E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
BRAF-Altered, Recurrent or Progressive Low-Grade Glioma in pediatric patients
|
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006153 |
E.1.2 | Term | Brain tumor |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of DAY101 in pediatric patients aged 6 months to 25 years of age with a relapsed or progressive low-grade glioma (LGG) harboring a known activating BRAF alteration. |
|
E.2.2 | Secondary objectives of the trial |
- To assess safety and tolerability of DAY101 - To determine the relationship between pharmacokinetics (PK) and drug effects, including efficacy and safety
For the complete list of secondary objectives please refer to the protocol Section 2 "Study Objectives". |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 6 months to 25 years with a relapsed or progressive LGG with a documented known activating BRAF alteration. - Confirmation of histopathologic diagnosis of LGG from either original diagnosis or relapse - Must have received at least 1 line of systemic therapy prior and have documented evidence of radiographic progression - Must have at least 1 measurable lesion - Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.
For the complete list of the inclusion criteria, please refer to the protocol. |
|
E.4 | Principal exclusion criteria |
- Patient has symptoms of clinical progression without radiographically recurrent or radiographically progressive disease. - History of any major disease, other than the diagnosis of LGG, that might interfere with safe protocol participation - Major surgery within 14 days (2 weeks) prior to C1D1 - Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to C1D1 - Current enrollment in any other investigational treatment study. Participation in a concurrent observational or bio-sampling study is allowed.
For the complete list of the exclusion criteria, please refer to the protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of Cycle 3, end of Cycle 6, and ever 3 cycles thereafter. Please see Appendix A of the protocol. |
|
E.5.2 | Secondary end point(s) |
-Type, frequency, and severity of AEs and laboratory abnormalities - Pharmacokinetic profile of DAY101 (e.g., area under the concentration-time curve [AUC], Cmin, etc.) - time following initiation of DAY101 to progression or death in patients treated with DAY101 - length of response in patients with best overall confirmed response of CR or PR - time to first response following initiation of DAY101 in patients with best overall confirmed response of CR or PR
Please see Table 6 in protocol for further information. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
AEs: From the start of treatment with DAY101 until 30 days after the last dose. PK profile (blood sampling): C1D1, C1D15, C2D1, C41, Every 3rd cycle, At the time of toxicity, and/or at time of surgery, if clinically indicated. Change from QT interval, baseline PR interval, baseline QRS interval, baseline heart rate,
Please see Appendix A of the protocol for further details. |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
Australia |
Canada |
Israel |
Korea, Republic of |
Singapore |
United States |
Denmark |
Germany |
Netherlands |
Switzerland |
United Kingdom |
|
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |