Clinical Trials Register

Summary
EudraCT Number:	2014-004510-28
Sponsor's Protocol Code Number:	IM-201
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-09-23
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2014-004510-28

A.3

Full title of the trial

An open-label, randomized, controlled, multicenter, phase II study evaluating safety and efficacy of intratumorally administered Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy, compared to Sunitinib post-nephrectomy in metastatic renal cell carcinoma patients

A.3.1

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

A clinical study to evaluate safety and efficacy of a new vaccine in combination with standard treatment compared to standard treatment in patients with metastatic renal cancer

A.4.1

Sponsor's protocol code number

IM-201

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	Immunicum AB
B.1.3.4	Country	Sweden
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	Immunicum AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Immunicum AB
B.5.2	Functional name of contact point	Management
B.5.3	Address:
B.5.3.1	Street Address	Grafiska vägen 2
B.5.3.2	Town/ city	Gothenburg
B.5.3.3	Post code	SE-412 63
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46 31 41 50 52
B.5.6	E-mail	info@immunicum.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	Intuvax
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intratumoral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ilixadencel
D.3.9.2	Current sponsor code	Intuvax
D.3.9.3	Other descriptive name	ALLOGENEIC PROINFLAMMATORY DENDRITIC CELLS
D.3.9.4	EV Substance Code	SUB176412
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	8500000 to 10000000
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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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	Yes
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	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	Sutent
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Sutent
D.3.4	Pharmaceutical form	Capsule, hard
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	SUNITINIB
D.3.9.1	CAS number	557795-19-4
D.3.9.4	EV Substance Code	SUB22321
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	50
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

Metastatic Renal Cell Carcinoma

E.1.1.1

Medical condition in easily understood language

Advanced Kidney cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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 objectives are:
- To evaluate median overall survival (OS) from randomization in
metastatic renal cell carcinoma (mRCC) patients overall and by
subgroup, i.e. in high-risk and in intermediate-risk patients separately,
receiving two (2) vaccine doses of Intuvax pre-nephrectomy, followed
by sunitinib initiated five (5) to eight (8) weeks post-nephrectomy and
in non-vaccinated mRCC patients receiving sunitinib initiated five (5) to
eight (8) weeks post-nephrectomy
- To evaluate 18-month survival rate from randomization in mRCC
patients overall and by subgroup, i.e. in high-risk and in intermediaterisk
patients separately, receiving two (2) vaccine doses of Intuvax prenephrectomy
followed by sunitinib post-nephrectomy and in nonvaccinated
patients receiving sunitinib post-nephrectomy

E.2.2

Secondary objectives of the trial

The secondary objectives are (to be evaluated in vaccinated and nonvaccinated
patients overall, and in each subgroup (intermediate- and
high risk patients) :
- To evaluate safety and tolerability
- To evaluate PFS according to Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 criteria from Sunitinib Start Visit
- To evaluate response and its duration according to RECIST 1.1 criteria
from Sunitinib Start Visit
- To evaluate time to progression (TTP) from Sunitinib Start Visit
- To evaluate the number of infiltrating CD8+ T-cells in available
diagnostic pre-biopsy (sample from either primary tumor or metastasis
acceptable) and in the resected primary renal tumor

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Newly (<6 months) diagnosed RCC (histological/cytological verification is optional) with at least one (1) CT-verified metastasis ≥10 mm for which complete metastasectomy is not planned. US patients
must have verified clear-cell tumor histology
2) Planned resection of primary tumor
3) Primary tumor diameter ≥40 mm
4) Candidate for first-line therapy with sunitinib initiated five (5) to eight (8) weeks after nephrectomy
5) Female or male ≥18 years of age
6) Willing and able to provide informed consent
7) Adequate hematological parameters, i.e.:
• B-Leukocyte count ≥4.5 x109/L
• B-Platelet count ≥150 x109/L
• B-Hemoglobin (Hb) ≥90 g/L
8) Serum-creatinine and serum-bilirubin ≤1.5 × ULN. Serum-ALAT and serum-ASAT ≤2.5 × ULN (or ≤5 in case of liver metastases)
9) Female who has been post-menopausal for more than one (1) year or female of childbearing potential agreeing to use a highly efficient method of contraception (i.e. a method with less than 1% failure rate [e.g. sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner or combined birth control pills]) from Screening until 90 days after last dose of Intuvax and/or until completed sunitinib treatment whichever occurs later. Female of childbearing potential must have a negative blood pregnancy test at Screening, and if randomized to vaccination a negative blood or urine pregnancy test within one (1) day before each dose of Intuvax) and must not be lactating
or
Male agreeing to use condoms from Screening until 90 days after last dose of Intuvax and/or until completed sunitinib treatment whichever occurs later, or male having a female partner who is using a highly efficient method of contraception as described above

