LIFE-DSR-Biomarker Sub-study of Biomarkers in Down Syndrome Related Alzheimer's Disease (DS-AD)

NCT06860373 | Terminated Phase 3 FDA Drug

• 1 other identifier: LIFE-DSR-BIO DS-AD
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is an optional sub-study that will enroll participants from the LIFE-DSR parent protocol. Participants will undergo assessments at two timepoints, including: additional blood samples for PBMC and RNA extraction, as well as a lumbar puncture for collection of CSF, and/or MRI and tau PET imaging. Sub-study visits will be scheduled around a similar calendar-day as the parent protocol study visits (e.g., Month (M) 0 (M0) and M16, or M16 and M32).

Conditions

Down Syndrome

Outcome Measures

Primary Outcomes (2)

• Primary Outcome Measure to establish a biobank specifically for DS participants

  CSF AD biomarkers measured longitudinally at approximately Month 0 and Month 16 or Month 16 and Month 32. Establish a biobank specific to DS to receive, store and distribute biospecimens supporting future Omics, biomarker analyses, epigenetic studies, and genotyping. Biomarker candidates will be determined when the study ends and may include primary analytes such as AB42, AB40, AB42/40 ratio, t-tau, p-tau, NfL. Evaluate prespecified CSF biomarkers using technically validated immunoassays on the Quanterix, Mesoscale and Abcam Fireplex Cytokine assay platforms. Biomarker candidates will be determined when the study ends and may include primary analytes such as AB42, AB40, AB42/40 ratio, sAPP, sAPPB, t-tau, p-tau, soluble-TREM2, NfL, GFAP, UCHL1, Tau.

  Month 0 and Month 16 or Month 16 and Month 32

• Primary Outcome to ascertain the degree and distribution of tau pathology in DS as a function of age using tau PET

  Burden of total and regional tau deposition, relative to baseline, as measured by \[18F\]MK-6240 uptake. This outcome will provide information regarding: Expected rates of change given baseline amyloid and tau burden, The sample sizes required to detect a reduction in the rate of accumulation at different stages of AD, and Homogeneity and heterogeneity in tau spatial distribution at different stages of AD progression. Correlate the tau PET imaging data with the cognitive, behavioral, functional assessments and medical history data collected in the LIFE-DSR parent protocol to better establish the stage of AD for each participant.

  Month 0 and Month 16 or Month 16 and Month 32

Secondary Outcomes (1)

• Secondary Outcome is to increase knowledge of biomarkers of interest in DS-AD clinical progression and perform deep immunophenotyping of PBMC and plasma samples.

  Month 0 and Month 16 or Month 16 and Month 32

Other Outcomes (1)

• Exploratory Outcome - Biomarkers Comparisons

  through study completion, an average of 2 years

Study Arms (1)

Radiotracer [18F]MK-6240

OTHER

In this sub-study, participants will have two \[18F\]MK-6240 tau PET scans. Participants will undergo administration of \[18F\]MK-6240 to detect the presence of tau in the brain. The applied \[18F\]MK-6240 radioactive dose will be approximately 5 mCi (185 MBq) ± 20%. The mass dose will not exceed 20 µg. This is the only arm.

Biological: [18F]MK-6240

Interventions

[18F]MK-6240 BIOLOGICAL

\[18F\]MK-6240 will be synthesized, purified, and formulated at the local radiochemistry synthesis laboratory and will be administered as a sterile, pyrogen-free solution by IV injection.

Radiotracer [18F]MK-6240

Eligibility Criteria

• Age: 35 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The participant must be currently enrolled in the LIFE-DSR parent protocol.
• The adult with DS must be age 35 to 55 years.
• Both the participant, or LAR, and their caregiver must be able to understand and be willing to provide consent. The LAR will sign the informed consent. The participant will sign the informed consent or assent.
• Both the participant, or LAR, and their caregiver must be willing to comply with the scheduled visits and scheduled assessments.
• Agreement of caregiver and clinician the participant can cooperate with protocol tasks.

You may not qualify if:

• Participants meeting any of these criteria are excluded from the LP portion of the sub-study.
• Assessment (per medical history, physical exam, vital signs or other clinically relevant measure or circumstance) which, in the opinion of the site PI, makes the participant unsuitable for participation in this study.
• Evidence for raised intracranial pressure. Examples include papilledema on physical exam or CNS lesion with mass effect.
• Presence of lower spinal malformations, prior lumbosacral spinal surgery, local infection, or other abnormalities that would exclude lumbar puncture.
• Allergy to Lidocaine (xylocaine) or its derivatives.
• Evidence or history of significant active bleeding or coagulation disorder, or use of anticoagulant medications such as coumadin, heparin, thrombin inhibitors (e.g., dabigatran) or factor Xa inhibitors (e.g., apixaban).
• Previous or ongoing treatment with aducanumab (AduhelmTM) OR any anti-amyloid OR any anti-tau antibody OR investigational treatment within the previous 30-calendar days of this sub-study baseline LP. Treatment with AduhelmTM is permitted in the LIFE-DSR parent protocol but precludes participation in this LP sub-study.
• Participants meeting any of these criteria are excluded from the imaging portion of the sub-study.
• Contraindication to MRI or PET scans, evidenced by presence or history of any significant or uncontrolled medical condition which, in the opinion of the Investigator, would increase the potential risk to the study participant (e.g., history of CNS infection, history of exposure to CNS toxin, epilepsy, sensitivity to flashing lights, pacemaker).
• Participants in whom MRI is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord or cochlear implant. Dental fillings do not present a risk for MRI.
• Suffers from claustrophobia, inability to tolerate confined spaces, or prior failed experience completing MRI scans or blood draws.
• Positive pregnancy test or currently breast-feeding.
• Previous or ongoing treatment with aducanumab (AduhelmTM) OR any anti-amyloid OR any anti-tau antibody OR investigational treatment within the previous 30-calendar days of this sub-study baseline PET. Treatment with AduhelmTM is permitted in the LIFE-DSR parent protocol but precludes participation in this imaging sub-study.

Sponsors & Collaborators

• LuMind IDSC Foundation: lead

Study Sites (1)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: There is no masking for this study.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2024
• First Posted: March 6, 2025
• Study Start: June 27, 2023
• Primary Completion: April 17, 2024
• Study Completion: April 17, 2024
• Last Updated: March 6, 2025

Record last verified: 2024-06

Locations

US (1)