Clinical Trials Register

Summary
EudraCT Number:	2013-004476-36
Sponsor's Protocol Code Number:	GS-US-352-1154
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-02
Trial results	View 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

Germany - BfArM

A.2

EudraCT number

2013-004476-36

A.3

Full title of the trial

Open-label Study to Assess the Long-term Safety and Efficacy of Momelotinib in Subjects with Primary Myelofibrosis, Post polycythemia Vera Myelofibrosis, Post essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia

A.3.1

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

A clinical trial with Momelotinib in subjects with Primary Myelofibrosis, Post polycythemia Vera Myelofibrosis, Post essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia

A.4.1

Sponsor's protocol code number

GS-US-352-1154

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02124746

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	Gilead Sciences, Inc.
B.1.3.4	Country	United States
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	Gilead Sciences, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gilead Sciences International Ltd.
B.5.2	Functional name of contact point	Clinical Trials Mailbox
B.5.3	Address:
B.5.3.1	Street Address	Granta Park
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB21 6GT
B.5.3.4	Country	United Kingdom
B.5.5	Fax number	+441223897284
B.5.6	E-mail	clinical.trials@gilead.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	EMA/OD/152/10
D.3 Description of the IMP
D.3.1	Product name	momelotinib 100mg
D.3.2	Product code	GS-0387
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	momelotinib dihydrochloride monohydrate
D.3.9.2	Current sponsor code	GS-0387-01 monohydrate
D.3.9.3	Other descriptive name	MOMELOTINIB
D.3.9.4	EV Substance Code	SUB126831
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	100
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	EMA/OD/152/10
D.3 Description of the IMP
D.3.1	Product name	momelotinib 150mg
D.3.2	Product code	GS-0387
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	momelotinib dihydrochloride monohydrate
D.3.9.2	Current sponsor code	GS-0387-01 monohydrate
D.3.9.3	Other descriptive name	MOMELOTINIB
D.3.9.4	EV Substance Code	SUB126831
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	150
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: 3
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	EMA/OD/152/10
D.3 Description of the IMP
D.3.1	Product name	momelotinib 200mg
D.3.2	Product code	GS-0387
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	momelotinib dihydrochloride monohydrate
D.3.9.2	Current sponsor code	GS-0387-01 monohydrate
D.3.9.3	Other descriptive name	MOMELOTINIB
D.3.9.4	EV Substance Code	SUB126831
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	200
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

subjects with either primary myelofibrosis (PMF) or post polycythemia vera myelofibrosis or post essential thrombocythemia myelofibrosis (post-PV / ET MF) or polycythemia vera (PV) or essential thrombocythemia (ET)

E.1.1.1

Medical condition in easily understood language

Blood disorder that means the body produces too many mature blood cells too quickly

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10036057
E.1.2	Term	Polycythaemia vera
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10028537
E.1.2	Term	Myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10015493
E.1.2	Term	Essential thrombocythaemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 determine the long-term safety and tolerability of MMB in 3 cohorts of subjects:
•Cohort 1: Subjects who are currently receiving MMB capsules in the CCL09101E study for PMF and post-PV/ET MF without documented progressive disease
•Cohort 2: Subjects who are currently receiving MMB capsules in the YM387-II-02 study for PMF and post-PV/ET MF without documented progressive disease
•Cohort 3: Subjects who are currently receiving MMB tablets in the GS-US-354-0101 study for PV or ET, who complete 24 weeks of treatment and whose disease has not progressed on study. Only the cohort 3 is relevant to EU subjects.

E.2.2

Secondary objectives of the trial

The secondary objective of this study is to determine the long-term efficacy of MMB in these 3 cohorts of subjects.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Currently enrolled in study CCL09101E, or YM387-II 02, or successfully completed 24 weeks of study GS US 354 0101
•Did not end treatment with MMB for any reason other than to enroll in this study
•Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at enrollment of this study
•Negative serum or urine pregnancy test is required for female subjects (unless surgically sterile or greater than two years post-menopausal)
•Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
•Ability and agreement to attend protocol-specified visits at the study site
•Any Grade 3 or 4 non-hematologic toxicity that the investigator considers related to previous MMB use must have resolved, reverted to Grade 1, or to baseline of the prior study prior to Day 1 of this study
•Able to comprehend and willing to sign the informed consent form

E.4

Principal exclusion criteria

•Known hypersensitivity to MMB, its metabolites, or formulation excipients
•Incomplete recovery from major surgery prior to Day 1 of this study
•Presence of peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events CTCAE Grade 3
•Known positive status for human immunodeficiency virus (HIV)
•Known chronic active or acute viral hepatitis A, B, or C infection

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is safety. Safety will be evaluated by the incidence and severity of adverse events and clinical laboratory abnormalities, as defined by CTCAE v4.03.

E.5.1.1

Timepoint(s) of evaluation of this end point

Monitoring will be conducted on a quarterly basis through month 48 / End of Treatment of the study. Additionally, serious adverse events will be reported as soon as they are raised.

E.5.2

Secondary end point(s)

Secondary endpoints are:
•Overall survival (OS): defined as the interval from the first dose of MMB on the previous study until death from any cause
•Progression-free survival (PFS): defined as the interval from the first dose of MMB on the previous study until the first documentation of definitive progressive disease or death due to any cause
•Leukemia free survival: defined as the interval from the first dose of MMB on the previous study until the first documented leukemic transformation or death from any cause
•Rate of RBC transfusion: defined as the average number of RBC units per subject month from the first dose of MMB on the previous study during the study period

Other secondary endpoints specific to Cohorts 1 and 2:
•Duration of splenic response: defined as the interval from the first onset of splenic response (in the previous study or this study) to the earliest date of loss of splenic response which persists for at least 4 weeks or death from any cause. Splenic response is defined as > 50% reduction in palpable splenomegaly of a spleen that is ≥ 10 cm below the LCM at baseline or a spleen that is palpable at > 5 cm below the LCM at baseline becomes not palpable.
•Duration of transfusion independence response: defined as the interval from the first onset date of transfusion independence (in the previous study or this study) to the earliest onset date of transfusion dependence or death from any cause, among those subjects who are transfusion dependent at baseline. Transfusion independence is defined as absence of RBC transfusions for ≥ 8 weeks.
•Duration of anemia response: defined as the interval from the first onset of anemia response (in the previous study or this study) to the earliest date of loss of anemia response which persists for at least 4 weeks or death from any cause. Anemia response is defined as ≥ 2g/dL increase in hemoglobin for baseline transfusion independent subjects with baseline hemoglobin level of < 10g/dL, or becoming transfusion independent for those who were transfusion dependent at baseline for ≥ 8 weeks.
Other endpoints specific to Cohort 3:
•Overall response rate (ORR) : Confirmed ORR is defined as the proportion of subjects with onset of response in the previous study with the 12 week confirmation reached during this study.

E.5.2.1

Timepoint(s) of evaluation of this end point

Monitoring will be conducted on a quarterly basis through month 48 / End of Treatment of the study.

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

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

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

Cohort

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

Australia

Canada

France

Germany

United States

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

LVLS

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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:

105

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

160

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)

After a patient has completed / terminated their study participation, long term care for the participant will remain the responsibility of their primary treating physician

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

2014-10-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-12-06

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