E.4

Principal exclusion criteria

1) Life expectancy less than 4 months
2) Central nervous system (CNS) metastasis that is symptomatic or
progressing or untreated or that requires current therapy (e.g. evidence
of new or enlarging CNS metastasis or new neurological symptoms
attributable to CNS metastases)
3) Active autoimmune disease which requires treatment with systemic immunosuppressive agents, e.g. inflammatory bowel disease, multiple sclerosis, sarcoidosis, psoriasis, autoimmune hemolytic anemia, rheumatoid arthritis, SLE, vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other rheumatological diseases
4) Treatment with per oral systemic corticosteroids exceeding 10
mg/day within 7 days before Screening until Nephrectomy (inhaled,
intranasal, and local steroids acceptable irrespective of dose)
5) Known cardiomyopathy and/or clinically significant abnormal ECG
findings at Screening disqualifying the patient from nephrectomy and
subsequent sunitinib treatment
6) Karnofsky performance status <70%
7) National Cancer Institute (NCI) Common Terminology criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within 28 days before Screening
8) Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
9) Clinically significant gastrointestinal abnormalities
10) Uncontrolled hypertension, or uncontrolled diabetes mellitus
11) Pulmonary embolism within 12 months before Screening
12) Prior history of invasive cancer within 5 years before Screening,
except for adequately treated in situ carcinomas or non-melanoma skin
cancer
13) Ongoing infection that requires parenteral treatment with antibiotics
14) Active or latent virus disease (HIV, HBV and HCV)
15) ECOG performance status >2 after optimization of analgesics
16) Abnormal or clinically significant coagulation parameters at the
discretion of the investigator, i.e.:
• Prothrombin Time - International Normalized Ratio (PT-INR)
• Activated Partial Thromboplastin Time (APTT)
Patients being treated with anticoagulants are excluded if the
coagulation parameters are outside the therapeutic intervals as
described in the SmPC/USPI for the administered treatment
17) Known major adverse reaction/event in connection with previously made vaccination (e.g. asthma, anaphylaxis or other serious reaction)
18) Known hypersensitivity or allergy to sunitinib or to chemically
related products or likely to be exacerbated by any component of the
study products
19) Prior systemic antitumor therapy within 28 days before Screening Visit. However, local radiation therapy to any area except for the abdominal/retroperioneal area including the kidney tumor is allowed
20) Exposure to other investigational products within 28 days prior to Screening Visit
21) Patients on anticoagulants for whom temporarily stop and start,
supported by low molecular weight heparin (or other anticoagulation
therapy at the discretion of the Investigator and/or per local standard of
care) during vaccination and nephrectomy, is not an option
22) History of alcohol or substance abuse
23) Any reason that, in the opinion of the Investigator, contraindicates that the patient participates in the study

E.5 End points

E.5.1

Primary end point(s)

- OS from randomization overall in mRCC patients and by each subgroup,
i.e. in high-risk and in intermediate-risk mRCC patients
- 18-month survival rate from randomization overall in mRCC patients
and by each subgroup, i.e. in high-risk and in intermediate-risk mRCC
patients

E.5.1.1

Timepoint(s) of evaluation of this end point

End of study (week 78)

E.5.2

Secondary end point(s)

- Frequency and proportion of AEs including clinical significant changes
in laboratory tests and vital signs from Screening
- PFS from start of sunitinib according to RECIST 1.1
- Proportion of Objective Response Rate (ORR) from start of sunitinib
treatment and duration of response in each subgroup
- TTP from start of sunitinib treatment
- Relative number of tumor infiltrating CD8+ T-cells in the resected
primary tumor compared to relative number of infiltrating CD8+ T-cells
in available diagnostic pre-biopsy (sample from either primary tumor or
metastasis acceptable)

E.5.2.1

Timepoint(s) of evaluation of this end point

End of study (week 78)

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

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

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)

Intuvax is an investigational medicinal product under development and will consequently not be available for treatment of the patients after study completion.
Immunicum AB will pay the patients Sunitinib treatment during their participation in the study.
After end of study participation, patients will continue treatment in accordance with clinical praxis

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

2015-12-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-06-17

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