E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065336 |
E.1.2 | Term | Partial epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy, safety, and tolerability of VX-765 to treat seizures in subjects with treatment resistant partial epilepsy
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetics (PK) of VX-765, VRT 043198 (active metabolite of VX-765), and concomitant antiepileptic drug (AED) levels in subjects with treatment resistant partial epilepsy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males or females aged 18 to 64 (inclusive) years with a BMI between 18 and 35 (kg/m2)
• Subjects must agree to use acceptable contraceptive methods as described in Section 12.7.5. of the study protocol
• Subjects who have completed the assigned study treatment in Part A
may enter Part B if eligible per protocol
• Must have a diagnosis and hx of treatment-resistant partial-onset epilepsy (as defined in protocol) and are taking 1 to 4 stable doses of concomitant AEDs at the time of Screening Period
• Subjects must have had at least 1 EEG consistent with partial epilepsy
• Must have had at least 6 partial-onset seizures and a seizure free period of no more than 3 weeks during Baseline
• Subjects with stable medical conditions as determiend by Principal investigator
• Must understand and comply with the protocol requirements and be willing to provide written informed consent to participate |
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E.4 | Principal exclusion criteria |
• Subjects who are pregnant or lactating or do not agree to use medically approved methods of contraception as outlined in the protocol – for the duration od the study and for 90 days after last dose of study drug
• Subjects who are male and have a female partner who is pregnant, nursing, or is planning to become pregnant during the study period, or within 90 days of the last dose of study drug
• Subjects with a history of nonepileptic, transient alterations in consciousness (e.g., metabolic, structural, and post traumatic or pseudo seizures)
• Those who have a history of status epilepticus in the past 12 months before the Screening Visit
• Subjects whose seizure frequency cannot be quantified
• Subjects who have a significant medical illness including kidney, liver, pulmonary, or gastrointestinal disease; or unstable or poorly controlled conditions such as hypertension, diabetes, or angina pectoris, as judged by the investigator
• Subjects with clinically significant psychiatric illness or had an active suicidal plan/intent, thoughts, or attempt as defined in the study protocol
• Subjects with clinically significant laboratory abnormalities during the Screening Visit/Baseline Period, as judged by the investigator
• Subjects who have had serious adverse events (SAEs) thought to be
related to study drug that led to discontinuation during Part A may not
participate in part B
• Subjects with active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
• Subjects with positive drug screen at screening or during the Baseline Period (excluding any allowed prescribed medications) and/or a history of alcoholism or drug addiction within past 2 years
• Subjects on felbamate with fewer than 18 month of continuous felbamate exposure at the time of the Screening Visit or with significant adverse reactions to felbamate
• Subjects treated with vigabatrin fewer than 2 years prior to the Screening Visit or who have a prior history of treatment with vigabatrin without a documented stable examination by an ophthalmologist or neuroophthalmologist of the visual field within the 2 years prior to the Screening Visit
• Subjects using prohibited medications (Section 10.3 and Table 10 1) or treated with any systemic immunosuppressant as defined in the protocol
• Subjects who experienced a symptomatic viral, fungal, or bacterial infection requiring systemic treatment within 7 days prior to the first dose of study drug
• Subjects with a current or prior history of illness precluding them from immunomodulatory therapy
• Subjects who have donated any blood or have had a significant loss of blood (500 mL) as defined in the protocol
• Subjects who participated in any other clinical studies involving an investigational product or device and have received the last dose of the study drug associated with that clinical study within 30 days or 5 half lives (whichever is longer) of the Screening Visit
• Subjects who have participated in earlier VX-765 clinical studies and received at least one dose of study drug
• Subjects who have no completed the full 13-week Treatment Period in
part A may not participate in Part B
• Any subject judged by the investigator or sponsor (or designee) to be inappropriate for the study
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percent reduction in weekly seizure frequency during the Part A Late Treatment Period compared to the Part A Baseline Period
• Percent of subjects with 50% or greater reduction in weekly seizure frequency (responder rate) during the Part A Late Treatment Period compared to the Part A Baseline Period
• Safety and tolerability as assessed by vital signs, standard 12 lead electrocardiograms (ECGs), laboratory assessments (serum chemistry, hematology, and urinalysis), and adverse events
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Multiple timepoints up to Study Week 37 |
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E.5.2 | Secondary end point(s) |
• Percent of subjects who are seizure free during the Part A Late Treatment Period
• Percent reduction in seizure frequency during the entire Treatment Period compared to the Part A Baseline Period
• Percent of subjects with 50% or greater reduction in seizure frequency (responder rate) during the entire Part A Treatment Period compared to the Part A Baseline Period
• Percent of subjects who are seizure-free during the entire Part A Treatment Period
• Maximum number of consecutive days that subjects do not have seizures at any time during the Part A Late Treatment Period
• Maximum number of consecutive days that subjects do not have seizures at any time during the entire Part A Treatment Period
• PK of VX 765, VRT 043198, and concomitant AED levels in blood
• Percent reduction in weekly seizure frequency compared to the Part A Baseline Period
• Percent of subjects with 50% or greater reduction in weekly seizure frequency (50% responder-rate) during the entire Part B Treatment Period compared to the Part A Baseline Period
• Percent of subjects with 75% or greater reduction in weekly seizure frequency (75% responder-rate) during the entire Part B Treatment Period compared to the Part A Baseline Period
• Percent of subjects who are seizure-free during the entire Part B Treatment Period
• Maximum number of consecutive days that subjects do not have seizures at any time during the entire Part B Treatment Period
• Percent increase in weekly seizure-free days compared to the Part A Baseline Period |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Multiple timepoints up to Study Week 37 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 74 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Czech Republic |
France |
Germany |
Hungary |
Poland |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |