New hope for rare genetic disorder: drug ION440 enters human trials

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Key Inclusion criteria for Part 1: 1. Males aged ≥ 2 to ≤ 65 years, depending on specific cohort and group, at the time of informed consent. 1. Group A: ≥ 8 to ≤ 65 years old 2. Group B: 2 to 7 years old, inclusive 2. Participant has at least one parent or caregiver ≥ 18 years old capable of providing informed consent and able to comply with all study requirements and activities. 3. Participant has a documented diagnosis of MDS with genetic confirmation of MECP2 duplication. 4. Is currently receiving stable doses of concomitant medications for at least 1 month prior to screening. 5. Able to complete all study procedures, measurements and visits to support primary and secondary endpoints, in the opinion of the Investigator. Key Exclusion criteria for Part 1: 1. Documented diagnosis of severe MECP2 duplications including terminal duplication and/or translocation or MECP2 triplication OR clinical features associated with severe variant structure including (a) onset of seizures prior to age 5 (for those aged 5 and above at signing of ICF), (b) oxygen dependence, (c) microcephaly, IF MECP2 genetic structure information is unavailable. 2. Clinically significant vital sign or ECG abnormality at Screening 3. Known brain or spinal disease that would interfere with the LP procedure, or CSF circulation or presence of other factors would affect the safety of the LP procedure. 4. Has any concomitant disease or condition or circumstance, or any finding at Screening that, in the opinion of the Investigator, makes the participant unsuitable for enrollment or that could interfere with the conduct of the study or that would pose an unacceptable risk to the participant in this study. 5. Treatment with an investigational drug, biological agent, or device within 30 days of Screening, or 5 half-lives of investigational agent, whichever is longer. 6. Previous treatment with an oligonucleotide (including siRNA) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received (this exclusion does not apply to vaccines - both mRNA and viral vector vaccines are allowed including COVID-19). For centrally administered ASOs, a minimum of 12 months washout is required irrespective of the number of doses received. 7. Currently enrolled in a clinical trial of an investigational agent or device or has used any investigational agent or device within 5 half-lives of investigational agent, whichever is longer. 8. Has a history of gene therapy or cell transplantation or any other experimental brain surgery. 9. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Baseline (Day 1). 10. Has experienced Status Epilepticus in the past 6 months. Key Inclusion criteria for Part 2: 1. Participants in ION440-CS1, Part 1/MAD who received at least one dose of Study Drug /Sham in Part 1/MAD, missed no more than 1 study visit, and attended the Follow Up visit (Visit 6). 2. All inclusion criteria in Part 1/MAD apply (participants will not be required to undergo new Screening bloodwork). Key Exclusion criteria for Part 2: 1\. Has developed any concomitant disease (e.g., gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or circumstance, or any finding during Part 1/MAD that, in the opinion of the Investigator, makes the participant unsuitable for continued treatment (e.g., could interfere with the conduct of the study or that would pose an unacceptable risk to the participant in this study).