Clinical Trials Register

Summary
EudraCT Number:	2008-006140-20
Sponsor's Protocol Code Number:	005/05
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-04-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2008-006140-20

A.3

Full title of the trial

A Randomized Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Treatment
with OncoVEX GM-CSF Compared to Subcutaneously Administered GM-CSF in Melanoma Patients with Unresectable Stage IIIb, IIIc and IV Disease

A.4.1

Sponsor's protocol code number

005/05

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	BioVex 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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	OncoVEX GM-CSF
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intratumoral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	OncoVEX GM-CSF
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/ml plaque forming unit(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	3 x 10e7 to 3 x 10e8
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)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	OncoVEX GM-CSF
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intratumoral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	OncoVEX GM-CSF
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/ml plaque forming unit(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	3 x 10e5 to 3 x 10e6
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)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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	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	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	GM-CSF
D.3.2	Product code	NDC no 50419-050 (Bayer) or 58468-0181-2 (Genzyme)
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	sargramostim
D.3.9.1	CAS number	83869-56-1
D.3.9.2	Current sponsor code	GM-CSF
D.3.9.3	Other descriptive name	Leukine
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Information not present in EudraCT

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

Unresectable Stage IIIb, IIIc and IV Melanoma

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is achieving a statistically significant improvement in
durable response rate (DRR), defined as the rate of objective response (CR or PR) lasting continuously for 6 or more months, as compared to control therapy, and beginning at any point within 12 months of initiating therapy.

E.2.2

Secondary objectives of the trial

• To evaluate safety
• To evaluate overall survival in patients treated with OncoVEX GM-CSF as compared to control therapy.
• To analyze response onset in patients treated with OncoVEX GM-CSF or GM-CSF.
• To evaluate time to treatment failure in patients treated with OncoVEX GM-CSF or GM-CSF.
• To estimate duration of response in patients treated with OncoVEX GM-CSF or GM-CSF.
• To evaluate best response and disease burden in patients treated with OncoVEX GM-CSF or GM-CSF.
• To analyze response interval in the 2 treatment arms.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Males or females age ≥ 18 years.
2.Histologically confirmed diagnosis of malignant melanoma.
3.Stage IIIb, IIIc or stage IV disease that is not surgically resectable.
4.Measurable disease defined as:
•at least 1 melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the greatest diameter is ≥ 10 mm as measured by contrast-enhanced or spiral computed tomography (CT) scan for visceral or nodal/soft tissue disease (including lymph nodes) and/or;
•at least 1 ≥ 10 mm superficial cutaneous melanoma lesion as measured by calipers and/or;
•at least 1 ≥ 10 mm subcutaneous melanoma lesion and/or;
•multiple superficial melanoma lesions which in aggregate have a total diameter of ≥ 10 mm.
5.Injectable disease (i.e. suitable for direct injection or through the use of ultrasound guidance) defined as:
•at least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion ≥ 10 mm in longest diameter or;
•multiple injectable melanoma lesions which in aggregate have a longest diameter of ≥ 10 mm.
6.Serum LDH levels ≤ 1.5 x ULN.
7.ECOG Performance Status of 0 or 1.
8.Life expectancy >4 months from the date of randomization.
9.Provide written informed consent in accordance will all applicable regulations and follow the study procedures. Patients must be capable of understanding the investigational nature, potential risks and benefits of the study.
10.Adequate organ function determined within 4 weeks prior to randomization, defined further in the protocol

E.4

Principal exclusion criteria

1.Clinically active cerebral or any bone metastases. Patients with up to 3 (neurological performance status of 0) cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, gammaknife therapy, with no evidence of progression, and have not required steroids, for at least two (2) months prior to randomization.
2.Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For patients with ≤ 3 visceral metastases, no lesion >3 cm, and liver lesions must meet RECIST criteria for SD for at least 1 month prior to randomization.
3.Any underlying medical condition, which in the opinion of the investigator, would make administration of the study drugs hazardous or make it difficult to monitor adverse effects.
4.History of second cancer unless disease-free for >5 years. In the case of malignancies that are diagnosed at a stage where a definitive therapy results in near certain cure, a disease free interval of <5 years is permissible. The Medical Monitor must approve such patients.
5. Primary ocular or mucosal melanoma.
6. Evidence of immunosuppression for any reason:
•known HIV disease
•acute or chronic active hepatitis B or hepatitis C infection
•chronic oral or systemic steroid medication use at a dose of >10mg/day of prednisone or equivalent (steroids with low systemic absorption [e.g., triamcinolone hexacetonide] injected into a joint space is allowed)
•other signs or symptoms of clinical immune system suppression
7.Baseline prolongation of QT/QTc interval (QTc interval >470 msec).
8.Open herpetic skin lesions.
9.Pregnant or breast-feeding female. Confirmation that women of child-bearing potential are not pregnant. A negative serum or urine β-human chorionic gonadotropin (β-hCG) pregnancy test result must be obtained during the screening period.
10. Fertile males and females who are unwilling to employ adequate means of contraception (e.g., condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches, or intrauterine device) during study treatment and through 30 days after the last dose of study treatment.
11.Previous treatment with OncoVEXGM-CSF or treatment with GM-CSF for active disease (prior adjuvant therapy with GM-CSF is permitted).
12.Currently enrolled in another clinical research study or received an investigational agent for any reason within 4 weeks prior to randomization.
13.Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the rate of objective responses (CR + PR) maintained for at
least 6 months (DRR) initiating at any time within 12 months of commencing therapy.

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

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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

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

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)

Yes

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

Yes

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

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

Information not present in EudraCT

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

160

F.4.2.2

In the whole clinical trial

430

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)

Those patients randomized to OncoVEX GM-CSF that have not achieved a response, nor progressed, and treatment beyond 12 months is warranted will have the option of being transferred to an extended use OncoVEXGM-CSF treatment protocol where they will continue to receive OncoVEXGM-CSF and followed for efficacy and safety. GM-CSF may also be made available to a patient randomized to GM-CSF if further treatment beyond 12 months is warranted.

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

2009-06-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-05-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-08-08

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials