E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP), previously treated with one or more tyrosine kinase inhibitors |
|
E.1.1.1 | Medical condition in easily understood language |
Cancer of the bone marrow |
|
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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054352 |
E.1.2 | Term | Chronic phase chronic myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060498 |
E.1.2 | Term | Juvenile chronic myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 24.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10082178 |
E.1.2 | Term | Philadelphia positive chronic myeloid leukemia |
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 |
The primary objective of this study is to characterize the pharmacokinetic (PK) profile of asciminib in pediatric patients, with the goal of identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted). |
|
E.2.2 | Secondary objectives of the trial |
•To assess the safety and tolerability of asciminib. •To assess pharmacodynamic markers of asciminib’s anti-leukemic activity. •To assess acceptability and palatability of the pediatric formulation. •To assess long-term safety of asciminib. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female participants: a. Pediatric formulation group: ≥1 and less than 18 years of age at study entry. b. Adult formulation group: ≥14 and less than 18 years of age and body weight of ≥ 40 kg at study entry. • Participants must meet all of the following laboratory values at the screening visit. In the case where bone marrow blast and promyelocyte counts are available, these will be accepted if done within 56 days prior to the screening visit, to avoid unnecessary repetition of this test. a. 15% blasts in peripheral blood and bone marrow b. < 30% combined blasts plus promyelocytes in peripheral blood and bone marrow c. < 20% basophils in the peripheral blood d. Neutrophils ≥ 1.5 x 10^9/L (or white blood cell (WBC) ≥ 3 x 10^9/L if neutrophils are not available) and platelet count ≥ 100 x 10^9/L e. No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly • Prior treatment with a minimum of one TKI. • Failure or intolerance to the most recent TKI therapy at the time of screening. • Evidence of typical BCR-ABL fusion gene (BCR-ABL1) transcript [e14a2 and/or e13a2] at the time of screening which are amenable to standardized real time quantitative polymerase chain reaction (RQ-PCR) quantification. |
|
E.4 | Principal exclusion criteria |
• Known presence of the T315I mutation prior to study entry. • Known second chronic phase of CML after previous progression to AP/BC. • Previous treatment with a hematopoietic stem-cell transplantation. • Patient planning to undergo allogeneic hematopoietic stem cell transplantation. • Cardiac or cardiac repolarization abnormality. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Primary PK parameters of asciminib: AUClast, AUCtau • Secondary PK parameters of asciminib: Cmax, Tmax, Ctrough.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary analysis after last patient has completed week 52 visit |
|
E.5.2 | Secondary end point(s) |
• Number, seriousness, severity, and causality assessments of treatment-emergent adverse events and other safety data as considered appropriate. • Activity: Hematologic and molecular responses. • Questionnaire on acceptability and palatability after first dose, 4 and 52 weeks. • Number, seriousness, severity, and causality assessments of treatment-emergent adverse events and other safety data as considered appropriate including growth and sexual maturation assessments. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Final analysis after last patient completes week 260 visit |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, acceptability, and palatability |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Pharmacokinetic/Pharmacodynamic |
|
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 | 14 |
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 |
China |
Japan |
Korea, Republic of |
Russian Federation |
Thailand |
Turkey |
United States |
France |
Germany |
Greece |
Hungary |
Italy |
Netherlands |
Poland |
|
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
|
End of trial is when the LVLS after 5 years of treatment |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |