Study of LHP588 in Subjects With P. Gingivalis-Positive Alzheimer's Disease

May 29, 2026 updated by: Lighthouse Pharmaceuticals, Inc.

A Randomized, Double-Blind, Placebo-Controlled Study of LHP588 in Subjects With P. Gingivalis-Positive Alzheimer's Disease

This study is to test LHP588 in persons who have mild to moderate Alzheimer's disease (AD) who have shown progressive mental decline in the last year and who have P. gingivalis (Pg) infection. P. gingivalis infection has been linked to the development of dementia. LHP588 is designed to target the P. gingivalis bacterium, to potentially help to halt or slow down the progression of AD and its symptoms. A saliva test will be done to determine P. gingivalis infection. Tests for AD include standard questionnaires such as MMSE and a blood test for pTau 217. Treatment will be blinded, meaning the participant and the doctor will not know if the participant is receiving LHP588 or placebo. The total time for participation in the study may be up to 64 weeks. This includes a screening period (to ensure the participant is suitable for the study and the study is suitable for the participant) of up to 12 weeks, a treatment period of up to 48 weeks, and a safety follow-up period of 4 weeks after the last dose of the study drug to check the participant's overall health. Treatment is a once-a-day capsule. Caregiver participation is required. The study requires the participant to visit the study center (with the caregiver) at least 20 times within 64 weeks (this does not include any unplanned visits that may be recommended by the study doctor). In addition, the study doctor or clinic staff will contact the participant via phone at least 1 time.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, double-blind, placebo-controlled study that will assess the efficacy and safety of LHP588 in participants with evidence of P. gingivalis [Pg] infection and Alzheimer's Disease (AD) according to the National Institute on Aging-Alzheimer's Association (NIA-AA) research criteria. Enrolled participants must also have evidence of P. gingivalis infection as determined by polymerase chain reaction (PCR) of saliva oral rinse and clinical evidence of progressive cognitive decline in the last year. The participant should not have other conditions or brain imaging abnormalities that can explain the symptoms of dementia based on prior imaging and the screening magnetic resonance imaging (MRI). Due to the nature of AD, participants must identify a primary caregiver prior to enrollment in the study who will assist the participant with study participation and attend clinic visits.

The study will consist of the following periods: 1) screening period of up to 12 weeks, 2) double-blind treatment period of 48 weeks (including a 2 week up-titration for the high dose arm), and 3) safety follow-up period of 4 weeks.

The screening period will include at least two office visits during which eligibility will be verified. The first screening visit assessments will be limited to only include the Mini-Mental State Examination (MMSE) and a saliva sample collection to assess Pg positivity. The second screening visit will only be scheduled for participants with positive results of Pg infection test and the rest of the screening procedures will be performed. Screening MRI will be performed as the last eligibility verification assessment.

Participants who meet all eligibility criteria will be randomized in a 1:1:1 fashion to receive LHP588 25 mg, LHP588 50 mg, or placebo, orally, once daily (QD) in a fasted state (at least one hour before or two hours after a meal) for 48 weeks. Dosing should be done at approximately the same time each day. Blood samples for pharmacokinetics levels and biomarkers will be collected during selected visits.

Evaluations will be conducted according to the schedule of assessments and will include: Medical history, physical examination, height, weight, saliva rinse for verification of Pg infection, blood for pharmacokinetic analysis, safely laboratory measures, electrocardiogram, and cognitive and functional scale assessments such as ADAS Cog, administered periodically.

After completion of study treatment, participants will continue to be monitored for 4 weeks and will have a phone call to assess safety at Week 50 and will return for the Safety Follow-up Visit (Week 52).

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Recruiting
        • Banner Alzheimer's Institute
        • Principal Investigator:
          • Allison Perrin, MD
        • Contact:
      • Phoenix, Arizona, United States, 85013
        • Recruiting
        • Barrow Neurological Institute
        • Principal Investigator:
          • Anna Burke, MD
        • Contact:
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • Clinical Endpoints
        • Contact:
        • Principal Investigator:
          • Allan Block, MD
    • California
      • Oakland, California, United States, 94609
        • Not yet recruiting
        • Oakland Clinical Research
        • Contact:
        • Principal Investigator:
          • Richard Parenteau, MD
      • Orange, California, United States, 92866
        • Recruiting
        • ATP Clinical Research, Inc.
        • Principal Investigator:
          • Gustavo Alva, MD
        • Contact:
      • Riverside, California, United States, 92506
        • Not yet recruiting
        • Riverside Clinical Research
        • Contact:
        • Principal Investigator:
          • Cydney Osano, MD
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Not yet recruiting
        • CenExel Denver, CO
        • Contact:
        • Principal Investigator:
          • Katherine Coerver, MD, PhD
    • Florida
      • Atlantis, Florida, United States, 33462
        • Recruiting
        • JEM Research Institute
        • Principal Investigator:
          • Linda Pao, MD
        • Contact:
      • Delray Beach, Florida, United States, 33445
      • Fort Myers, Florida, United States, 33912
        • Recruiting
        • Neuropsychiatric Research Center of Southwest Florida
        • Principal Investigator:
          • Jennifer Springer, MD
        • Contact:
      • Orlando, Florida, United States, 32832
      • Pensacola, Florida, United States, 32502
        • Recruiting
        • Anchor Neuroscience
        • Contact:
        • Principal Investigator:
          • Kevin Groom, PhD
      • Stuart, Florida, United States, 34997
        • Recruiting
        • Alzheimer's Research and Treatment Center - Stuart
        • Principal Investigator:
          • Adam Falchook, MD
        • Contact:
      • Wellington, Florida, United States, 33414
        • Recruiting
        • Alzheimer's Research and Treatment Center - Wellington
        • Contact:
        • Principal Investigator:
          • Annet Falchook, MD
    • Georgia
      • Columbus, Georgia, United States, 31909
        • Recruiting
        • Columbus Memory Center
        • Contact:
        • Principal Investigator:
          • Mark Stafford, DO
      • Gainesville, Georgia, United States, 30501
        • Recruiting
        • Center for Advanced Research & Education Flourish-Gainesville
        • Contact:
        • Principal Investigator:
          • Chris Recknor, MD
      • Savannah, Georgia, United States, 31405
        • Not yet recruiting
        • Cenexel Savannah GA
        • Principal Investigator:
          • Michael Mobley, MD
        • Contact:
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Not yet recruiting
        • Ascension Via Christi Research
        • Principal Investigator:
          • Paul Murphy, MD
        • Contact:
    • Louisiana
      • Metairie, Louisiana, United States, 70006
        • Recruiting
        • Tandem Clinical Research - Metairie
        • Principal Investigator:
          • Angela Traylor, MD
        • Contact:
    • Maryland
      • Pikesville, Maryland, United States, 21208
    • Massachusetts
      • Boston, Massachusetts, United States, 02116
        • Recruiting
        • Adams Clinical Boston
        • Principal Investigator:
          • Darin Dougherty, MD
        • Contact:
      • Plymouth, Massachusetts, United States, 02360
        • Recruiting
        • Headlands Research-EMA
        • Contact:
        • Principal Investigator:
          • Kinan Hreib, MD, PhD
      • Watertown, Massachusetts, United States, 02472
        • Recruiting
        • Adams Clinical Watertown
        • Principal Investigator:
          • Stephanie Rutrick, MD
        • Contact:
    • Mississippi
      • Hattiesburg, Mississippi, United States, 39401
        • Recruiting
        • Neurological Research Center - Hattiesburg Clinic
        • Contact:
        • Principal Investigator:
          • Ronald Schwartz, MD
    • Missouri
      • Chesterfield, Missouri, United States, 63005
    • New Jersey
      • Toms River, New Jersey, United States, 08755
        • Recruiting
        • CenExel Research - Toms River
        • Principal Investigator:
          • Arun Singh, MD
        • Contact:
          • Anna Brocco
          • Phone Number: 3510 732-341-9500
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Recruiting
        • IMA Evaluations
        • Contact:
        • Principal Investigator:
          • Daniel Collins, MD
    • New York
      • Albany, New York, United States, 12208
        • Recruiting
        • Alzheimer's Disease Research Center
        • Principal Investigator:
          • Richard Holub, MD
        • Contact:
      • New York, New York, United States, 10029
        • Recruiting
        • Adams Clinic Harlem
        • Contact:
        • Principal Investigator:
          • Rachel Noone, MD
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Adams Clinical Bronx
        • Principal Investigator:
          • Shama Farooq, MD
        • Contact:
    • Ohio
      • Dayton, Ohio, United States, 45459
        • Recruiting
        • NDx Clinical Research
        • Principal Investigator:
          • Joel Vandersluis, MD
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97210
    • Tennessee
      • Nashville, Tennessee, United States, 37204
        • Recruiting
        • K2 Medical Research Nashville LLC
        • Contact:
        • Principal Investigator:
          • Joshua Lennon, MD
    • Texas
      • Dallas, Texas, United States, 75216
        • Recruiting
        • Kerwin Research Center, LLC - Oak Cliff
        • Contact:
        • Principal Investigator:
          • Zaid Shah, DO
      • Dallas, Texas, United States, 75231
        • Recruiting
        • Kerwin Research Center, LLC in Texas
        • Principal Investigator:
          • Alka Khera, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • Re:Cognition Health - Houston
        • Principal Investigator:
          • Avni Kapadia, MD
        • Contact:
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia Adult Neurology
        • Contact:
        • Principal Investigator:
          • Carol Manning, PhD
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Re-Cognition Health Fairfax
        • Contact:
        • Principal Investigator:
          • Raymond S Turner, MD, PhD
    • Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • AD according to the National Institute on Aging-Alzheimer's Association criteria.
  • MMSE scores corresponding to mild and moderate AD.
  • Saliva rinse sample positive for P. gingivalis.
  • Plasma pTau217 above cutoff.
  • Subject and caregiver have provided full written informed consent.
  • Background symptomatic therapy with acetylcholinesterase inhibitors, and/or memantine, are allowed if the dose has been stable for 90 days and no changes are planned during the study.
  • Modified Hachinski score ≤4 at screening.

