Clinical Trials Register

Summary
EudraCT Number:	2011-003715-28
Sponsor's Protocol Code Number:	HALO-109-201
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-04-13
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2011-003715-28

A.3

Full title of the trial

A Phase 1b/2 Multicenter, International, Randomized, Double Blind, Placebo-Controlled, Study of Gemcitabine Combined with PEGPH20 (PEGylated Recombinant Human Hyaluronidase) Compared to Gemcitabine Combined with Placebo in Patients with Stage IV Previously Untreated Pancreatic Cancer

Medzinárodné, multicentrické, randomizované, dvojito zaslepené, placebom kontrolované klinické skúšanie fázy 1b/2 porovnávajúce liečbu gemcitabínom v kombinácii s PEGPH20 (pegylovaná rekombinantná ľudská hyaluronidáza) a liečbu gemcitabínom v kombinácii s placebom u pacientov so štvrtým štádiom
predtým neliečeného karcinómu pankreasu.

A.4.1

Sponsor's protocol code number

HALO-109-201

A.5.4

Other Identifiers

Name:

IND

Number:

102770

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	Halozyme, 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	Halozyme, 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	Halozyme, Inc.
B.5.2	Functional name of contact point	Sam Dychter
B.5.3	Address:
B.5.3.1	Street Address	11388 Sorrento Valley Road
B.5.3.2	Town/ city	San Diego
B.5.3.3	Post code	CA 92121
B.5.3.4	Country	United States
B.5.4	Telephone number	+1858794 8889
B.5.5	Fax number	+1858704 8315
B.5.6	E-mail	sdychter@halozyme.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PEGylated Recombinant Human Hyaluronidase
D.3.2	Product code	PEGPH20
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	PEGPH20
D.3.9.3	Other descriptive name	PEGylated recombinant human hyaluronidase; H201; rHuPH20
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	PEGPH20 is a multi-site PEGylated enzyme generated by conjugating N-hydroxysuccinimidyl ester of methoxypoly(ethylene glycol)-butanoic acid (MSBA-30K or PEG) and rHuPH20.
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Gemcitabine Sun 1g powder for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Sun Pharmaceutical Industries Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GEMCITABINE HYDROCHLORIDE
D.3.9.1	CAS number	122111-03-9
D.3.9.4	EV Substance Code	SUB02324MIG
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	1000
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic Pancreatic Cancer

E.1.1.1

Medical condition in easily understood language

Metastatic Pancreatic Cancer

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10033605
E.1.2	Term	Pancreatic cancer metastatic
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase 1b
•To assess the safety and tolerability, and determine a safe dose of PEGPH20 to use in combination with the approved dose of gemcitabine
Phase 2 (in EU sites)
• To compare Overall Survival (OS) in gemcitabine plus PEGPH20 versus gemcitabine plus placebo treatment groups from the time of randomization.

E.2.2

Secondary objectives of the trial

•To compare the percent of patients in the gemcitabine plus PEGPH20 vs. gemcitabine plus placebo treatment groups that demonstrate a decrease in CA19-9 of ≥ 75% , ≥ 50% and ≥ 25%
• To assess the treatment effect by: ORR,DOR and PFS in all patients
• Monitor changes in pain assessment score in all patients
• To access tumor burden by RECIST 1.1 and CHOI criteria
• To assess OS and PFS at 3, 6, 9, and 12 months from the time of randomization
• To characterize PEGPH20 plasma PK
• To explore pharmacodynamic endpoints such as HA catabolites in serum and urine. Archived biopsies and optional pre- and post-dose tumor biopsiesfor staining of HA, tumor DCE-MRI and FDG-PET will also explore these endpoints
• To determine whether: 1) intensity of tumor-associated HA staining, 2) DCE-MRI perfusion, and/or 3) FDG-PET perfusion, anatomic data and metabolic activity, are associated with a decrease in CA19-9 levels, or other criteria.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients with histologically confirmed Stage IV adenocarcinoma of the pancreas previously untreated for metastatic disease
• One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria
• Baseline CA19-9 of ≥ 100 U/mL in the absence of biliary obstruction or other physiological process unrelated to the tumor that may cause an elevation in CA19-9 levels
• Karnofsky performance status ≥ 70%
• Life expectancy of at least 3 months
• Age ≥ 18 years
• Signed, written IRB/EC-approved informed consent
• A negative serum pregnancy test, if female
• Acceptable liver function:
− Bilirubin ≤ 1.5 times upper limit of normal
− AST (SGOT) and ALT (SGPT) ≤ 2.5 times upper limit of normal, (if liver metastases are present, then ≤ 5 times upper limit of normal is allowed)
− Alkaline phosphatase ≤ 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 times upper limit of normal is allowed)
• Acceptable renal function:
− Serum creatinine within normal limits, OR calculated creatinine clearance ≥ 40 mL/min/1.73 m2 for patients with creatinine levels above normal
• Acceptable hematologic status:
− ANC ≥ 1,500 cells/mm3
− Platelet count ≥ 150,000 plt/mm3
− Hemoglobin ≥ 9 g/dL
• Acceptable coagulation status:
− PT/INR within normal limits or INR 2.0-3.0 if on warfarin
− PTT within normal limits, or within 1.2xULN if on warfarin
• Baseline ejection fraction done by MUGA Scan ≥ 50%
• For men and women of child-producing potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study

