Clinical Trials Register

Summary
EudraCT Number:	2010-024342-30
Sponsor's Protocol Code Number:	CBYM338X2202
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:	2011-06-07
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

UK - MHRA

A.2

EudraCT number

2010-024342-30

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled multi-center study of BYM338 for treatment of cachexia in patients with stage IV non-small cell lung cancer or stage III/IV adenocarcinoma of the pancreas

A.3.1

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

A safety and efficacy clinical study of the investigational medicinal product BYM338 for the treatment of unintentional weight loss in patients with cancer of the lung or the pancreas

A.4.1

Sponsor's protocol code number

CBYM338X2202

A.5.4

Other Identifiers

Name:

Not applicable

Number:

Not applicable

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	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharmaceutials UK Ltd
B.5.2	Functional name of contact point	Medical Information Services
B.5.3	Address:
B.5.3.1	Street Address	Frimley Business Park, Frimley
B.5.3.2	Town/ city	Camberley, Surrey
B.5.3.3	Post code	GU16 7SR
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4101276698370
B.5.5	Fax number	+4110276698449
B.5.6	E-mail	medinfo.uk@novartis.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	BYM338
D.3.2	Product code	BYM338
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	BYM338
D.3.9.3	Other descriptive name	Human Monoclonal Antibody blocking ActRIIB
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	150
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	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Condition of cachexia in adults with stage IV metastatic non-small cell lung cancer or stage III/IV pancreatic adenocarcinoma.

E.1.1.1

Medical condition in easily understood language

Condition of unintentional weight loss in adults with lung cancer or pancreas cancer.

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10064015
E.1.2	Term	Cancer cachexia
E.1.2	System Organ Class	100000004861

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 assess the preliminary efficacy of a single intravenous dose of BYM338 in increasing thigh muscle volume as assessed by Magnetic Resonance Imaging compared to placebo.

E.2.2

Secondary objectives of the trial

To assess the safety and tolerability of intravenous BYM338 in this patient population.

To assess the preliminary efficacy of intravenous BYM338 in treating unintentional weight loss compared to placebo.

To obtain preliminary pharmacokinetic data for intravenous BYM338 in this patient population.

To assess the preliminary efficacy of intravenous BYM338 in improving total lean body mass and total bone mineral density by Dual-Energy X-ray Absorptiometery compared to placebo.

To assess the preliminary efficacy of a single intravenous dose of BYM338 in improving daily physical activity levels (using the ActivPAL™ device) compared to placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained before any assessment is performed.

2. Adult men and women >18 years of age with pathologically and/or clinically confirmed diagnosis of stage IV non-small (squamous or non-squamous) cell lung cancer (NSCLC) or stage III/IV adenocarcinoma of the pancreas.

3.Patients with stage IV NSCLC will be receiving , or completed, or discontinued standard chemotherapy, or be chemo-naive by choice.

4.Patients with stage III/IV pancreatic adenocarcinoma will be receiving standard chemotherapy, , or no chemotherapy. If patients are receiving chemotherapy, a change in chemotherapy is not expected.

5.Patients receiving chemotherapy must be tolerating it with respect to nausea/vomiting/anorexia symptoms and demonstrate adequate dietary intake before starting the study drug.

6. ≥5% unintentional weight loss from patient reported pre-illness weight at Screening or Baseline visits, occuring over the previous 3-6 months and not explained by simple starvation.

7. In patients with 2+ or greater pitting edema of the legs, documented weight loss > 2% over 4 weeks, not due to diuretic therapy, is acceptable.

8. Body mass index ≤ 30 kg/m2. Body mass index = mass (kg)/(height in meters)2 at screening.

9. Eastern Cooperative Oncology Group Performance Status of 0, 1 or 2 at screening and baseline.

10. Life expectancy of >4 months based on judgment of enrolling physician.

11. Literate and able to communicate well with the investigator and team depending on country of study, to understand and comply with the requirements of the study including by phone encounters and written logs.

E.4

Principal exclusion criteria

1. Patients who have received investigational anti-neoplastic therapy within 3 weeks of screening, or for any other limitation of participation in an investigational trial based on local regulations.

2. a. Expected to receive Avastin (bevacizumab) therapy or have received within 8 weeks of the Baseline visit.

2.b. Received radiation therapy within 4 weeks of the Baseline visit, or expected to require radiation therapy during the 8 week Core phase of the study.

2.c. Major surgery within the past 3 weeks prior to the Screening visit.

