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

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.