E.4

Principal exclusion criteria

• Known brain metastasis
• New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 12 months, or cardiac arrhythmia requiring medical therapy
• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy
• Known infection with HIV, hepatitis B, or hepatitis C
• Known allergy to hyaluronidase
• Women currently pregnant or breast feeding
• Heparin therapy administered IV
• Intolerant to Dexamethasone

E.5 End points

E.5.1

Primary end point(s)

•For the Phase 1b portion of the study, the primary objectives are to assess safety, tolerability, and to determine a safe dose of PEGPH20 to use in combination with the approved dose of gemcitabine for Phase 2.
• For Phase 2, OS is the primary endpoint. OS is defined as the interval from the date of randomization to the date of death due to any cause. OS will be reported using a Kaplan-Meier estimate (median and 95% confidence interval) for each treatment group for all patients in the ITT population. The log-rank test will be used to test for treatment group differences.

E.5.1.1

Timepoint(s) of evaluation of this end point

As per Study schedule of events (included in the Study protocol)

E.5.2

Secondary end point(s)

• The CA19-9 response rate (also defined as the number of patients achieving a ≥25%, ≥50% or ≥75% decline in CA19-9 from baseline divided by the total number of patients in the ITT Population). The proportion of patients that achieved a ≥25%, ≥50% or ≥75% decline in CA19-9 from baseline along with the 95% confidence interval will be reported for each treatment group. The Fishers exact test will be used to test for treatment group differences.
• ORR as defined by RECIST 1.1 criteria will be evaluated. The objective response rate (complete response [CR] + partial response [PR] + stable disease [SD]), as well as the rates for the individual categories of response (i.e., CR, PR, SD, and PD), will be estimated by the percentage of ITT patients achieving these criteria. The proportion of patients that responded along with the 95% confidence interval will be reported for each treatment group. The Fishers exact test will be used to test for treatment group differences in the objective response rate. Response will also be assessed using CHOI criteria.
• DOR is defined as the interval from the demonstration of a CR, PR or SD to the earliest documented evidence of recurrent or progressive disease, or the date of death due to any cause, whichever occurs first. DOR will be reported using a Kaplan-Meier estimate (median and 95% confidence interval) for each treatment group only on patients achieving a response (CR, PR, or SD). The log-rank test will be used to test for treatment group differences.
• PFS is defined as the interval from the date of randomization to the earliest date of documented evidence of recurrent or progressive disease, or the date of death due to any cause, whichever occurs first. PFS will be reported using a Kaplan-Meier estimate (median and 95% confidence interval) for each treatment group for all patients in the ITT population. The log-rank test will be used to test for treatment group differences.
• Change in pain assessment score will be displayed by use of descriptive statistics overtime (monthly) by treatment group.
• OS and PFS rates at Months 3, 6, 9, 12 will be displayed using descriptive statistics (number and percent) by treatment group.

E.5.2.1

Timepoint(s) of evaluation of this end point

As per protocol.

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

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase 1b (not in EU sites)

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

Yes

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

Phase 1b - open label, Phase 2-double blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

PEGPH20+gemcitabine vs. Placebo+gemcitabine

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

Czech Republic

Hungary

Romania

Russian Federation

Slovakia

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

LSLV

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.1.3

Elderly (>=65 years)

Yes

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.4.2.2

In the whole clinical trial

147

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)

As per study protocol

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-04-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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