Trial Outcomes & Findings for ATH-1017 Treatment in Subjects With Parkinson's Disease Dementia or Dementia With Lewy Bodies (SHAPE Trial) (NCT NCT04831281)

Last Updated: 2025-03-04

Results Overview

The Global Statistical Test (GST) score is a composite of the change from baseline (CFB) z-scores to Week 26 in the Alzheimer's Disease Assessment Scale - Cognitive Subscale, 13-Item Version (ADAS-Cog13; range 0-85; higher scores indicate greater impairment) and Event Related Potential P300 Latency (ERP P300; longer latency (milliseconds) indicates greater impairment). This composite approach was used to assess overall change in disease status and treatment effects of ATH-1017. The GST score was defined as a single outcome variable based on standardizing and combining individual patient-level z-score of change from baseline cognition (ADAS-Cog13) and ERP P300 latency scores. The between-group difference was calculated by subtracting the mean GST score for placebo from the mean GST score for ATH-1017. A negative value based on GST scores (ATH-1017 minus placebo) indicates a favorable response to ATH-1017, while a positive value favors placebo.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Baseline

Results posted on

2025-03-04

Participant Flow

The study was conducted at a total of 7 centers in the United States (US).

This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study comparing ATH-1017 40 milligrams per day (mg/day) and ATH-1017 70 mg/day with placebo in participants with Parkinson's Disease Dementia or Dementia with Lewy Bodies.

Participant milestones

Participant milestones
Measure	Placebo Participants were randomized to receive placebo via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 40 Milligrams (mg) Participants were randomized to receive ATH-1017 40mg via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 70 mg Participants were randomized to receive ATH-1017 70mg via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30
Overall Study STARTED	9	9	10
Overall Study COMPLETED	7	7	5
Overall Study NOT COMPLETED	2	2	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were randomized to receive placebo via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 40 Milligrams (mg) Participants were randomized to receive ATH-1017 40mg via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 70 mg Participants were randomized to receive ATH-1017 70mg via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30
Overall Study Adverse Event	1	0	3
Overall Study Withdrawal by Subject	0	1	2
Overall Study Undetermined	1	1	0

Baseline Characteristics

ATH-1017 Treatment in Subjects With Parkinson's Disease Dementia or Dementia With Lewy Bodies (SHAPE Trial)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=9 Participants Participants were randomized to receive placebo via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 40 mg n=9 Participants Participants were randomized to receive ATH-1017 40 mg via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 70 mg n=10 Participants Participants were randomized to receive ATH-1017 70 mg via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	Total n=28 Participants Total of all reporting groups
Age, Continuous	74.9 years STANDARD_DEVIATION 4.86 • n=5 Participants	70.7 years STANDARD_DEVIATION 9.89 • n=7 Participants	74.2 years STANDARD_DEVIATION 7.5 • n=5 Participants	73.3 years STANDARD_DEVIATION 7.62 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	27 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	27 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline

Population: Modified intent to treat population.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants were randomized to receive placebo via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 40 mg n=7 Participants Participants were randomized to receive ATH-1017 40 mg via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 70 mg n=9 Participants Participants were randomized to receive ATH-1017 70 mg via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30
Global Statistical Test (GST) Score at Baseline	-0.222 Z-score Standard Deviation 0.6365	0.332 Z-score Standard Deviation 0.6337	-0.036 Z-score Standard Deviation 1.0050

SECONDARY outcome

Timeframe: Baseline

Population: Modified intent to treat population.

ERP P300 was a method of recording brain activity elicited by external stimuli, for example (e.g.), an oddball auditory stimulus, particularly of working memory access. The participant had to perform a task related to auditory stimuli in order to assess the P300 component (latency). The stimulus consisted of an oddball paradigm with 2 sound stimuli. Stimuli were presented through headphones and auditory stimulation for P300 was assessed in a recording lasting up to 10 minutes. It was calculated as the average across the pre-dose values at Baseline visit.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants were randomized to receive placebo via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 40 mg n=7 Participants Participants were randomized to receive ATH-1017 40 mg via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 70 mg n=9 Participants Participants were randomized to receive ATH-1017 70 mg via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30
Event-related Potential (ERP) P300 Latency at Baseline	381.84 Millisecond (ms) Standard Deviation 51.739	373.19 Millisecond (ms) Standard Deviation 18.669	367.84 Millisecond (ms) Standard Deviation 45.635

SECONDARY outcome

Timeframe: Baseline

Population: Modified intent to treat population.

The Alzheimer's Disease Assessment Scale - Cognitive Subscale, 13-Item Version (ADAS-Cog13) is designed to measure cognitive symptom change. The test comprises 9 performance items and 4 clinician-rated items (total score ranging from 0 to 85). Higher scores indicate more severe cognitive impairment.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants were randomized to receive placebo via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 40 mg n=7 Participants Participants were randomized to receive ATH-1017 40 mg via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 70 mg n=9 Participants Participants were randomized to receive ATH-1017 70 mg via subcutaneous (SC) injection QD preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) at Baseline	16.9 score on a scale Standard Deviation 6.94	29.7 score on a scale Standard Deviation 10.03	23.8 score on a scale Standard Deviation 11.49

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

ATH-1017 40 Milligrams (mg)

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

ATH-1017 70 mg

Serious events: 1 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=9 participants at risk Participants were randomized to receive placebo via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 40 Milligrams (mg) n=9 participants at risk Participants were randomized to receive ATH-1017 40mg via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30	ATH-1017 70 mg n=10 participants at risk Participants were randomized to receive ATH-1017 70mg via subcutaneous (SC) injection once-daily (QD) preferably during daytime. The first SC injection of study drug was performed at site under supervision. The participant should withhold study drug administration on the day of subsequent clinic visits; study drug administration was done on site under supervision of site staff at these visits. Clinic visits took place on Day 1 and thereafter at Weeks 2, 6, 12, 16, 20, and 26, with a safety follow-up visit scheduled 4 weeks after completion of the double-blind period at Week 30
Injury, poisoning and procedural complications Femoral neck fracture	11.1% 1/9 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.	0.00% 0/9 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.	0.00% 0/10 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/9 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.	0.00% 0/9 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.	10.0% 1/10 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.
Psychiatric disorders Psychotic symptom	0.00% 0/9 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.	11.1% 1/9 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.	0.00% 0/10 • Up to Week 30 Safety population which included all randomized participants who received at least one dose of the study medication.

Other adverse events

Additional Information

Dr. Javier San Martin, CMO

Athira Pharma

Phone: 1-866-725-0930

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place