Study to determine the dose and safety of asciminib in pediatric patients with chronic myeloid leukemia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Sep 2022 → ongoing

Decision date (initial)

2024-06-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-508129-28-00

EudraCT number

2021-001286-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacogenomic, Pharmacokinetic, Dose response, Safety, Others, Pharmacogenetic

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).

Secondary objectives 4

1. To assess the safety and tolerability of asciminib.
2. To assess pharmacodynamic markers of asciminib's anti-leukemic activity.
3. To assess acceptability and palatability of the pediatric formulation.
4. To assess long-term safety of asciminib.

Conditions and MedDRA coding

Pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP), previously treated with one or more tyrosine kinase inhibitors

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002347-PIP01-18

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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.
2. Participants with Ph+ CML-CP 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 locally 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
3. Prior treatment with a minimum of one TKI.
4. Failure or intolerance to the most recent TKI therapy at the time of screening.
5. 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.

Exclusion criteria 5

1. Known presence of the T315I mutation prior to study entry or of a BCR: ABL mutation with known resistance to study treatment any time prior to study entry
2. Known second chronic phase of CML after previous progression to AP/BC.
3. Previous treatment with a hematopoietic stem-cell transplantation.
4. Patient planning to undergo allogeneic hematopoietic stem cell transplantation.
5. Cardiac or cardiac repolarization abnormality.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary PK parameters of asciminib: AUClast, AUCtau
2. Secondary PK parameters of asciminib: Cmax, Tmax, Ctrough.

Secondary endpoints 4

1. Number, seriousness, severity, and causality assessments of treatment-emergent adverse events and other safety data as considered appropriate.
2. Activity: Hematologic and molecular responses.
3. Questionnaire on acceptability and palatability after first dose, 4 and 52 weeks.
4. Number, seriousness, severity, and causality assessments of treatment-emergent adverse events and other safety data as considered appropriate including growth and sexual maturation assessments.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 17

Locations

7 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications