Clinical Trials Register

Summary
EudraCT Number:	2014-000095-26
Sponsor's Protocol Code Number:	MED-GX301-02
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-04-09
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-000095-26

A.3

Full title of the trial

A randomised, parallel-group, open-label Phase II trial of the immunological effects of three regimens of GX301 vaccination in castration-resistant prostate cancer patients who have achieved response to first-line chemotherapy.

A.3.1

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

A.4.1

Sponsor's protocol code number

MED-GX301-02

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	Laboratoires Leurquin Mediolanum S.A.S.
B.1.3.4	Country	France
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	Laboratoires Leurquin Mediolanum S.A.S.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mediolanum Farmaceutici S.p.A.
B.5.2	Functional name of contact point	Project Leader
B.5.3	Address:
B.5.3.1	Street Address	via S. G. Cottolengo, 15
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20143
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390289132263
B.5.6	E-mail	d.criscuolo@mediolanum-farma.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	MED-GX301-02
D.3.2	Product code	MED-GX301-02
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
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)	Yes
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Montanide ISA 51 VG
D.3.2	Product code	Montanide ISA 51 VG
D.3.4	Pharmaceutical form	Emulsion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
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	Yes
D.2.1.1.1	Trade name	Aldara 5% cream
D.2.1.1.2	Name of the Marketing Authorisation holder	Meda AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Cream
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
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

Castration-resistant prostate cancer (patients who have achieved response to first-line docetaxel chemotherapy).

E.1.1.1

Medical condition in easily understood language

Castration-resistant prostate cancer (patients who have achieved response to first-line docetaxel chemotherapy).

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	16.1
E.1.2	Level	PT
E.1.2	Classification code	10062904
E.1.2	Term	Hormone-refractory prostate cancer
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

To compare three different GX301 administration regimens in castration-resistant prostate cancer patients who have responded to first-line docetaxel, for the following co-primary outcomes:
• efficacy in inducing vaccine-specific immunological responses over a period of 6 months following randomisation;
• treatment safety and tolerability over the same period.

E.2.2

Secondary objectives of the trial

• To compare the three GX301 regimens for the following secondary outcomes:
- time-course of serum PSA;
- progression-free survival (censored at 18 months from randomisation);
- overall survival (censored at 24 months);
- treatment safety and tolerability beyond 6 months from randomisation.
• To investigate whether achievement of immunological response, irrespective of the assigned GX301 regimen, is related to progression-free and/or overall survival.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patient history
Eligible patients will have a documented history of the following:
 Histologically confirmed diagnosis of prostate cancer, with an available Gleason score.
 Diagnosis of progressive, castration-resistant prostate cancer (CRPC), leading to inception of first-line chemotherapy with a docetaxel-based regimen.
CRPC is defined as progression in PSA levels and/or in bone lesions or soft-tissue (visceral, nodal) lesions that has occurred during therapy with: front-line concurrent LHRH agonist and anti-androgen (maximal androgen blockade); or an anti-androgen added to front-line LHRH agonist following failure of the latter; or an LHRH-agonist replacing, or added to, front-line anti-androgen following failure of the latter.
Progression must have been observed: in all cases, in the presence of castrate serum testosterone levels (≤50 ng/dL or 1.7 nmol/L); in patients receiving anti-androgen therapy, following 6 or more weeks from discontinuation of the anti-androgen agent.
 Completion of chemotherapy with a cumulative delivered dose of 300 to 825 mg/m2 docetaxel.
Current patient status
 Age ≥18 years.
 Ability to understand study-related patient information and provision of written informed consent for participation in the study.
 Symptomatic or asymptomatic status (as for cancer-related symptoms).
 ECOG performance status of 0 or 1.
 Life expectancy of at least 6 months.
 An interval ≥4 weeks elapsed from the last docetaxel administration.
 Documented response to docetaxel chemotherapy. This is defined as post-chemotherapy PSA and imaging findings showing all of the following, as compared with the pre-chemotherapy documentation:
a) a PSA decrease ≥50% confirmed in two consecutive determinations obtained approximately 4 weeks apart;
b) absence of new bone lesions at radionuclide bone scan;
c) a status of soft-tissue (nodal, visceral) lesions meeting RECIST criteria for complete response or partial response.
 Current castrate testosterone level (≤50 ng/dL or 1.7 nmol/L) due to current GnRH agonist or antagonist therapy or past orchiectomy.
 Withdrawal of antiandrogen therapy, if any, for at least 4 weeks prior to randomization.
 Haematology and blood chemistry values (central laboratory) complying with the following criteria:
- Total WBC count  3.0x109/L (to ensure that of a sufficient number of lymphocytes are available for the immunological tests)
- Platelets  100x109/L
- Serum bilirubin 1.5 times the upper normal limit (UNL)
- Alkaline phosphatase  3.0 times the UNL
- AST and ALT  2.5 times the UNL
- Creatinine 1.5 mg/dL (133 μmol/L).
 Successful recovery from all acute toxicities from prior chemotherapy (except alopecia, grade 2 peripheral neuropathy and change in nails).
 Confirmation from the immunology laboratory that the blood sample provided for baseline immunological tests is technically adequate.

