Clinical Trials Register

Summary
EudraCT Number:	2020-006057-21
Sponsor's Protocol Code Number:	CABL001A2302
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-12-09
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2020-006057-21

A.3

Full title of the trial

A phase 3b, multi-center, open-label, treatment optimization study of oral asciminib in patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP) previously treated with 2 or more tyrosine kinase inhibitors

Wieloośrodkowe badanie fazy IIIb prowadzone z zastosowaniem metody otwartej próby, mające na celu optymalizację doustnego leczenia ascyminibem u chorych na przewlekłą białaczkę szpikową w fazie przewlekłej (CML-CP), którzy byli w przeszłości leczeni co najmniej 2 inhibitorami kinazy tyrozynowej.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Asciminib treatment optimization in ≥ 3rd line CML-CP

A.4.1

Sponsor's protocol code number

CABL001A2302

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04948333

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma Services AG
B.5.2	Functional name of contact point	Punkt inform acyjny badania klinicz
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus / Lichtstrasse 35
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41 61 3241 111
B.5.5	Fax number	+41 61 3248 001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/20/2261
D.3 Description of the IMP
D.3.1	Product name	Asciminib
D.3.2	Product code	ABL001
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ASCIMINIB
D.3.9.2	Current sponsor code	ABL001
D.3.9.4	EV Substance Code	SUB188597
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/20/2261
D.3 Description of the IMP
D.3.1	Product name	Asciminib
D.3.2	Product code	ABL001
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ASCIMINIB
D.3.9.2	Current sponsor code	ABL001
D.3.9.4	EV Substance Code	SUB188597
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Myelogenous Leukemia in chronic phase (CML-CP)

E.1.1.1

Medical condition in easily understood language

CML is a bone marrow cancer caused by a gene mutation which causes over growth of white blood cells.

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	10009012
E.1.2	Term	Chronic myelogenous 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 the study is to estimate the molecular response
rate (MMR) of all the patients at week 48 with CML-CP following two or
more prior TKI treatments and with no evidence of MMR at baseline.

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability of asciminib in patients with CML-CP following two or more prior TKI treatments.
To assess the rate of MMR in patients without MMR at baseline and at alternative time points at weeks 12, 24, 36, 72, 96 and 144
To assess the rate of MMR at week 48 for patients with MMR at baseline
To assess the time to MMR
To assess the rate of early responses of BCR-ABL1 ≤10% and ≤1% at weeks 12, 24, 36 and 48
To assess the rate of deep molecular responses (MR4 and MR4.5) at weeks 12, 24, 36, 48, 72, 96 and 144
To assess cytogenetic response (% Ph+ metaphases) at weeks 48 and EOT.
To characterize the impact of additional cytogenetic abnormalities on efficacy
To assess cumulative molecular responses by all-time points
To assess duration of MMR
To assess sustained deep molecular responses as prerequisite for Treatment Free Remission (TFR)
To assess rate of progressions (PFS)
(Please refer to the protocol Table 2-1 for the full list)

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

'Single cell signaling and immune profiling sub-study to CABL001A2302'
Anticipated start date: Oct 2021
Objectives: Identify features of single cell immune and signaling profiles early after initiating asciminib treatment that predict: BCR-ABL1 (IS) level at 48 weeks (MMR or not), the decrease of BCR-ABL (IS) level during the first 6 months, AEs and patient reported outcomes

E.3

Principal inclusion criteria

Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
Treatment with a minimum of 2 or more prior TKIs (i.e. imatinib, nilotinib, dasatinib, bosutinib, radotinib or ponatinib)
Warning or failure (adapted from the 2020 ELN Recommendations) or intolerance to the most recent TKI therapy at the time of screening
Adequate end organ function (as per central laboratory tests)
Other protocol defined inclusion criteria may apply.

E.4

Principal exclusion criteria

Known presence of the BCR-ABL1 T315I mutation at any time prior to study entry
Known history of AP/BC
Previous treatment with a hematopoietic stem-cell transplantation
Patient planning to undergo allogeneic hematopoietic stem cell transplantation
Uncontrolled cardiac repolarization abnormality
Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
History of ongoing active acute or chronic liver disease
Other protocol defined exclusion criteria may apply

E.5 End points

E.5.1

Primary end point(s)

Major Molecular Response (MMR) rate at week 48.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 48

E.5.2

Secondary end point(s)

MMR rate at weeks 12, 24, 36, 72, 96 and 144.
MMR rate at week 48 for patients with MMR at baseline.
Time from the date of randomization to the date of first documented MMR
Rate of BCR-ABL1 ≤ 10% and ≤1% at weeks 12, 24, 36 and 48
Rate of MR4 and MR4.5 at weeks 12, 24, 36, 48, 72, 96 and 144.
Rate of complete cytogenetic response (CCyR) at weeks 48 and EOT.
Additional chromosomal abnormalities and occurrence of high-risk additional chromosomal abnormalities (ACAs)
Rate of BCR-ABL1 ≤ 10%, BCR-ABL1 ≤1%, MMR, MR4 and MR4.5 by all-time points.
Duration of MMR.
Duration of MR4 without loss of MMR.
Time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause.
Time from randomization to death.
Time from randomization to treatment failure define as BCR-ABL1 > 1%.
Change in symptom burden and interference from baseline over time according to the MDASI-CML PRO instrument.

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144/EOT.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability, cytogenetics

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Different regimen

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Argentina

Brazil

Canada

Korea, Republic of

Malaysia

Oman

Singapore

Viet Nam

Austria

France

Poland

Spain

Germany

Greece

Italy

Russian Federation

United Kingdom

E.8.7

Trial has a data monitoring committee

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

LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

124

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

186

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Please refer to the clinical protocol Section 6.1.4

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-01-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-12-15

P. End of Trial
P.	End of Trial Status	Ongoing

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