Clinical Trials Register

Summary
EudraCT Number:	2009-013421-42
Sponsor's Protocol Code Number:	APG101_CD_002
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-07-07
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 - PEI

A.2

EudraCT number

2009-013421-42

A.3

Full title of the trial

A phase II, randomized, open-label, multi-centre study of weekly APG101 + reirradiation versus reirradiation in the treatment of patients with first or second progression of glioblastoma

A.3.1

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

APG101 in glioblastoma

A.3.2

Name or abbreviated title of the trial where available

APG101 in glioblastoma

A.4.1

Sponsor's protocol code number

APG101_CD_002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01071837

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	Apogenix GmbH
B.1.3.4	Country	Germany
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	Apogenix GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Apogenix GmbH
B.5.2	Functional name of contact point	Dr. Claudia Kunz
B.5.3	Address:
B.5.3.1	Street Address	Im Neuenheimer Feld 584
B.5.3.2	Town/ city	Heidelberg
B.5.3.3	Post code	69120
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4962215860824
B.5.5	Fax number	+4962215860824
B.5.6	E-mail	claudia.kunz@apogenix.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	EU/3/09/709
D.3 Description of the IMP
D.3.1	Product name	APG101
D.3.2	Product code	APG101
D.3.4	Pharmaceutical form	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	not assigned
D.3.9.1	CAS number	not assigned
D.3.9.2	Current sponsor code	APG101
D.3.9.3	Other descriptive name	Recombinant fusion protein consisting of the extracellular portion of CD95 fused to the Fc part of a human IgG1 molecule (APG101)
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	10
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	Recombinant fusion protein consisting on extracellular domain of CD95 fused to the Fc part of human IgG1 molecule

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

Glioblastoma Multiforme (first or second progression)

E.1.1.1

Medical condition in easily understood language

Glioblastoma multiforme, a highly malignant brain tumour

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	PT
E.1.2	Classification code	10018336
E.1.2	Term	Glioblastoma
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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10018337
E.1.2	Term	Glioblastoma multiforme
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

6 months rate of progression free survival (PFS6)

E.2.2

Secondary objectives of the trial

•Safety and tolerability of APG101
•Progression-free survival
•Objective response rates (OR)
•Duration of response (DR) in responders
•Overall survival
•Quality of life as determined by EORTC QLQ-C15 PAL and the EORTC brain module QLQ-BN 20
•Cognitive function determined by MMSE

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Signed Informed Consent
•Male and female patients with a local recurrence / progression of glioblastoma and either not being eligible for tumour resection or having macroscopic residual tumour after resection of the recurrence
•Not more than two prior therapy regimens including one or two resections, one or two chemotherapies, of which one must have been TMZ-containing and one radiotherapy for the brain tumour
•Diagnosis of glioblastoma must be proven histologically and progress / recurrence of glioblastoma must be documented by MRI. MRI images must not be older than 2 weeks before randomisation / start of RT
•Candidate for reirradiation with recurrent tumour visible on MRI-T1 (Gd) and with the largest diameter measuring 1 to 4 cm
•Previous irradiation therapy of the primary tumour with a maximal dose of 60 Gy
•At least 8 months since the end of preirradiation
•at least 18 years old, smoking or non-smoking, of any ethnic origin
•Karnofsky performance index (KPI) ≥ 60%
•Suitable veins or existing port system for intra-venous infusion
•adequate contraception
•Stable or decreasing treatment with steroids within 5 days before treatment start
•Laboratory results (urine, blood count, chemistry, creatinine) without clinically significant abnormalities or
Neutrophile counts > 1 500/μl
Platelet counts > 80 000/μl
Haemoglobin > 10 g/dl
Serum creatinine < 1.5-fold upper normal range
Bilirubin, ASAT or ALAT < 2,5-fold upper normal range unless attributed to anticonvulsants
Alkaline phosphatase < 2,5-fold upper normal range

E.4

Principal exclusion criteria

•Unable to give informed consent for this study
•Unable to undergo MRI
•Prior second radiotherapy of brain, prior first radiotherapy with more than 60 Gy
•Prior treatment with bevacizumab
•Prior treatment with iodine seeds and brachytherapy
•Doses to organs at risk defined by Dogan et al. (2003) exceeded or reached by prior radiation therapy; e.g. cumulative total dose on the optical chiasm >54 Gy for 2 Gy/fraction, α/β=2
•Treatment within in any other clinical trial parallel to the treatment phase of the current study or within 30 days before inclusion
•Known coronary artery disease, significant cardiac arrhythmias or severe congestive heart failure (NYHA class III – IV)
•Positive test results for HbsAG, anti-HCV, anti-HIV-1/-2
•Any other condition or treatment that, in the opinion of the Investigator, might interfere with the study or current drug or substance abuse
•Past medical history of diseases with poor prognosis according to the judgement of the Investigator, e.g. severe coronary heart disease, severe diabetes, immune deficiency, residual deficits after stroke, severe mental retardation
•Inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study
•Unlikely to comply with the protocol requirements, instructions and study-related restrictions; e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study
•Pregnancy or breast feeding
•Subject is the investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.
•Vulnerable patients

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint is number of patients beeing progression free after 6 month (PFS6).
Patients with a confirmed PFS time of at least 6 month will be defined as responders. Progression free survival (PFS) is defined as time from randomization until death or disease progression according to Macdonald criteria.

E.5.1.1

Timepoint(s) of evaluation of this end point

At first interims analysis (after 28 patients have been included and treated for 6 month) and at the end of the study

E.5.2

Secondary end point(s)

Safety and tolerability of APG101
• Progression-free survival
• Objective response rates (OR)
• Duration of response (DR) in responders
Recurrence pattern analysis
• Overall survival
• Quality of life as determined by EORTC QLQ-C15 PAL and the EORTC brain module QLQ-BN 20.
• Cognitive function determined by MMSE

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end 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

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

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

reirradiation (standard of care)

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

Austria

Germany

Russian Federation

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

Patients can stay in the trial as long as they benefit.

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