Clinical Trials Register

Summary
EudraCT Number:	2013-004105-11
Sponsor's Protocol Code Number:	GS-US-354-0101
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-01-23
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

2013-004105-11

A.3

Full title of the trial

A Phase 2, Open-label, Randomized Study to Evaluate Safety and Efficacy of Momelotinib in Subjects with 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 Polycythemia Vera & Essential Thrombocythemia.

A.4.1

Sponsor's protocol code number

GS-US-354-0101

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01998828

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	International Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Flowers Building, 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.5.4	Telephone number	+441223897356
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 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	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 the study is to determine the efficacy of MMB in subjects with PV or ET

E.2.2

Secondary objectives of the trial

The secondary objective of the study is to determine the safety of MMB in subjects with PV or ET

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥ 18 years old
2.Diagnosis of either PV or ET as defined by the 2008 WHO Diagnostic Criteria
3.Requires treatment for PV or ET, in the opinion of the study investigator
4.Intolerant of, resistant to, or refuses current or available treatment for PV or ET
5.Direct bilirubin ≤ 2.0 x upper limit of normal (ULN)
6.AST (SGOT) and ALT (SGPT) ≤ 3X ULN
7.Calculated creatinine clearance (CrCl) of ≥ 45 mL/min
8.Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
9.Life expectancy > 24 weeks
10.Negative serum pregnancy test for female subjects (unless surgically sterile or greater than two years postmenopausal)
11.Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
12.Females who are nursing must agree to discontinue nursing before the first dose of IP
13.Able to comprehend and willing to sign informed consent form (ICF)

E.4

Principal exclusion criteria

1.Prior splenectomy
2.Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection (subjects receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the study), active or chronic bleeding event within 4 weeks prior to first dose of IP, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician
3.History of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, adequately treated Stage 1 or 2 cancer currently in complete remission (CR), or any other cancer that has been in CR for ≥ 5 years.
4.Major surgery within 28 days of first dose of IP
5.Known positive status for human immunodeficiency virus (HIV)
6.Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
7.Myeloproliferative neoplasm-directed therapy, other than aspirin, hydroxyurea, anagrelide, and/or phlebotomy, within 21 days prior to the first dose of IP
8.Anagrelide within 7 days prior to the first dose of IP
9.Unresolved non-hematologic toxicities from prior therapies that are > CTCAE Grade 1
10.Presence of peripheral neuropathy ≥ Grade 2
11.Incomplete recovery from any surgery performed within 4 weeks prior to the first dose of IP
12.Unwilling or unable to take oral medication
13.Prior use of a JAK1 or JAK2 inhibitor
14.Use of strong CYP3A4 inducers within 1 week prior to the first dose of IP
15.Known hypersensitivity to the study investigational medicinal products, the metabolites, or formulation excipients
16. QTc interval > 450msec, unless attributed to bundle branch block

E.5 End points

E.5.1

Primary end point(s)

the primary endpoint is defined by the ORR.

In the PV Cohort, the ORR is defined as the proportion of subjects with hematocrit < 45% in the absence of phlebotomy, WBC < 10 x 10^9/L, platelet count ≤ 400 x 10^9/L and resolution of palpable splenomegaly. All these criteria have to last at least 4 weeks.

In the ET Cohort, the ORR is defined as the proportion of subjects with Platelet count ≤ 400 x 10^9/L, WBC < 10 x 10^9/L and resolution of palpable splenomegaly. All these criteria have to last at least 4 weeks.

In order to be counted as a responder for PV and ET, a subject must meet all of the above criteria at some point during the treatment period. However, 4 criteria for PV or the 3 criteria for ET do not have to be met for the same 4 weeks.

E.5.1.1

Timepoint(s) of evaluation of this end point

Monitoring will be conducted intensively for the first 24 weeks (biweekly the first 8 weeks, and after every 4 weeks through week 24 / Early
Study Drug Discontinuation) of the study.

E.5.2

Secondary end point(s)

1. Confirmed ORR – defined as the proportion of subjects who meet all the criteria listed for the primary endpoints of PV or ET, sustained for at least 12 weeks. The 4 criteria for PV or the 3 criteria for ET do not have to be met for the same 12 weeks.
2. Proportion of subjects with hematocrit < 45% in the absence of phlebotomy that lasts at least 4 weeks
3. Proportion of subjects with WBC < 10 x 10^9/L that lasts at least 4 weeks
4. Proportion of subjects with platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks
5. Proportion of subjects with resolution of palpable splenomegaly that lasts at least 4 weeks
6. Proportion of subjects with ≥ 10 point decrease in modified MPNSAF TSS compared to baseline that lasts at least 12 weeks

E.5.2.1

Timepoint(s) of evaluation of this end point

Monitoring will be conducted intensively for the first 24 weeks (biweekly the first 8 weeks, and after every 4 weeks through week 24 / Early
Study Drug Discontinuation) 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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

Yes

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

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

Yes

E.8.2.3.1

Comparator description

2 strengths of Momelotinib are compared.

E.8.2.4

Number of treatment arms in the trial

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:

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

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, subjects who respond to treatment, or at investigator’s discretion, have the option of maintenance therapy with MMB on Study GS-US-352-1154 at the MMB dose they tolerated and/or derived clinical benefit from during the 24-week treatment period.

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

2014-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-05-01

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