A Study of LY3303560 in Participants With Mild Cognitive Impairment or Alzheimer's Disease

NCT03019536 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 16452I8G-MC-LMDD2016-002102-39
• Study Type: interventional
• Target: 22
• Locations: 3 countries
• Sites: 11

Brief Summary

The study involves repeated doses of LY3303560 given by infusion for 49 weeks. The study will examine how safe repeated doses of LY3303560 are, whether they cause side effects in participants with mild cognitive impairment or Alzheimer's Disease, and how LY3303560 is handled by the body and acts in the body. This study will last up to 65 weeks, not including screening. Screening is required within 90 days prior to the start of the study.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

  A summary of other non-serious adverse events (AEs), and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

  Baseline up to Week 65

Secondary Outcomes (2)

• Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3303560 at Week 49

  Week 49 (Pre-dose, 0.5, 2, 4, 8, 336, 672, 1344, 2016, 2688 hours post-dose)

• Pharmacokinetics: Area Under the Serum Concentration Time Curve During the Dosing Interval (AUC 0-tau) of LY3303560

  Week 49 (Pre-dose, 0.5, 2, 4, 8, 336, 672, 1344, 2016, 2688 hours post-dose)

Study Arms (3)

70 mg LY3303560

EXPERIMENTAL

70 milligram (mg) LY3303560 administered intravenously (IV) every 4 weeks for 25 weeks with the option of continuing treatment up to 49 weeks (up to 6 further doses), followed by a 16-week follow-up period.

Drug: LY3303560 - IV; Drug: Placebo - IV; Drug: Florbetapir F 18; Drug: Flortaucipir F18

210 mg LY3303560

EXPERIMENTAL

210 mg LY3303560 administered IV every 4 weeks for 25 weeks with the option of continuing treatment up to 49 weeks (up to 6 further doses), followed by a 16-week follow-up period.

Drug: LY3303560 - IV; Drug: Placebo - IV; Drug: Florbetapir F 18; Drug: Flortaucipir F18

Placebo IV

EXPERIMENTAL

Placebo administered intravenously (IV) every 4 weeks for 25 weeks with the option of continuing treatment up to 49 weeks (up to 6 further doses),, followed by a 16-week follow-up period.

Drug: Placebo - IV; Drug: Florbetapir F 18; Drug: Flortaucipir F18

Interventions

LY3303560 - IV DRUG

Administered IV

210 mg LY3303560; 70 mg LY3303560

Placebo - IV DRUG

Administered IV

210 mg LY3303560; 70 mg LY3303560; Placebo IV

Florbetapir F 18 DRUG

Administered IV during the Positron Emission Tomography (PET) scan performed during screening.

210 mg LY3303560; 70 mg LY3303560; Placebo IV

Flortaucipir F18 DRUG

Administered IV during the PET scan performed during the study.

Also known as: AV-1451, [F-18]T807, LY3191748

210 mg LY3303560; 70 mg LY3303560; Placebo IV

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild-to-moderate AD based on National Institute of Aging and Alzheimer's Association diagnostic criteria
• Female participants: women not of child-bearing potential may participate, and include those who are:
• Infertile due to surgical sterilisation (hysterectomy, bilateral oophorectomy, or for countries outside of Japan, tubal ligation), congenital anomaly such as mullerian agenesis; or
• Postmenopausal defined as women at least 50 years of age with an intact uterus who have not taken hormones or oral contraceptives within 1 year, who have had either cessation of menses for at least 1 year, or 6 to 12 months of spontaneous amenorrhea with follicle-stimulating greater than (\>) 40 milli-international units per millilitre (mIU/mL)
• Have a body weight of at least 50 kilogram (kg) (except for Japanese sites) and have a body mass index (BMI) of 18.0 to 35.0 kilogram per meter square (kg/m²) (for all sites), inclusive, at screening

You may not qualify if:

• Are currently enrolled in a clinical trial involving an investigational product (IP) or any other type of medical research judged not to be scientifically or medically compatible with this study
• Have participated, within the last 30 days (3 months and 4 months for sites in the European Union \[EU\] and Japan, respectively) in a clinical trial involving an IP. If the previous IP has a long half-life, 3 months (4 months for sites in Japan) or 5 half-lives (whichever is longer) should have passed
• Have known allergies to LY3303560, related compounds or any components of the formulation, or history of significant atopy
• Have significant allergies to humanised monoclonal antibodies, diphenhydramine, adrenaline, or methylprednisolone; or have a history of clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids, or severe post treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis)
• Have an increased risk of seizures as evidenced by a history of head trauma with loss of consciousness within the last 5 years or any seizure; prior electroencephalogram with epileptiform activity; surgery to the cerebral cortex; or history within the last 5 years of a serious infectious disease affecting the brain
• Have any contraindications for Magnetic Resonance Imaging (MRI) studies, including claustrophobia, or the presence of metal (ferromagnetic) implants or a cardiac pacemaker
• Have a history of intracranial haemorrhage, cerebrovascular aneurysm, or arteriovenous malformation, carotid artery occlusion, or epilepsy
• Have received acetylcholinesterase inhibitors (AChEIs), memantine, and/or other AD therapy for less than 4 weeks, or have less than 4 weeks of stable therapy on these treatments by time of randomisation (including less than 4 weeks since stopping AChEIs and/or memantine); or have received medications that affect the central nervous system, except treatments for AD, for less than 4 weeks at a stable dose
• Are currently using or intend to use drugs known to significantly prolong the QT interval, or who have a known risk factor for Torsades de Pointes. A participant will not be excluded if they have been using stable medication that is known to potentially cause significant prolongation of the QT interval, but does not present with any clinically significant prolongation of the QT interval at screening, in the opinion of the investigator
• History of cancer within the last 5 years, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-progressive prostate cancer, or other cancers with low risk of recurrence or spread.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (11)

Bioclinica

Melbourne, Florida, 32940, United States

Location

Bioclinica

Orlando, Florida, 32806, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Bioclinica

The Villages, Florida, 32162, United States

Location

Princeton Medical Institute

Princeton, New Jersey, 08540, United States

Location

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

Bunkyō City, 113-8655, Japan

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Hyōgo, 650-0047, Japan

Location

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

Kurume, 830-0011, Japan

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Tokyo, 192-0071, Japan

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.

Bath, BA1 3NG, United Kingdom

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

London, W6 8RF, United Kingdom

Location

Related Publications (1)

• Willis BA, Lo AC, Dage JL, Shcherbinin S, Chinchen L, Andersen SW, LaBell ES, Perahia DGS, Hauck PM, Lowe SL. Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial. J Alzheimers Dis Rep. 2023 Sep 15;7(1):1015-1024. doi: 10.3233/ADR-230012. eCollection 2023.

  PMID: 37849628 DERIVED

Related Links

• Click here for more information about this study: A Study of LY3303560 in Participants With Mild Cognitive Impairment or Alzheimer's Disease

MeSH Terms

Conditions

Alzheimer Disease

Interventions

florbetapir; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 12, 2017
• Study Start: January 31, 2017
• Primary Completion: June 5, 2019
• Study Completion: June 5, 2019
• Last Updated: October 10, 2023
• Results First Posted: October 10, 2023

Record last verified: 2023-10-01

Locations

JP (4); GB (2); US (5)