2.d. Use of oral corticosteroids >20 mg/d prednisone equivalent, unless used in pulse form for chemotherapy-related symptoms such as nausea/vomiting.

2.e. Within 4 weeks of baseline visit, use of medications for weight loss (incl. megestrol acetate, androgens, beta agonists).

3. Severe nausea/vomiting/anorexia/mucositis/steatorrhea/uncontrolled pain or gastrointestinal disorder, intestinal or biliary obstruction, or other reason that causes enteral energy intake <20 kcal/kg/day and protein intake of <0.6 g/kg/d (estimated from 2-day food record at screening). Dietary intake may be ascertained again within 1 to 2 weeks after intensive nutritional counseling.

4. Evidence of inadequate organ function, as defined by the following parameters at screening: Bone marrow: ANC <1.0 x 10_9/L, platelets <75 x 10_9/L; Hepatic function: serum total bilirubin >3 x ULN, AST and ALT >5 x ULN; Pancreatic function: serum amylase or lipase >5 x ULN and evidence of uncontrolled exocrine pancreatic dysfunction (pain, nausea, vomiting, steatorrhea, radiographic evidence of pancreatic or common bile duct obstruction). For patients with pancreatic adenocarcinoma, imaging report of moderate-severe bile duct dilatation; Renal function: GFR <30 mL/min, estimated from the MDRD equation; CNS: Evidence of clinically significant brain metastases requiring high dose corticosteroid therapy or causing uncontrolled seizures, mental status changes, anorexia, nausea or vomiting.

5. At screening and baseline, vital signs will be assessed in the supine position after subject has rested for at least 3 minutes and again after three (3) minutes in the standing position. Vital signs outside the ranges specified below are exclusionary: Oral body temperature: <35.0 or >38 °C; (>38.5 °C if evaluation for infection is negative and fever is thought to be related to tumor). Systolic blood pressure: <70 mm Hg. Symptomatic orthostatic hypotension.

6. Patients with concurrent severe and/or uncontrolled medical conditions that could compromise participation in the study (e.g. myocardial infarction within the past 3 months; congestive heart failure requiring medical treatment; uncontrolled hypertension or diabetes mellitus; severe pancreatitis; clinically significant neurologic or psychiatric disorder; immunodeficiency, active or uncontrolled infection), uncontrolled pain, other non-stable comorbidities.

7. Pregnant or lactating women.

8. Women of child-bearing potential must use highly effective contraception during the study and for 14 weeks after stopping treatment. Highly effective contraception is defined as either: a. Total abstinence [Periodic abstinence and withdrawal are not acceptable]. b. Surgical bilateral oophorectomy with/without hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status has been confirmed by follow up hormone level assessment. c. Male partner sterilization with post-vasectomy documentation of the absence of sperm in the ejaculate). d. Use of (a+b) or (a+c) or (b+c): a. Oral, injected or implanted hormonal contraception methods. b. Intrauterine device or system. c. Condom or Occlusive cap (diaphragm, cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. In case of use of oral contraception women should have been stable on same pill for minimum of 3 months before taking study treatment. Postmenopausal females (no regular menstrual bleeding for at least 1 year prior to initial dosing). Menopause confirmed by plasma FSH level (>40 IU/L) or as determined by the cut off used by the local laboratory at screening. Female patients who report surgical sterilization must have had the procedure at least 6 months prior to initial dosing. Surgical sterilization should be supported with clinical documentation made available to sponsor and noted in the eCRF. Female patients must have negative pregnancy test results at screening/baseline. Additional pregnancy tests will be performed (week 8 and 16).

9. Patients unwilling or unable to comply with the protocol.

10. Patients with known claustrophobia, double above-knee leg amputee, presence of pacemaker and/or ferromagnetic material in the body that prohibits MRI.

E.5 End points

E.5.1

Primary end point(s)

Superiority of BYM338 compared to placebo in thigh muscle volume.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 8.

E.5.2

Secondary end point(s)

Safety and tolerability of a single intravenous dose of BYM338.

Preliminary efficacy of a single intravenous dose of BYM338 in treating unintentional weight loss.

Preliminary pharmacokinetic data of a single intravenous dose of BYM338.

Improving total lean body mass and bone mineral density.

Preliminary efficacy of a single intravenous dose of BYM338 in improving daily physical activity levels (using the ActivPAL™ device).

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 8.

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

Yes

E.6.11

Pharmacogenomic

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

Switzerland

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 in the extension study.

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