A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY4066708 in Healthy Participants

NCT07046559 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 27332J5Z-MC-OTAA
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to explore the safety and any side effects of LY4066708 in healthy participants. The study will also measure how much LY4066708 gets into the bloodstream and the central nervous system and how long it takes the body to remove it. The study will last up to 24 weeks for each participant.

Conditions

Healthy; Cancer

Outcome Measures

Primary Outcomes (2)

• Part A: Number of Participants with One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration

  A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Adverse Events module

  Baseline up to Week 12

• Part B: Number of Participants with One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration

  A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Adverse Events module

  Screening to Day 22

Secondary Outcomes (4)

• Part A: Pharmacokinetics (PK)- Area Under the Plasma Concentration Versus Time Curve (AUC0-168)

  Predose up to day 15

• Part B: Pharmacokinetics (PK)- AUC0-168

  Day 1 up to day 7

• Part A: Pharmacokinetics (PK)- Maximum Observed Drug Concentration (Cmax)

  Predose up to day 15

• Part B: Pharmacokinetics (PK)- Cmax

  After dose 3, up to day 64

Study Arms (15)

Part A Cohort 1: Single-Ascending Dose (SAD)- LY4066708

EXPERIMENTAL

LY4066708 administered by intravenous (IV) injection

Drug: LY4066708

Part A Cohort 2: SAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part A Cohort 3A: SAD- LY4066708

EXPERIMENTAL

LY4066708 administered by subcutaneous (SC) injection

Drug: LY4066708

Part A Cohort 3B: SAD- LY4066708

EXPERIMENTAL

LY4066708 administered by SC injection

Drug: LY4066708

Part A Cohort 4: SAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part A Cohort 5: SAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part A Cohort 5A: SAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part A Cohort 6A: SAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part A Cohort 6: SAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part B Cohort 1: Multiple-Ascending Dose (MAD)- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part B Cohort 2: MAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part B Cohort 3: MAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Part B Cohort 4: MAD- LY4066708

EXPERIMENTAL

LY4066708 administered by IV injection

Drug: LY4066708

Placebo

PLACEBO COMPARATOR

Placebo administered by IV injection

Drug: Placebo

Placebo- Part A Cohort 3A and Part A Cohort 3B.

PLACEBO COMPARATOR

Placebo administered by SC injection

Drug: Placebo

Interventions

LY4066708 DRUG

Administered IV

Part A Cohort 1: Single-Ascending Dose (SAD)- LY4066708; Part A Cohort 2: SAD- LY4066708; Part A Cohort 4: SAD- LY4066708; Part A Cohort 5: SAD- LY4066708; Part A Cohort 5A: SAD- LY4066708; Part A Cohort 6: SAD- LY4066708; Part A Cohort 6A: SAD- LY4066708; Part B Cohort 1: Multiple-Ascending Dose (MAD)- LY4066708; Part B Cohort 2: MAD- LY4066708; Part B Cohort 3: MAD- LY4066708; Part B Cohort 4: MAD- LY4066708

Placebo DRUG

Administered IV

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Japanese Participants Only: To qualify as a participant of first-generation Japanese origin, the participant, the participant's biological parents, and all the participant's biological grandparents must be of exclusive Japanese descent and born in Japan.
• Chinese Participants Only: To qualify as Chinese for the purpose of this study, all 4 of the participants' biological grandparents must be of exclusive Chinese descent and born in China, Hong Kong, Macau, or Taiwan.
• Have a body mass index (BMI) at the time of screening within the range 18.5 to 30 kilogram per meter squared (kg/m²) (inclusive).
• Participants assigned female at birth (AFAB) not of childbearing potential and participants assigned male at birth (AMAB) willing to practice effective contraception throughout the study may participate.
• Willingness to undergo study procedures which may include repeated lumbar punctures

You may not qualify if:

• Are individuals of childbearing potential (IOCBP). Notwithstanding their IOCBP status, participants AFAB are excluded if they are breastfeeding.
• A history of additional risk factors for Torsades de Pointes (for example, heart failure, hypokalemia, family history of Long QT Syndrome).
• The use of concomitant medications that prolong the QT/QTc interval.
• Have known allergies to LY4066708 or any components of the formulation, or history of allergic reactions to any transferrin receptor (TfR) antibodies.
• Have participated, within the 3 months of screening, in a clinical trial involving a study intervention (other than the study intervention used in this study). If the previous investigational product has a long half-life (t½), 3 months or 5 half-lives (whichever is longer) should have passed.
• Have a 12-lead electrocardiogram (ECG) abnormality at screening that, in the opinion of the investigator, increases the risks associated with participating in the study, or may confound ECG data analysis.
• Show evidence of hepatitis C and/or positive hepatitis C antibody.
• Current infection with hepatitis B virus (HBV) or evidence of past infection with HBV, that is, positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core total antibody (anti-HBc).
• A marked baseline prolongation of time from the start of the Q wave to the end of the T wave/ corrected QT interval (QT/QTc) interval (for example, repeated demonstration of a corrected time from the start of the Q wave to the end of the T wave interval - Fridericia formula (QTcF) interval greater than 450 ms).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Fortrea Clinical Research Unit

Holbeck, Leeds, LS11 9EH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasms

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

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: May 13, 2025
• First Posted: July 1, 2025
• Study Start: May 13, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)