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NCT Number: NCT07474298

Personalized Antisense Oligonucleotide for A Single Participant With PACS1 Gene Mutation Associated With Schuurs-Hoeijmakers Syndrome (SHMS)

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug intended for a single participant with Schuurs-Hoeijmakers syndrome (SHMS) due to a pathogenic, de novo, heterozygous missense gain-of-function mutation in PACS1

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Key information

Conditions

Schuurs-Hoeijmakers Syndrome

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

The Hospital for Sick Children (SickKids)

Toronto, Ontario, M5G 1X8, Canada

About this study

This is an interventional study to evaluate the safety and efficacy of treatment with an individualized antisense oligonucleotide (ASO) treatment in a single participant with SHMS due to a pathogenic, de novo, heterozygous missense gain-of-function mutation in PACS1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Informed consent/assent provided by the participant's parent(s) or legally authorized representative(s)
  • Ability to travel to the study site and adhere to study-related follow-up examinations and/or procedures and provide access to participant's medical records
  • Genetically confirmed SHMS due to PACS1 gene mutationc.607C>T (p.Arg203Trp)

Exclusion criteria

  • Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures
  • Participation in another investigational trial within 3 months of study enrollment or planned participation during the 24-month trial

Treatment and study plan

nL-PACS1-001

Drug

Personalized antisense oligonucleotide

Primary outcomes

  1. Communication Ability

    Time frame: Baseline to 24 months

    Change in communication ability from baseline to 6-, 12-, 18-, and 24-months post nL-PACS1-001 administration as measured by Observer-Rated Communication Ability (ORCA) overall T-score

  2. Communication Ability

    Time frame: Baseline to 24 months

    Change in communication ability from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Vineland Adaptive Behavior Scales - Third Edition (Vineland-3) growth scale values (GSVs) for Expressive Language and Receptive Language subdomains

  3. Communication Ability

    Time frame: Baseline to 24 months

    Change in communication ability from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4) Expressive and Receptive Language domains

Secondary outcomes

  1. Fine Motor Skills

    Time frame: Baseline to 24 months

    Change in communication ability from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Vineland Adaptive Behavior Scales - Third Edition (Vineland-3) Fine Motor Subdomain Growth Scale Values (GSVs)

  2. Fine Motor Skills

    Time frame: Baseline to 24 months

    Change in fine motor skills from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4) Fine motor domain

  3. Fine Motor Skills

    Time frame: Baseline to 24 months

    Change in fine motor skills from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Hammersmith Infant Neurological Examination (HINE) overall score

  4. Fine Motor Skills

    Time frame: Baseline to 24 months

    Change in fine motor skills every 28 days for 24-months post nL-PACS1-001 administration as measured by Early Motor Questionnaire (EMQ)

  5. Safety and Tolerability

    Time frame: Baseline to 24 months

    Incidence and severity of treatment-emergent adverse events (AEs) post nL-GPACS1-001 administration

  6. Incidence of Treatment-Emergent Abnormalities in Physical Exam [Safety and Tolerability]

    Time frame: Baseline to 24 months

    Changes post nL-PACS1-001 administration in physical examination (changes in appearance, skin, neck, ears, nose, throat, heart/lungs, abdomen, lymph nodes, and extremities compared to baseline)

  7. Incidence of Treatment-Emergent Abnormalities in Neurological Exam [Safety and Tolerability]

    Time frame: Baseline to 24 months

    Changes post nL-PACS1-001 administration in neurological examination (changes in mental status, gait, cerebellar, cranial nerve, motor, reflex, and sensations compared to baseline as assessed by treating physician)

  8. Incidence of Treatment-Emergent Abnormalities in Safety Labs (CSF, chemistry, hematology, coagulation, and urinalysis) [Safety and Tolerability]

    Time frame: Baseline to 24 months

    Emergent abnormalities in laboratory analyses (results outside of normal range for CSF, chemistry, hematology, coagulation, and urinalysis)

Other outcomes

  1. Cognition and Behavior and Socialization

    Time frame: Baseline to 24 months

    Change in cognition, behavior, and socialization from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Repetitive Behavior Scale - Revised (RBS-R)

  2. Cognition and Behavior and Socialization

    Time frame: Baseline to 24 months

    Change in cognition, behavior, and socialization from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Vineland Adaptive Behavior Scales - Third Edition (Vineland-3) Fine Motor Subdomain Growth Scale Values (GSVs), Daily Living and Socialization Domain GSVs for Community, Domestic and Personal Subdomains and Coping Skills, Play and Leisure and Interpersonal Relationships Subdomains

  3. Cognition and Behavior and Socialization

    Time frame: Baseline to 24 months

    Change in cognition, behavior, and socialization from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4) Cognition Domain

  4. Seizures

    Time frame: Baseline to 24 months

    Change in frequency of clinical seizures from baseline to 6-, 12-, 18-, and 24-months post nL-PACS1-001 administration as measured by spike counts during sleep per unit time during 24-hour overnight clinical Electroencephalography (EEG)

  5. Seizures

    Time frame: Baseline to 24 months

    Change in frequency of clinical seizures from baseline to 6-, 12-, 18-, and 24-months post nL-PACS1-001 administration as measured by seizure diary

  6. Sleep and Drooling

    Time frame: Baseline to 24 months

    Change in sleep and drooling every 28 days from baseline to 24-months post nL-PACS1-001 administration as measured by Measure Your Own Medical Profile-2 (MYOMP-2) targets of drooling and sleep

  7. Sleep and Drooling

    Time frame: Baseline to 24 months

    Change in sleep and drooling from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Brief Infant Sleep Questionnaire (BISQ)

  8. Cerebrospinal Fluid (CSF) Composition

    Time frame: Baseline to 24 months

    Change in composition of CSF from baseline to 6-, 12-, 18-, and 24- months post nL-PACS1-001 administration as assessed by cerebrospinal fluid analysis

Sponsors and collaborators

Lead sponsor

n-Lorem Foundation

Other

Collaborators

  • The Hospital for Sick Children

Registry information

Official study title

An Open-label Single Center Study of an Experimental Antisense Oligonucleotide Treatment of a Participant With Schuurs-Hoeijmakers Syndrome Due to PACS1 Genetic Mutation

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Mar 16, 2026
Registry last updated
Mar 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.