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ATTUNE: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS)

ConditionMethyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexMale
Age2-65
SponsorIonis Pharmaceuticals, Inc.

About this trial

The primary purpose of this study is to evaluate the safety and tolerability of ION440.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Males aged ≥ 2 to ≤ 65 years, depending on specific cohort and group, at the time of informed consent.

Group A: ≥ 8 to ≤ 65 years old

Group B: 2 to 7 years old, inclusive

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.

Disqualifiers

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.

Clinically significant vital sign or ECG abnormality at Screening

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.

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • ION440

    Drug

    ION440 will be administered by intrathecal bolus (ITB) injection.

  • Sham procedure

    Procedure/Surgery

    An LP will be performed with CSF collection but will not be followed by the administration of study treatment by ITB injection.

Treatment groups

48 Participants
are divided into 4 treatment groups
Group A: Cohort 1: ION440 Dose AExperimental treatment 1 intervention
Group B: Cohort 2: ION440 Dose BExperimental treatment 1 intervention
Group C: Cohort 3: ION440 Dose CExperimental treatment 1 intervention
Group D: Sham ProcedureSham comparator 1 intervention

Trial outcomes

Primary outcomes

1

Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Time frame
Up to approximately 36 weeks
2

Part 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Time frame
Baseline up to approximately 36 weeks
3

Part 1: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings

Time frame
Baseline up to approximately 36 weeks
4

Part 1: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments

Time frame
Baseline up to approximately 36 weeks

Secondary outcomes

1

Part 1: Maximum Observed Concentration (Cmax) of ION440 in Plasma

Time frame
Pre-dose and at multiple points post-dose up to Week 36
2

Part 1: Area Under the Concentration-time Curve (AUC) of ION440 in Plasma

Time frame
Pre-dose and at multiple points post-dose up to Week 36
3

Part 1: Plasma Terminal Elimination Half-life (t½) of ION440

Time frame
Pre-dose and at multiple points post-dose up to Week 36
4

Part 1: Trough Concentration (Ctrough) of ION440 in Plasma and CSF

Time frame
Pre-dose and at multiple points post-dose up to Week 36

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ionis Pharmaceuticals, Inc.

Lead sponsor

Source ClinicalTrials.gov
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