Exclusion Criteria:

  • History of cancer requiring systemic therapy in last 5 years.
  • Evidence of a clinically significant, unstable cardiovascular, pulmonary, renal, hepatic, gastrointestinal, neurologic, or metabolic disease within 6 months prior to screening.
  • Unstable angina, uncompensated and/or symptomatic congestive heart failure (Grade 2 or higher on the New York Heart Association scale) or myocardial infarction within 6 months.
  • Acute or poorly controlled blood pressure >180 mmHg systolic or >100 mmHg diastolic at screening visit.
  • History or current evidence of major neurological or psychiatric illness such as schizophrenia, bipolar disorder, Parkinson's Disease, other.
  • Currently being treated with anti-amyloid beta antibodies or other disease-modifying treatments for dementia.
  • Other criteria in the Investigator's judgement that may interfere with the ability to participate in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo capsule, once daily, for 48 weeks
Drug: Placebo Drug
Placebo, once daily
Experimental: LHP588 25 mg
One 25 mg capsule, once daily, for 48 weeks
Drug: LHP588
25 mg, once dialy
Other Names:
  • Low dose
Drug: LHP588
50 mg, once daily
Other Names:
  • High dose
Experimental: LHP588 50 mg
Two 25 mg capsules, once daily, for 48 weeks
Drug: LHP588
25 mg, once dialy
Other Names:
  • Low dose
Drug: LHP588
50 mg, once daily
Other Names:
  • High dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in ADAS-Cog11 to the end of treatment period (at Week 40 - 48)
Time Frame: 40 - 48 weeks
ADAS-COG11 is the Alzheimer's Disease Assessment Scale-Cognitive Subscale 11
40 - 48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in CDR-SB to the end of treatment (at Week 40-48)
Time Frame: 40 - 48 weeks
CDR-SB is the Clinical Dementia Rating-Sum of Boxes
40 - 48 weeks
Change from baseline in ADCS-ADL to the end of treatment (at Week 40-48)
Time Frame: 40 - 48 weeks
ADCS-ADL is the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living
40 - 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lighthouse Pharmaceuticals, Inc.

Investigators

  • Study Director: Stephen Dominy, MD, Lighthouse Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 17, 2025

Primary Completion (Estimated)

January 31, 2029

Study Completion (Estimated)

March 15, 2029

Study Registration Dates

First Submitted

February 21, 2025

First Submitted That Met QC Criteria

February 21, 2025

First Posted (Actual)

February 26, 2025

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LHP588-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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