E.4

Principal exclusion criteria

 Known intolerance to Montanide or imiquimod. Montanide adjuvants are found as ingredients of experimental human vaccines. Imiquimod is the active ingredient of Aldara, a medicinal product for topical use.
 Known presence of brain metastatic disease or spinal cord compression.
 Radiotherapy within the past 4 weeks.
 Concomitant presence of other primary malignancy except for non-melanomatous skin cancer, unless it was diagnosed and successfully treated ≥ 5 years ago with no subsequent evidence of recurrence.
 Major surgery within 4 weeks prior to randomisation.
 Cardiovascular illness or complication which, in Investigator’s judgment, compromises prognosis at 6 months or prevents the patient from following study procedures, including a recent history of stroke or myocardial infarction or presence of NYHA class III-IV heart failure or severe arrhythmia.
 Serious (NCI CTCAE grade 3-4) uncontrolled infection.
 Known presence of active autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, Crohn's Disease, multiple sclerosis, ankylosing spondylitis).
 Known presence of acquired, hereditary, or congenital immunodeficiency, (e.g. cellular immunodeficiencies, hypogammaglobulinemia, dysgammaglobulinemia).
 HIV infection.
 Current need for immunosuppressive drug therapy, including systemic corticosteroids. Previously exposed patients are eligible following a wash-out period ≥4 weeks before randomisation.
 Current need for denosumab therapy. (Patients under bisphosphonate treatment are eligible).
 Skin disease interfering with evaluation of local tolerance of GX301 injections.
 Any condition which, in the judgment of the Investigator, would place the subject at undue risk or interfere with the results of the study.
 Inability to regularly access centre facilities for logistical or other reasons.
 Participation in any interventional drug or medical device study within 30 days prior to treatment start.

E.5 End points

E.5.1

Primary end point(s)

proportion of patients achieving immunological response:
A panel of three immunological tests will be performed on blood samples taken at baseline and on Days 90 and 180 (or upon trial discharge if earlier than on Day 180). All tests will be performed at the central immunology laboratory. Operators will be unaware of the GX301 regimen assigned to each patient.
Immunological tests will be as follows: Elispot assay; intracellular staining and flow cytometry (for both CD4+ and CD8+ T cells); cytotoxic assay.
The immunological outcome of each patient will be represented by a 6-response matrix including positive responses, either absent at baseline or greater than twice the baseline, achieved in the three tests at Days 90 and 180. The outcome will be scored as the sum of positive responses in the matrix (score range: 0 to 6).
Patients will be classified as immunological responders if achieving a score ≥3. Assessable patients will be those in whom ≥3 positive responses or ≥4 negative responses have been shown.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 26 / day 180

E.5.2

Secondary end point(s)

Time-course of PSA (central laboratory).
Maximum PSA change from baseline occurring at any time of the observation period.
Changes from baseline in cancer-related symptoms, FACT-P functional assessment and consumption of analgesic drugs.
Time from randomisation to disease progression (progression-free survival).
Time from randomisation to patient death (overall survival), as derived from on-study and follow-up data.

E.5.2.1

Timepoint(s) of evaluation of this end point

up to week 104 / day 720

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

three treatment regimens of the same IMP are tested

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

the trial ends with a follow up scheduled for week 104 / day 720. this does not imply a visit of the subject, but a contact to assess the vital status. the last subject last visit (LSLV) will be performed at week 78 / day 540.

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)

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

F.2 Gender

F.2.1

Female

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

120

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)

none

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

2014-07-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-03

P. End of Trial
P.	End of Trial Status	Completed

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