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

March 11, 2026 updated by: n-Lorem Foundation

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children (SickKids)

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Open Label
Drug: nL-PACS1-001
Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Baseline to 24 months
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
Baseline to 24 months
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
Baseline to 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Baseline to 24 months
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)
Baseline to 24 months
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
Baseline to 24 months
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
Baseline to 24 months
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)
Baseline to 24 months
Safety and Tolerability
Time Frame: Baseline to 24 months
Incidence and severity of treatment-emergent adverse events (AEs) post nL-GPACS1-001 administration
Baseline to 24 months
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)
Baseline to 24 months
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)
Baseline to 24 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Baseline to 24 months
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
Baseline to 24 months
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
Baseline to 24 months
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)
Baseline to 24 months
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
Baseline to 24 months
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
Baseline to 24 months
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)
Baseline to 24 months
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
Baseline to 24 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
n-Lorem Foundation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Hospital for Sick Children (SickKids)

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 11, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NLF-HC-0001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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