BridgeMD
A Phase 1-2, Double-Blind, MAD Study of ION440 in MDS
EU CTIS ID: 2023-507192-22-00
What this study is testing
To assess the safety and tolerability of ION440 (Part 1 and 2)
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Part 1: Males aged ≥ 2 to ≤ 65 years, depending on specific cohort and group, at the time of informed consent. − Group A: ≥ 8 to ≤ 65 years − Group B: 2 to 7 years, inclusive
- Part 1: Participant has at least one parent or caregiver ≥ 18 years of age capable of providing informed consent (signed and dated) and able to attend all scheduled study visits and provide feedback regarding the participant’s symptoms and performance as described in the protocol, and able to comply with all study requirements and activities
- Part 1: Participant has a documented diagnosis of MDS, with genetic confirmation of MECP2 duplication.
- Part 1: Able to complete all study procedures, measurements and visits to support primary and secondary endpoints, and the caregiver/participant has adequately supportive psychosocial circumstances, in the opinion of the Investigator.
- Part 1: Is currently receiving stable doses of concomitant medications for at least 1 month prior to Screening.
- Part 2: 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 Followup visit (Visit 6).
You likely can't join if
- Part 1: Confirmed (by repeat measurement) clinically significant vital sign or ECG abnormality at Screening including: a. Heart rate (HR) < 45 beats per minute b. QTcF > 450 milliseconds c. Blood pressure exceeding the 95th percentile for age, sex, and height plus 12 mmHg, or blood pressure meeting hypertension diagnostic criteria for children per European Society of Hypertension (ESH) guidelines for children and adolescents, or blood pressure > 140/90 mmHg d. Blood pressure below the 5th percentile for age, sex, and height per ESH guidelines for children and adolescents.
- Part 2: 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).
- Part 1: Documented diagnosis of severe MECP2 duplication including terminal duplication and/or translocation or MECP2 triplication OR clinical features associated with severe variant structure including (a) onset of seizures prior to aged 5 years (for those 5 years and above at signing of ICF), (b) oxygen dependence, and (c) microcephaly, IF MECP2 genetic structure information is unavailable.
- Part 1: 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.
- Part 1: 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
- Part 1: Treatment with an investigational drug, biological agent, or device within 30 days of Screening, or 5 half-lives of investigational agent, whichever is longer.
See the full eligibility criteria
Who can join
- Part 1: Males aged ≥ 2 to ≤ 65 years, depending on specific cohort and group, at the time of informed consent. − Group A: ≥ 8 to ≤ 65 years − Group B: 2 to 7 years, inclusive
- Part 1: Participant has at least one parent or caregiver ≥ 18 years of age capable of providing informed consent (signed and dated) and able to attend all scheduled study visits and provide feedback regarding the participant’s symptoms and performance as described in the protocol, and able to comply with all study requirements and activities
- Part 1: Participant has a documented diagnosis of MDS, with genetic confirmation of MECP2 duplication.
- Part 1: Able to complete all study procedures, measurements and visits to support primary and secondary endpoints, and the caregiver/participant has adequately supportive psychosocial circumstances, in the opinion of the Investigator.
- Part 1: Is currently receiving stable doses of concomitant medications for at least 1 month prior to Screening.
- Part 2: 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 Followup visit (Visit 6).
- Part 2: All inclusion criteria in Part 1/MAD apply (participants will not be required to undergo Screening blood collections additional to those scheduled on Part 1/MAD Visit 6 [Day 253]).
What rules you out
- Part 1: Confirmed (by repeat measurement) clinically significant vital sign or ECG abnormality at Screening including: a. Heart rate (HR) < 45 beats per minute b. QTcF > 450 milliseconds c. Blood pressure exceeding the 95th percentile for age, sex, and height plus 12 mmHg, or blood pressure meeting hypertension diagnostic criteria for children per European Society of Hypertension (ESH) guidelines for children and adolescents, or blood pressure > 140/90 mmHg d. Blood pressure below the 5th percentile for age, sex, and height per ESH guidelines for children and adolescents.
- Part 2: 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).
- Part 1: Documented diagnosis of severe MECP2 duplication including terminal duplication and/or translocation or MECP2 triplication OR clinical features associated with severe variant structure including (a) onset of seizures prior to aged 5 years (for those 5 years and above at signing of ICF), (b) oxygen dependence, and (c) microcephaly, IF MECP2 genetic structure information is unavailable.
- Part 1: 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.
- Part 1: 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
- Part 1: Treatment with an investigational drug, biological agent, or device within 30 days of Screening, or 5 half-lives of investigational agent, whichever is longer.
- Part 1: 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.
- Part 1: Has experienced Status Epilepticus in the past 6 months.
- Part 1: Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to BL (Day 1).
- Part 1: Has a history of gene therapy or cell transplantation or any other experimental brain surgery.
The study team makes the final eligibility decision.
Where it's taking place
- United States
- Canada
- United Kingdom
- Australia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling male, 0-17 years, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; Canada; United Kingdom; Australia. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.