Study of CMP-002 in Participants With SYNGAP1-Related Disorder (ASCEND)

A Double-blind, Randomized, Controlled, Multiple Ascending Dose Study of Intrathecally Administered CMP-002 in Participants With SYNGAP1-Related Disorder

The primary purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of CMP-002 in participants with SYNGAP1-related disorder.

Study Overview

• Status: Not yet recruiting
• Conditions: Nervous System Disease
• Intervention / Treatment: Drug: CMP-002; Other: Sham-prick

Detailed Description

ASCEND is a global, Phase 1/2, multicenter, randomized, double-blind (Sponsor-open), controlled, multiple-ascending dose (MAD) study to assess the safety, tolerability, and pharmacokinetics, of CMP-002 in participants with SYNGAP1-related disorder (SRD). The study consists of a Baseline Period in which participants will undergo screening assessments to establish the baseline for clinical study assessments. The Baseline Period is followed by a Treatment Period consisting of 3 planned dose level cohorts wherein each participant will receive 3 doses of CMP-002 administered intrathecally (IT) or a control procedure on Days 1, 29, and 85. Each dose level cohort includes a minimum of 8 participants randomized in a 3:1 ratio (CMP-002: control). Following the completion of Dose 3, participants will be followed for an additional 24 weeks in the Follow-up Period.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: CAMP4 Therapeutics Clinical Trials Information; Phone Number: 617-651-8867; Email: medinfo@camp4tx.com

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Alemán

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent and/or assent, according to local guidelines

• Participant is ≥2 and <18 years of age at the time of informed consent/assent

• Participants must have a clinical diagnosis of a SYNGAP1-related disorder. For entry into the treatment period, genetic confirmation (specifically, of protein truncating mutations in SYNGAP1 exons 5-19) is required. The following mutations in SYNGAP1 exons 5-19 are acceptable:

  1. Frameshift mutations
  2. Nonsense mutations

• Ability to comply with the protocol and trial procedures detailed in the Schedule of Assessments (SoA)

• Participant has phenotype consistent with haploinsufficiency

• Participants must be taking at least one maintenance ASM, have not made changes to ASMs dose or frequency for 6 weeks prior to entering the Baseline Period, and not be planning to change their anti-seizure regimen throughout the study

• For entry into Treatment Period: All maintenance ASMs and interventions for seizures, as well as any cannabinoid-based products, must have been stable (weight-related adjustments are allowed) during the Baseline Period

Exclusion Criteria:

• Participant has an exon 1-4, non-truncating mutation, missense mutations, and microdeletions that include the SYNGAP1 gene
• Participant's prior genetic test indicates a pathogenic or likely pathogenic variant in a gene other than SYNGAP1 (the pathogenic or likely pathogenic variant must be homozygous in cases of known recessive disease)
• Participant's genetic test indicates SYNGAP1 variant of unknown significance (VUS), mosaicism or additional genetic diagnoses
• Participant has a history of central nervous system (CNS) disease (other than epilepsy or SRD), including history of bacterial or viral meningitis or brain malformation
• History of intolerance of IT administration, including intolerance to lumbar puncture
• For entry into the Treatment Period: Participant has a spinal deformity or other condition that may alter the free flow of CSF or has an implanted CSF drainage shunt. Note: Participants with scoliosis or spinal rods are not excluded if, in the judgement of the Investigator, lumbar puncture can be performed and there is free flow of CSF.
• Participant has laboratory results outside of the normal ranges at screening and judged as clinically relevant by the Investigator for liver function (including GGT, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase), kidney function (creatinine, urea), and platelets
• Positive viral serology test results for HIV type 1 or 2 antibodies, hepatitis B surface antigen or hepatitis C virus (HCV) antibody
• Participant has participated in any other interventional clinical study of an investigational gene therapy, or participant is currently participating in or has participated in a clinical study involving an investigational medicinal product within 2 months (or 5 half-lives, whichever is longer) prior to Screening
• Participant is currently using or plans to use unapproved or experimental medicinal products or cannabinoid or cannabidiol or supplemental products, including acetyl-leucine related products
• Participant is using anticoagulants and antiplatelet agents; and is unwilling or unable to discontinue use per standard of care prior to and after the lumbar puncture dosing Day 1
• Participant has any other symptomatology of SRD disease or any disease or disorder, including a clinically significant unstable medical condition, CNS disease (other than epilepsy), or brain malformation, which in the opinion of the Investigator, may either put the participant at risk because of participation in the study including consideration of sedation procedures, may influence the results of the study, or may affect the participant's ability to participate in the study.
• Participant has known hypersensitivity to the excipients of the investigational medicinal product.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CMP-002 Multiple Ascending Dose (MAD); Participants will be administered CMP-002 on Days 1, 29, and 85, and will be followed for 24 weeks after the last dose. Three dose levels will be evaluated.	Drug: CMP-002; CMP-002 is an antisense oligonucleotide that will be administered by IT injection.
Sham Comparator: Sham-prick; Participants will receive the sham-prick procedure on Days 1, 29, and 85, and will be followed for 24 weeks after the last procedure.	Other: Sham-prick; The sham-prick procedure involves no injection/puncture or penetration of the dura, but only a skin prick with a needle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of multiple doses of CMP-002: incidence of adverse events and changes from baseline in clinical laboratory results	Screening to Week 36

Secondary Outcome Measures

Outcome Measure	Time Frame
CSF concentrations of the active drug substance of CMP-002 after multiple doses	Day 1 to Week 36
Plasma PK of the active drug substance of CMP-002 after multiple doses: Cmax	Day 1 to Day 85
Plasma PK of the active drug substance of CMP-002 after multiple doses: AUC(0-24h)	Day 1 to Day 85
Urine PK of the active drug substance of CMP-002: Cmax	Day 1
Urine PK of the active drug substance of CMP-002: AUC(0-24hr)	Day 1

Collaborators and Investigators

• Sponsor: CAMP4 Therapeutics Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: October 30, 2026
• First Submitted That Met QC Criteria: November 6, 2026
• First Posted (Actual): November 13, 2026

Study Record Updates

• Last Update Posted (Actual): November 13, 2026
• Last Update Submitted That Met QC Criteria: November 6, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: SYNGAP1-related disorder
• Additional Relevant MeSH Terms: Nervous System Diseases
• Other Study ID Numbers: SYNG-101; 2026-526220-46-00 (Ctis)

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.: Yes