Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study is designed to evaluate safety and efficacy of fosgonimeton (ATH-1017) in the treatment of mild to moderate Alzheimer's disease with a randomized treatment duration of 26-weeks.
The study is designed to evaluate safety and efficacy of ATH-1017 in mild to moderate AD subjects, with randomized, parallel-arm treatment duration of 26 weeks, and based on clinical diagnostic criteria of Alzheimer's disease. Clinical efficacy is demonstrated by improvement in cognition and global/functional assessments comparing treatment to placebo.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dosage | Experimental | Daily subcutaneous (SC) injection of 40mg ATH-1017 |
|
| Placebo | Placebo Comparator | Daily subcutaneous (SC) injection of Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATH-1017 | Drug | Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Global Statistical Test (GST) Score | The Global Statistical Test (GST) score is a composite of cognition and function, calculated as the average of two change from baseline z-scores; the z-scores are calculated for the change from baseline scores for cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11]; lower value indicates improvement) and function (Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-item version [ADCS-ADL23] score; higher value indicates improvement). GST is a standardized score relative to the population mean. Therefore, a GST score of 0 is representative of the population mean. Since GST is a composite of two endpoints, a negative ADCS-ADL23 score is used in deriving GST. Therefore, a lower score indicates improvement, and a higher score indicates worsening. There are no defined clinically relevant thresholds for this GST score. | Baseline and Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) Change From Baseline | The ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. The standard 11 items (and corresponding score range) were: word recall (0-10), commands (0-5), constructional praxis (0-5), naming objects and fingers (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), spoken language ability (0-5), comprehension of spoken language (0-5), word-finding difficulty (0-5), and remembering test instructions (0-5). The test included 7 performance items and 4 clinician-rated items. The ADAS-Cog11 total score was the sum of all 11 individual items, with a total score ranging from 0 (no impairment) to 70 (severe impairment). Higher scores indicated more severe cognitive impairment. Baseline was defined as Day 1. |
Not provided
Key Inclusion Criteria:
Age 55 to 85 years
Mild-to-moderate AD dementia subjects, MMSE 14-24, CDR 1 or 2 at Screening
Clinical diagnosis of dementia, due probably to AD, by Revised National Institute on Aging-Alzheimer's Association criteria (McKhann, 2011)
Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m2 at Screening
Reliable and capable support person/caregiver
Treatment-free (subjects not receiving acetylcholinesterase inhibitor [AChEI] treatment), defined as:
Key Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Javier San Martin, MD | Chief Medical Officer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Rochester-AD-CARE Program | Rochester | New York | 14620 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21514250 | Background | McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21. | |
| 38599894 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the clinical efficacy of ATH-1017 treatment compared with placebo in participants with a clinical diagnosis of mild to moderate Alzheimer's disease (AD).
The study was conducted in the United States.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | ATH-1017 40 Milligrams (mg) | Participants were randomized to receive ATH-1017 40 mg via 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 |
| FG002 | ATH-1017 70 mg | Participants were randomized to receive ATH-1017 70 mg via 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Safety Population, >=1 Dose Administered |
|
| |||||||||||||||||||||
| Primary Analysis Population |
|
Safety Population: included all randomized participants who received at least one dose of the study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Global Statistical Test (GST) Score | The Global Statistical Test (GST) score is a composite of cognition and function, calculated as the average of two change from baseline z-scores; the z-scores are calculated for the change from baseline scores for cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11]; lower value indicates improvement) and function (Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-item version [ADCS-ADL23] score; higher value indicates improvement). GST is a standardized score relative to the population mean. Therefore, a GST score of 0 is representative of the population mean. Since GST is a composite of two endpoints, a negative ADCS-ADL23 score is used in deriving GST. Therefore, a lower score indicates improvement, and a higher score indicates worsening. There are no defined clinically relevant thresholds for this GST score. | Primary Analysis Population (Placebo or 40 mg ATH-1017 mITT Participants not taking AChEIs) | Posted | Least Squares Mean | Standard Error | Z-score | Baseline and Week 26 |
|
Up to 30 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block second degree | Cardiac disorders | MedDRA (24.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site reactions | General disorders | MedDRA (24.0) | Systematic Assessment | (high-level term) |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Javier San Martin, CMO | Athira Pharma | 1-866-725-0930 | clinicaltrials@athira.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 21, 2024 | Mar 10, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 13, 2024 | Mar 10, 2025 | SAP_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
