X-TOLE4

12 evidence topics · 3 sources

Objective

Open-label extension of the Phase 3 epilepsy trials

“This is an Open Label Extension study of the following Phase 3 clinical studies: XPF-010-301 (X-TOLE2), XPF-010-302 (X-TOLE3), and XPF-010-303 (X-ACKT). This study will evaluate the long-term safety, tolerability, PK, and efficacy of XEN1101 in subjects with FOS or PGTCS for the treatment of seizures for up to 6 years. Subjects who successfully completed and did not terminate early from one of the antecedent studies (X-TOLE2, X-TOLE3, or X-ACKT) are eligible to participate in X-TOLE4.” (opens the source at this quote in a new tab)

Extension available to Phase 3 completers

“Upon completion of the DBP in the Phase 3 epilepsy studies, eligible patients may enter an open-label extension (OLE) study for up to six years.” (opens the source at this quote in a new tab)

Location and study date

Summary: identifiers, dates, and enrollment

The registry record for NCT05718817 gives XPF-010-304 as the sponsor protocol number and X-TOLE4 as the acronym, with an overall status of enrolling by invitation. The actual study start date was 25 April 2023, with estimated primary completion in April 2033 and estimated study completion in June 2033. Estimated enrollment is 880 participants, with a minimum age of 12 years.

Study design

Duration and visit schedule

“Following enrollment into X-TOLE4, subjects will undergo a treatment period of up to 6 years, during which there will be a visit at 2-, 4-, and 13-weeks post-entry, with subsequent visits occurring at 13-week intervals during the first year, and then at 26-week intervals (with a telephone call in between) until dosing is completed.” (opens the source at this quote in a new tab)

Long-term objectives

“This study will evaluate the long term safety, tolerability, pharmacokinetics (PK), and efficacy of XEN1101 in subjects with Focal Onset Seizures (FOS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) for the treatment of seizures for up to 6 years.” (opens the source at this quote in a new tab)

Eligibility criteria

Eligibility limited to completers of the antecedent Phase 3 studies

“Subjects who successfully completed and did not terminate early from one of the antecedent studies (X-TOLE2, X-TOLE3, or X-ACKT) are eligible to participate in X-TOLE4.” (opens the source at this quote in a new tab)

Treatment

Dosing and seizure diary compliance

“Subjects will be instructed to orally take XEN1101 once daily (QD) with an evening meal. Subjects will be expected to keep a daily seizure eDiary with a minimum of 80% compliance for the duration of the extension study (reporting on ≥80% of days between visits).” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using percent change in monthly seizure rate as a secondary endpoint

Outcome measures in the extension

“To assess the safety and tolerability of XEN1101” (opens the source at this quote in a new tab)
“Percent change in monthly seizure rate recorded at baseline (in the antecedent studies) compared to each 4-week assessment period in the treatment period in X-TOLE4.” (opens the source at this quote in a new tab)
“Proportion of responders (subjects experiencing ≥50% reduction in seizure frequency from baseline) in each consecutive 4-week assessment period of the treatment period of the OLE study.” (opens the source at this quote in a new tab)
“Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Summary: planned enrollment

The registry record gives an estimated enrollment of 880 participants drawn from the completers of X-TOLE2, X-TOLE3, and X-ACKT. Of the 332 participants who completed the X-TOLE2 double-blind period, 322 entered the open-label extension study.

Description of analysis sets

No evidence found.

Results

Participant disposition

Entry from the X-TOLE2 double-blind period

“Of the 332 participants who completed the double-blind period, 322 entered the open-label extension study.” (opens the source at this quote in a new tab)

Baseline characteristics

No evidence found.

Efficacy results

No evidence found.

Health-related quality of life and patient-reported outcomes

Quality of Life in Epilepsy Inventory as a prespecified outcome measure

“Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time.” (opens the source at this quote in a new tab)

Safety results

No evidence found.

Study limitations

Summary: status of the X-TOLE4 evidence

X-TOLE4 is an open-label extension with no control group and no blinding, enrolling by invitation from the completers of X-TOLE2, X-TOLE3, and X-ACKT. Estimated primary completion is April 2033, and no efficacy, safety, disposition, or baseline data have been reported. Because participants from three antecedent trials with two different seizure types are pooled, outcomes reported from this study will not be specific to focal onset seizures unless reported separately by antecedent trial.