Pediatric SDLT CNS Disorders
Conditions
Brief summary
This study is being conducted to evaluate individualised antisense oligonucleotides (ASOs) in participants with severely debilitating, life threatening (SDLT) central nervous system (CNS) conditions caused by unique genetic variants amenable to correction by an ASO.
Detailed description
This phase 1/2 multicentre, open-label, within-participant dose escalation clinical trial is designed to evaluate individualised antisense oligonucleotides (ASOs) in participants aged 1 year or older with severely debilitating, life threatening (SDLT) central nervous system (CNS) conditions caused by unique genetic variants amenable to correction by an ASO. The trial consists of two parts: Part A: a 30-day Screening period and a minimum 4-week Run-in period followed by Part B: a 48-week Treatment period and Safety Follow-up. For each part, the investigator will determine if the participant is appropriate for participation based on disease stage, rate of disease progression, and likelihood of benefit from ASO treatment at the time that the ASO is available.
Interventions
DRUGIndividualized ASO
Individualized ASO
Sponsors
EveryONE Medicines Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The first participant receiving the individualised ASO, must be between 1 and 17 years of age (inclusive) at the time they receive their first ASO dose. 2. The CNS condition is severely debilitating and/or life threatening. 3. The identified genetic variant is unique. 4. The identified genetic variant is considered the underlying cause of disease. 5. The identified genetic variant is amenable to correction by an ASO. 6. In the opinion of the investigator, the disease is at a stage that, if halted or slowed by treatment with the individualised ASO, has a reasonable chance to improve the participant's overall disease burden/impact on quality of life. 7. In the opinion of the investigator, participant, and/or the participant's legally authorised representative, existing therapies have not resulted in meaningful benefit.
Exclusion criteria
1. Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological, or haematological disease or condition other than the primary disease for which the individualised ASO is being developed that in the opinion of the Investigator could affect patient safety or interfere with study outcomes. 2. Any contraindication to brain MRI scans. 3. Any contraindication to sedation or anaesthesia. 4. Any contraindication to lumbar punctures or IT infusions. 5. Treatment with another ASO within 24 weeks of Screening. 6. Treatment with any gene replacement therapy at any time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | 48 Weeks | Treatment-related incidence and severity of adverse events (AEs), including any unfavorable and unintended signs such as abnormal laboratory or test findings |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) | Plasma collected pre-dose and at .5, 1, 2, 6, 24, and 48 hour post-infusion | Estimates of ASO maximum plasma concentration (Cmax) |
| Area Under the Plasma Concentration-time Curve (AUC) | Plasma collected Pre-dose and .5, 1, 2, 6, 24, and 48 hours post infusion | Area under the plasma concentration-time curve (AUC) from time zero to infinity following a dosing of study drug. It is an integrated measure of study drug plasma exposure. |
| Plasma Half-life (T1/2) | Plasma collected pre-dose and .5, 1, 2, 6, 24, and 48 hours post infusion | Apparent terminal plasma half-life (T1/2) is the amount of time for plasma concentrations to decline by 50%. |
Countries
United Kingdom
Outcome results
None listed