED	3	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Blood Levels and Effects of AUT00201 in Patients With MEAK

Baseline characteristics by cohort

Measure	Experimental: AUT00201 / Placebo n=2 Participants Single dose of AUT00201 (oral, capsule) followed by a single dose of placebo to match	Experimental: Placebo / AUT00201 n=3 Participants Single dose matching placebo (oral, capsule) followed by a single dose of AUT00201 (oral, capsule)	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: 19 Days

Population: Safety Population

Outcome measures

Measure	Experimental: AUT00201 n=6 Participants Single dose of AUT00201 (oral, capsule)	Experimental: Placebo n=6 Participants Single dose of matching placebo (oral, capsule)
Number of Participants With Treatment-Related Adverse Events After Single Dose Treatment of AUT00201 Compared to Placebo	5 Participants	5 Participants

SECONDARY outcome

Timeframe: 2 - 4 hours post dose

Population: Modified Pharmacodynamic Population. Values reported are changes from baseline in the average SICI 2.5 and 3ms measurements from the 2 to 4 hour postdose assessment.

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).

Outcome measures

Measure	Experimental: AUT00201 n=3 Participants Single dose of AUT00201 (oral, capsule)	Experimental: Placebo n=3 Participants Single dose of matching placebo (oral, capsule)
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	4.0300 % inhibition Standard Deviation 5.8674	4.0050 % inhibition Standard Deviation 8.6771

SECONDARY outcome

Timeframe: 27 hours

Population: No subjects analysed for PK parameters following the placebo dose

Outcome measures

Measure	Experimental: AUT00201 n=6 Participants Single dose of AUT00201 (oral, capsule)	Experimental: Placebo Single dose of matching placebo (oral, capsule)
Pharmacokinetics: Maximum Plasma Concentrations (Cmax) of AUT00201	411 ng/mL Standard Deviation 273	—

SECONDARY outcome

Timeframe: 27 hours

Population: No PK parameters were analysed following placebo dose

AUCt

Outcome measures

Measure	Experimental: AUT00201 n=6 Participants Single dose of AUT00201 (oral, capsule)	Experimental: Placebo Single dose of matching placebo (oral, capsule)
Pharmacokinetics: Area Under the Plasma Concentration-time Curve (AUC) of AUT00201 to the Last Observed Quantifiable Concentration	2110 ng*h/mL Standard Deviation 1170	—

SECONDARY outcome

Timeframe: 1 hour post dose

Population: Modified Pharmacodynamic Population

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.

Outcome measures

Measure	Experimental: AUT00201 n=4 Participants Single dose of AUT00201 (oral, capsule)	Experimental: Placebo n=5 Participants Single dose of matching placebo (oral, capsule)
Change From Baseline in Measures of Dysarthria as Assessed by Speaking Rate Metric From Automated Standardized Speech Test.	0.7014 syllables/sec Standard Deviation 0.6318	0.2161 syllables/sec Standard Deviation 0.4487

SECONDARY outcome

Timeframe: 0-4 hours post dose

Population: Modified Pharmacodynamic Population

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).

Outcome measures

Measure	Experimental: AUT00201 n=5 Participants Single dose of AUT00201 (oral, capsule)	Experimental: Placebo n=5 Participants Single dose of matching placebo (oral, capsule)
Change From Baseline in Myoclonus Index (MI; a Measure of Positive Myoclonus) Evaluated With EMG and Accelerometer	0.4556 Index Standard Deviation 1.1175	0.4257 Index Standard Deviation 1.0254

SECONDARY outcome

Timeframe: 1 hour post-dose

Population: Modified Pharmacodynamic Population

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).

Outcome measures

Measure	Experimental: AUT00201 n=3 Participants Single dose of AUT00201 (oral, capsule)	Experimental: Placebo n=4 Participants Single dose of matching placebo (oral, capsule)
Change From Baseline in Measures of Dysarthria as Assessed by Buttercup Count From Automated Standardized Speech Test.	0.0 Number correct "Buttercup"s in 30seconds Standard Deviation 1.0	-0.3 Number correct "Buttercup"s in 30seconds Standard Deviation 1.0

Adverse Events

Experimental: AUT00201

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Experimental: Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Experimental: AUT00201 n=6 participants at risk Single dose of AUT00201 (oral, capsule)	Experimental: Placebo n=6 participants at risk Single dose of matching placebo (oral, capsule)
Gastrointestinal disorders Upper Abdominal Pain	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	33.3% 2/6 • Number of events 2 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	16.7% 1/6 • Number of events 1 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
General disorders Application Site Haemorrhage	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	16.7% 1/6 • Number of events 1 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
General disorders Catheter Site Pain	50.0% 3/6 • Number of events 3 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	33.3% 2/6 • Number of events 2 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
Injury, poisoning and procedural complications Contusion	16.7% 1/6 • Number of events 1 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
Metabolism and nutrition disorders Decreased Appetite	16.7% 1/6 • Number of events 1 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
Musculoskeletal and connective tissue disorders Neck Pain	16.7% 1/6 • Number of events 1 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
Nervous system disorders Generalised Tonic-Clonic Seizure	16.7% 1/6 • Number of events 1 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
Nervous system disorders Headache	33.3% 2/6 • Number of events 2 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	33.3% 2/6 • Number of events 2 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
Nervous system disorders Myoclonic Epilepsy	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	16.7% 1/6 • Number of events 1 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).
Nervous system disorders Tremor	16.7% 1/6 • Number of events 1 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).	0.00% 0/6 • Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).

Additional Information

Head of Clinical Project Management

Autifony Therapeutics Ltd

Phone: +447909228562

Email: Alice.Sharman@autifony.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place