Clinical Trials Register

Summary
EudraCT Number:	2008-006778-14
Sponsor's Protocol Code Number:	BT-CL-PGG-LCA0822
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-12-03
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

Germany - BfArM

A.2

EudraCT number

2008-006778-14

A.3

Full title of the trial

A Phase 2, Randomized, Efficacy and Safety Study of Imprime PGG® Injection in Combination with Cetuximab and Concomitant Paclitaxel and Carboplatin Therapy in Patients with Previously Untreated Advanced (Stage IIIB or IV)
Non-Small Cell Lung Cancer

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

BT-CL-PGG-LCA0822

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	Biothera
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	Biothera
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	Ecron Acunova
B.5.2	Functional name of contact point	Bettina Weiher
B.5.3	Address:
B.5.3.1	Street Address	Breitenbachstr. 23
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13509
B.5.3.4	Country	Germany
B.5.4	Telephone number	+493041478611
B.5.5	Fax number	+493041478629
B.5.6	E-mail	bettina.weiher@ecronacunova.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	Imprime PGG (PGG Beta Glucan)
D.3.2	Product code	BTH 1677
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 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	Yes
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	Erbitux
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck KGaA, Germany
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.3.1	Product name	Cetuximab
D.3.2	Product code	L01XC06
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.3.11 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	Cetuximab is a chimeric monoclonal IgG1 antibody prodcued in a mammalian cell line (Sp2/0) by recombinant DNA technology
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	Information not present in EudraCT
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	Paclitaxel
D.3.2	Product code	L01CD01
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 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: 4
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	Carboplatin
D.3.2	Product code	L01XA02
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.3.11 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

Patients with Previously Untreated Advanced (Stage IIIB or IV)
Non-Small Cell Lung Cancer

E.1.1.1

Medical condition in easily understood language

Patients with Previously Untreated Advanced (Stage IIIB or IV)
Non-Small Cell Lung 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	PT
E.1.2	Classification code	10029522
E.1.2	Term	Non-small cell lung cancer stage IV
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	10029521
E.1.2	Term	Non-small cell lung cancer stage IIIB
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	10061773
E.1.2	Term	Coagulation factor VIII level abnormal
E.1.2	System Organ Class	10022891 - Investigations

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 objectives of this study are to assess the antitumor activity and safety of Imprime PGG® Injection (Imprime PGG) when used in the treatment of non-small cell lung cancer (NSCLC) patients.
The primary objective of this study is:
• To determine the objective response rate (ORR) in each study arm

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are:
• To determine the disease control rate (DCR) in each study arm
• To determine the overall survival (OS) in each study arm
• To determine the complete response (CR), partial response (PR), and stable disease (SD) rates in each
study arm
• To determine the duration of objective tumor response in each study arm
• To determine the duration of stable disease in each study arm
• To determine the duration of time to progression (TTP) in each study arm
• To assess the safety of the dosing regimen in each study arm
• To determine the pharmacokinetic (PK) profile of Imprime PGG (in active treatment arm only)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To be considered eligible to participate in the study, a subject must meet all of the inclusion criteria listed below.
The subject:
1. Has read, understood and signed the informed consent form (ICF) approved by the Independent Review
Board/Ethics Committee (IRB/EC);
2. Is between the ages of 18 and 75 years old, inclusive;
3. Has histologically or cytologically confirmed stage IIIB (malignant pericardial or pleural effusion) or stage
IV non-small cell lung cancer;
4. Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to
RECIST;
5. Has an ECOG performance status of 0 or 1;
6. Has a life expectancy of > 3 months;
7. Has adequate hematologic function as evidenced by:
a. ANC ≥ 1,500/μL
b. PLT ≥ 100,000/μL
c. HGB ≥ 9 g/dL
obtained within 1 week prior to the first dose of study medication;
8. Has adequate renal function as evidenced by:
a. Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) for the reference lab
b. Urine dipstick for proteinuria of < 1+ (i.e., either 0 or trace) within 2 weeks of Day 1
If urine dipstick is ≥ 1+, then urine protein excretion must be ≤ 500 mg over a 24 hour collection
obtained within 1 week prior to the first dose of study medication;
9. Has adequate hepatic function as evidenced by:
a. Serum total bilirubin ≤ 1.0 mg/dL
b. AST ≤ 2.5X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
c. ALT ≤ 2.5X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
obtained within 1 week prior to the first dose of study medication;
10. If a woman of childbearing potential or a fertile man (and his partners), must agree to use an effective form
of contraception (hormonal contraceptive, double-barrier method or abstinence) during the study.

E.4

Principal exclusion criteria

To be eligible for entry into the study, the subject must not meet any of the exclusion criteria listed below.
The subject:
1. Has received prior systemic chemotherapy at any time for lung cancer;
2. Has received previous radiation therapy to >30% of active bone marrow or any radiation therapy within 3
weeks of Day 1;
3. Has a known hypersensitivity to baker’s yeast, or has an active yeast infection;
4. Has had previous exposure to Betafectin® or Imprime PGG;
5. Has an active infection;
6. Presents with any of the following medical diagnoses/conditions at the time of screening:
a. Central nervous system (CNS) metastases
b. Peripheral neuropathy ≥ grade 2 from any cause
c. Fever of >38.5° C within 3 days prior to screening or Day 1, initial dosing
d. Known HIV/AIDs, Hepatitis B, Hepatitis C, connective tissue or autoimmune disease, or other
clinical diagnosis, ongoing or intercurrent illness that in the physician’s opinion could interfere
with participation
7. Has a history of any of the following medical diagnoses/conditions:
a. Myocardial infarction or an unstable or uncontrolled disease or condition related to or impacting
cardiac function (e.g., unstable angina, congestive heart failure) within the previous 6 months
b. Second malignancy within the previous 5 years, other than basal cell carcinoma, cervical intraepithelial
neoplasia or curatively treated prostate cancer with a PSA of <2.0 ng/mL
8. Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab;
9. Has a know sensitivity to Cremophor EL;
10. Has previously received treatment with cetuximab;
11. If female, is pregnant or breast-feeding;
12. Is receiving concurrent investigational therapy or has received investigational therapy within a period of 30
days prior to the first scheduled day of dosing (investigational therapy is defined as treatment for which
there is currently no regulatory-authority-approved indication);
13. Has previously received an organ or progenitor/stem cell transplant.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is:
• Objective response rate (ORR) in each study arm

E.5.1.1

Timepoint(s) of evaluation of this end point

at least 4 completed cycles of three weeks each (total 12 weeks) and maximum of 18 cycles (total 54 weeks), before a subsequent Sponsor authorization is required in order to continue treatment under the protocol.

E.5.2

Secondary end point(s)

The secondary endpoints of this study are:
• Disease control rate (DCR) for each study arm
• Overall survival (OS) for each study arm
• Complete response (CR), partial response (PR), and stable disease (SD) rates in
each study arm
• Duration of objective tumor response in each study arm
• Duration of stable disease in each study arm
• Duration of time to progression (TTP) in each study arm

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

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)

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

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

Information not present in EudraCT

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

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)

Patients who continue to experience a stable, partial or complete response (according to RECIST 1.0) following completion of the 18th treatment cycle, will be evaluated on a case-by-case basis by the investigator, the Medical Monitor and the study Sponsor to determine eligibility for extending their treatment under this protocol.
Following completion of the treatment phase of the study, subjects will be contacted monthly for survival up until death or subject being lost to follow-up.

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

2009-03-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-03-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-03-08

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IMP with orphan designation in the indication
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