ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease (LIFT-AD)

• ClinicalTrials.gov Identifier: NCT04488419
• Recruitment Status: Active, not recruiting
• First Posted: July 28, 2020
• Last Update Posted: January 31, 2024
• Sponsor: Athira Pharma
• Information provided by (Responsible Party): Athira Pharma

Tracking Information

• First Submitted Date: July 23, 2020
• First Posted Date: July 28, 2020
• Last Update Posted Date: January 31, 2024
• Actual Study Start Date: September 28, 2020
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2023)

To evaluate the clinical efficacy of ATH1017 in subjects not on background acetylcholinesterase inhibitors (AChEIs) [ Time Frame: Week 26 ]

The Global Statistical Test (GST) score that combines the change from baseline scores from cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11]) and function (Alzheimer's Disease Cooperative Study-Activities of Daily Living, 23-item version [ADCS-ADL23] score)

Original Primary Outcome Measures (submitted: July 23, 2020)

Overall treatment effect of ATH-1017 as reflected by the Global Statistical Test [ Time Frame: Week 26 ]

The Global Statistical Test (GST) combines the scores from cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11]) and global impression of change (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC]

Current Secondary Outcome Measures (submitted: August 17, 2023)

• Cognition [ Time Frame: Week 26 ]
  Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11] (Range of 0 to 70, where 0 is least impairment and 70 is most severe impairment)
• Activities of Daily Living [ Time Frame: Week 26 ]
  Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-item version [ADCS-ADL23] (Range of 0 to 78, where a higher score indicates greater function)
• To determine the effect of ATH1017 on plasma neurofilament light chain (NfL) concentration [ Time Frame: Week 26 ]
  NfL concentration change from Baseline at Week 26

Original Secondary Outcome Measures (submitted: July 23, 2020)

• Cognition [ Time Frame: Week 26 ]
  Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11]
• Clinical Global Impression of Change [ Time Frame: Week 26 ]
  Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC]
• Activities of Daily Living [ Time Frame: Week 26 ]
  Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-item version [ADCS-ADL23]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease
• Official Title: A Randomized, Placebo-Controlled, Double-Blind Study of ATH-1017 Treatment in Subjects With Mild to Moderate Alzheimer's Disease
• Brief Summary: 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.
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, double-blind, placebo-controlled, parallel-group study

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Alzheimer Disease
• Dementia of Alzheimer Type

Intervention

• Drug: ATH-1017
  Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe
• Drug: Placebo
  Daily subcutaneous (SC) injection of Placebo in a pre-filled syringe

Study Arms

• Experimental: Dosage
  Daily subcutaneous (SC) injection of 40mg ATH-1017
  Intervention: Drug: ATH-1017
• Placebo Comparator: Placebo
  Daily subcutaneous (SC) injection of Placebo
  Intervention: Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 30, 2024): 554
• Original Estimated Enrollment (submitted: July 23, 2020): 300
• Estimated Study Completion Date: August 2024
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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:

  • Treatment-naïve, OR
  • Subjects who received an AChEI in the past and discontinued at least 4 weeks prior to Screening

Key Exclusion Criteria:

• History of significant neurologic disease, other than AD, that may affect cognition, or concurrent with the onset of dementia
• Subject has atypical variant presentation of AD, if known from medical history, particularly non-amnestic AD
• History of brain MRI scan indicative of any other significant abnormality
• Diagnosis of severe major depressive disorder even without psychotic features.
• Significant suicide risk
• History within 2 years of Screening, or current diagnosis of psychosis
• Myocardial infarction or unstable angina within the last 6 months
• Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (note: pacemaker is acceptable)
• Subject has either hypertension or symptomatic hypotension
• Clinically significant ECG abnormality at Screening
• Chronic kidney disease with estimated glomerular filtration rate (eGFR) <45 mL/min
• Hepatic impairment with alanine aminotransferase or aspartate aminotransferase > 2 times the upper limit of normal, or Child-Pugh class B and C
• Malignant tumor within 3 years before Screening
• Memantine in any form, combination or dosage within 4 weeks prior to Screening
• Acetylcholinesterase inhibitors in any dosage form
• The subject has received active amyloid or tau immunization (i.e., vaccination for Alzheimer's disease) at any time, or passive immunization (i.e., monoclonal antibodies for Alzheimer's disease) within 6 months of Screening

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04488419
• Other Study ID Numbers: ATH-1017-AD-0201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Athira Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Athira Pharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Athira Pharma
• Verification Date: January 2024