Not provided
Not provided
Randomized, double-blind, placebo-controlled, parallel-group study
Not provided
Not provided
Not provided
| Placebo |
| Drug |
Daily subcutaneous (SC) injection of Placebo in a pre-filled syringe |
|
| Baseline and Week 26 |
| Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-Item Version (ADCS-ADL23) Change From Baseline | The ADCS-ADL23 is a 23-item assessment of functional impairment in terms of activities of daily living administered to the support person/caregiver. It comprises 23 questions about the subject's involvement and level of performance across items representing daily living. The questions range from basic to instrumental activities of daily living. Each item is rated from the highest level of independent performance to complete loss. The total score range is from 0 to 78, with lower scores indicating greater functional impairment. Baseline was defined as Day 1. | Baseline and Week 26 |
| Plasma Neurofilament Light Chain (NfL) Concentrations Change From Baseline | Neurofilament light chain (NfL) is an objective biomarker of neurodegeneration and was measured to quantitatively support the evaluation of ATH-1017. Higher concentrations of NfL in plasma are associated with neurodegeneration. | Baseline and Week 26 |
| Derived |
| Reda SM, Setti SE, Berthiaume AA, Wu W, Taylor RW, Johnston JL, Stein LR, Moebius HJ, Church KJ. Fosgonimeton attenuates amyloid-beta toxicity in preclinical models of Alzheimer's disease. Neurotherapeutics. 2024 Jul;21(4):e00350. doi: 10.1016/j.neurot.2024.e00350. Epub 2024 Apr 9. |
| Lost to Follow-up |
|
| Protocol Violation |
|
| Lack of Efficacy |
|
| Physician Decision |
|
| Undetermined |
|
| >1 Reason |
|
| NOT COMPLETED |
|
|
| BG001 | ATH-1017 40 Milligrams (mg) | Participants were randomized to receive ATH-1017 40 mg via 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 |
| BG002 | ATH-1017 70 mg | Participants were randomized to receive ATH-1017 70 mg via 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 | Placebo | Daily subcutaneous (SC) injection of Placebo Placebo: Daily subcutaneous (SC) injection of Placebo in a pre-filled syringe |
| OG001 | ATH-1017 40 Milligrams (mg) | Daily subcutaneous (SC) injection of 40mg ATH-1017 ATH-1017: Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe |
|
|
| Secondary | Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) Change From Baseline | The ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. The standard 11 items (and corresponding score range) were: word recall (0-10), commands (0-5), constructional praxis (0-5), naming objects and fingers (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), spoken language ability (0-5), comprehension of spoken language (0-5), word-finding difficulty (0-5), and remembering test instructions (0-5). The test included 7 performance items and 4 clinician-rated items. The ADAS-Cog11 total score was the sum of all 11 individual items, with a total score ranging from 0 (no impairment) to 70 (severe impairment). Higher scores indicated more severe cognitive impairment. Baseline was defined as Day 1. | Primary Analysis Population (Placebo or 40 mg ATH-1017 mITT Participants not taking AChEIs) | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Week 26 |
|
|
|
| Secondary | Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-Item Version (ADCS-ADL23) Change From Baseline | The ADCS-ADL23 is a 23-item assessment of functional impairment in terms of activities of daily living administered to the support person/caregiver. It comprises 23 questions about the subject's involvement and level of performance across items representing daily living. The questions range from basic to instrumental activities of daily living. Each item is rated from the highest level of independent performance to complete loss. The total score range is from 0 to 78, with lower scores indicating greater functional impairment. Baseline was defined as Day 1. | Primary Analysis Population (Placebo or 40 mg ATH-1017 mITT Participants not taking AChEIs) | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and Week 26 |
|
|
|
| Secondary | Plasma Neurofilament Light Chain (NfL) Concentrations Change From Baseline | Neurofilament light chain (NfL) is an objective biomarker of neurodegeneration and was measured to quantitatively support the evaluation of ATH-1017. Higher concentrations of NfL in plasma are associated with neurodegeneration. | Primary Analysis Population (Placebo or 40 mg ATH-1017 mITT Participants not taking AChEIs) | Posted | Least Squares Mean | Standard Error | picogram / milliter | Baseline and Week 26 |
|
|
|
| 0 |
| 218 |
| 15 |
| 218 |
| 65 |
| 218 |
| EG001 | ATH-1017 40 Milligrams (mg) | Participants were randomized to receive ATH-1017 40 mg via 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 | 0 | 224 | 11 | 224 | 185 | 224 |
| EG002 | ATH-1017 70 mg | Participants were randomized to receive ATH-1017 70 mg via 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 | 0 | 107 | 3 | 107 | 104 | 107 |
| Diarrhoea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Diverticulum intestinal haemorrhagic | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Faecaloma | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Colitis ischaemic | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA (24.0) | Systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA (24.0) | Systematic Assessment |
|
| COVID-19 pneumonia | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Pneumonia viral | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Traumatic arthropathy | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.0) | Systematic Assessment |
|
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
|
| COVID-19 | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
|
Not provided
| D019636 |
| Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |