NCT07155980

Brief Summary

This is a randomized, double-blinded, placebo-controlled dose escalating first in human study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) of GSM-779690T. The study will have two parts: a single ascending dose (SAD) component and a multiple ascending dose (MAD) component. The goal of this study is to learn if GSM-779690T is safe and to assess the effects on levels of specific Aβ peptide isoforms in adults. SAD: A total of 48 healthy volunteers are planned to be consented and enrolled to receive a single oral dose of GSM-779690T at increasing strengths or placebo in Cohorts 1 through 6. MAD: A total of 48 healthy volunteers are planned to be consented and enrolled to receive multiple oral doses of GSM-779690T (doses will be informed by SAD data) in Cohorts 7 through 10. Cohort 10 will include healthy older-adults. Participants who have signed an informed consent and meet screening eligibility requirements will be randomly assigned to receive a single oral dose of GSM-779690T or placebo with a 3:1 (active: placebo) ratio at each dose level. The decision to escalate between dose levels in the SAD and to proceed to the MAD will be based on Data Review Committee review of prior cohorts, safety, tolerability, and PK data. The study treatment, GSM-779690T, and all protocol assessments will be administered at the study site by trained study site personnel.

Trial Health

50
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Timeline
1mo left

Started Nov 2025

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress89%
Nov 2025Jul 2026

First Submitted

Initial submission to the registry

August 13, 2025

Completed
22 days until next milestone

First Posted

Study publicly available on registry

September 4, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

November 9, 2025

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 11, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 11, 2026

Last Updated

January 7, 2026

Status Verified

January 1, 2026

Enrollment Period

8 months

First QC Date

August 13, 2025

Last Update Submit

January 5, 2026

Conditions

Healthy Adult Participants

Keywords

gamma-secretase modulatorAlzheimer's diseasePharmacokineticspharmacodynamicsbeta-amyloidsingle ascending dosemultiple ascending dose

Outcome Measures

Primary Outcomes (1)

  • Number and percentage of participants reporting treatment-emergent adverse events and serious adverse events after single and multiple oral doses of GSM-779690-T

    Treatment emergent adverse events and serious adverse events will be summarized for each treatment group. The frequencies of treatment emergent adverse events and serious adverse events between the participants in each group will be compared.

    From enrollment through study completion, approximately 7 days in groups 1, 2, 3, and 6; 14 days in groups 4 and 5; and 21 days in groups 7, 8, 9, and 10.

Other Outcomes (3)

  • Pharmacokinetic parameter of area under the curve (AUC) calculation after single and multiple oral doses of GSM-779690-T

    SAD Groups 1, 2, 3, 6 Days 0 to 7 post-dose (plasma); SAD Groups 4 and 5 Days 0 to 10 post-dose (plasma), Days 1 to 2 post-dose (CSF); MAD Groups 7, 8, 9 and 10 Days 0 to 16 post-dose (plasma), Days 14 to 15 post-dose (CSF).

  • • Pharmacokinetic Parameter of maximum plasma concentration (cmax) calculation after single and multiple oral doses of GSM-779690-T

    SAD Groups 1, 2, 3, 6 Days 0 to 7 post-dose (plasma); SAD Groups 4 and 5 Days 0 to 10 post-dose (plasma), Days 1 to 2 post-dose (CSF); MAD Groups 7, 8, 9 and 10 Days 0 to 16 post-dose (plasma), Days 14 to 15 post-dose (CSF).

  • Pharmacokinetic Parameter of time to maximum plasma concentration (tmax) calculation after single and multiple oral doses of GSM-779690-T

    SAD Groups 1, 2, 3, 6 Days 0 to 7 post-dose (plasma); SAD Groups 4 and 5 Days 0 to 10 post-dose (plasma), Days 1 to 2 post-dose (CSF); MAD Groups 7, 8, 9 and 10 Days 0 to 16 post-dose (plasma), Days 14 to 15 post-dose (CSF).

Study Arms (10)

Cohort 01: 20 mg

EXPERIMENTAL

Healthy adult participants receiving a single dose in the SAD study.

Drug: GSM-779690TOther: Placebo

Cohort 02: dose to be determined

EXPERIMENTAL

Healthy adult participants receiving a single dose in the SAD study.

Drug: GSM-779690TOther: Placebo

Cohort 03: dose to be determined

EXPERIMENTAL

Healthy adult participants receiving a single dose in the SAD study.

Drug: GSM-779690TOther: Placebo

Cohort 04: dose to be determined

EXPERIMENTAL

Healthy adult participants receiving a single dose (x2) in the SAD study.

Drug: GSM-779690TOther: Placebo

Cohort 05: dose to be determined

EXPERIMENTAL

Healthy adult participants receiving a single dose (x2) in the SAD study.

Drug: GSM-779690TOther: Placebo

Cohort 06: dose to be determined

EXPERIMENTAL

Healthy adult participants receiving a single dose in the SAD study.

Drug: GSM-779690TOther: Placebo

Cohort 07: dose TBD

EXPERIMENTAL

Healthy adult participants receiving a multiple dose in the MAD study.

Drug: GSM-779690TOther: Placebo

Cohort 08: dose TBD

EXPERIMENTAL

Healthy adult participants receiving a multiple dose in the MAD study.

Drug: GSM-779690TOther: Placebo

Cohort 09: dose TBD

EXPERIMENTAL

Healthy adult participants receiving a multiple dose in the MAD study.

Drug: GSM-779690TOther: Placebo

Cohort 10: dose TBD

EXPERIMENTAL

Healthy older-adult participants receiving a multiple dose in the MAD study.

Drug: GSM-779690TOther: Placebo

Interventions

GSM-779690TDRUG

Opaque capsules for oral consumption.

Cohort 01: 20 mgCohort 02: dose to be determinedCohort 03: dose to be determinedCohort 04: dose to be determinedCohort 05: dose to be determinedCohort 06: dose to be determinedCohort 07: dose TBDCohort 08: dose TBDCohort 09: dose TBDCohort 10: dose TBD
PlaceboOTHER

Opaque capsules for oral consumption.

Cohort 01: 20 mgCohort 02: dose to be determinedCohort 03: dose to be determinedCohort 04: dose to be determinedCohort 05: dose to be determinedCohort 06: dose to be determinedCohort 07: dose TBDCohort 08: dose TBDCohort 09: dose TBDCohort 10: dose TBD

Eligibility Criteria

Age20 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy, cognitively typical, and aged 20-45 years (inclusive).
  • Current Mini Mental State Examination (MMSE) score between 27 and 30 (inclusive) at screening.
  • Able to provide their own written informed consent.
  • Able to read, speak and understand English to ensure compliance with cognitive testing and study visit procedures.
  • Must be ambulatory and be willing to remain domiciled in the clinic for the required study procedures.
  • Contraception requirements:
  • a. Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control (confirmed by the investigator) from enrollment, throughout the study duration, at 1 week after last dose of study treatment, and have a negative pregnancy test result at screening. Highly effective methods of birth control (those that can achieve a failure rate of less than 1% per year when used consistently and correctly) include: (i) Combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal, (ii) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable, (iii) Intrauterine device, (iv) Intrauterine hormone-releasing system, (v) Bilateral tubal occlusion, (vi) Sexual abstinence, ie, refraining from heterosexual intercourse (vii) Vasectomised sexual partner (provided that partner is the sole sexual partner of the WOCBP study participants and that the vasectomized partner has received medical assessment of the surgical success).
  • b. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. The following age-specific requirements apply: (i) Women \< 50 years old will be considered postmenopausal if they have been amenorrhoeic for \>12 months following cessation of exogenous hormonal treatment and FSH levels are in the postmenopausal range (\>40 IU/L). Until FSH is documented to be within menopausal range, the patient should be treated as a WOCBP.
  • (ii) Women \> 50 years old will be considered postmenopausal if they have been amenorrhoeic for \>12 months following cessation of all exogenous hormonal treatment.
  • c. Males with childbearing partners must be willing to practice sexual abstinence or use double-barrier protection during study treatment and until 1 week after the last dose of study treatment.
  • \. Healthy, cognitively typical, aged 60-75 years (inclusive).
  • \. Older participants (Cohort 10) must be living in the community (includes long-term assisted living facilities but excludes long-term care nursing facilities).
  • \. If applicable, older-adult participants (Cohort 10) diagnosed with chronic cardio- or metabolic diseases must have the condition well controlled (in the opinion of the investigator) to include a stable regimen for four (4) weeks prior to Dose Day 1. Some medications are permitted to treat common disorders, such as but not limited to hypertension, type II diabetes, dyslipidemia, and hypothyroidism.
  • \. Participants must have low likelihood of brain amyloid presence based on an amyloid probability score 2 (APS2) of \< 47.5 calculated by PrecivityAD2™ test using the plasma sample collected at screening visit.
  • Participants meeting any of the following criteria must be excluded in the study:
  • +29 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Conditions

Plaque, Amyloid

Condition Hierarchy (Ancestors)

Pathological Conditions, AnatomicalPathological Conditions, Signs and Symptoms

Study Officials

  • Doug Galasko, MD

    University of California, San Diego

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
The active drug and placebo control have the same appearance and weight. The study drug or placebo will be prepared by a licensed pharmacist and dispense the active or placebo capsules to the participants according to the randomization schedule.
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 13, 2025

First Posted

September 4, 2025

Study Start

November 9, 2025

Primary Completion (Estimated)

July 11, 2026

Study Completion (Estimated)

July 11, 2026

Last Updated

January 7, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)