Clinical Trials Register

Summary
EudraCT Number:	2006-003709-15
Sponsor's Protocol Code Number:	20050219
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-12-18
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

Denmark - DHMA

A.2

EudraCT number

2006-003709-15

A.3

Full title of the trial

A Double-Blind, Randomized, Placebo-controlled Study of Two Different Schedules of Palifermin (Pre- and Post Chemotherapy and Pre-Chemotherapy only) for Reduction in Severity of Oral Mucositis in Subjects with Multiple Myeloma (MM) Receiving High Dose Melphalan followed by Autologous Peripheral Blood Stem Cell Transplantation (PBSCT)

A.3.1

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

A study comparing two different dosing regiments of palifermin (before and after chemotherapy versus before chemotherapy) with placebo on the effect of reducing oral mucositis in patients with multiple myeloma who have been given treatment with high dose melphalan followed by stem cell transplantation.

A.4.1

Sponsor's protocol code number

20050219

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00434161

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	Swedish Orphan Biovitrum AB (publ)
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	Swedish Orphan Biovitrum AB (publ)
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	Swedish Orphan Biovitrum AB (publ)
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Tomtebodavägen 23 A
B.5.3.2	Town/ city	Stockholm
B.5.3.3	Post code	11276
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46 (0) 8 6972000
B.5.5	Fax number	+46 (0) 8 6972330
B.5.6	E-mail	clinical@sobi.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	Yes
D.2.1.1.1	Trade name	Kepivance
D.2.1.1.2	Name of the Marketing Authorisation holder	Swedish Orphan Biovitrum AB (publ)
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	palifermin
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Palifermin
D.3.10	Strength
D.3.10.1	Concentration unit	µg/kg microgram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
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	Powder for solution for injection
D.8.4	Route of administration of the placebo	Intravenous bolus use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Oral Mucositis Induced by High Dose Chemotherapy

Cataract development associated with palifermin administration

E.1.1.1

Medical condition in easily understood language

Oral mucositis (soreness, dryness and inflammation of the mouth) which is a common side effect of certain cancer treatments (such as chemotherapy and radiotherapy).

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	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10028130
E.1.2	Term	Mucositis oral
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10007739
E.1.2	Term	Cataract
E.1.2	System Organ Class	10015919 - Eye disorders

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 the efficacy of palifermin relative to placebo when given either pre- and post-high dose chemotherapy or pre- high dose chemotherapy only with regard to the severity of oral mucositis (WHO grades 0/ 1, 2, 3 or 4)
Primary Cataract Evaluation Objectives:
To assess cataract development or progression at month 12 based on an increase of ≥ 0.3 in the Lens Opacities Classification System III (LOCS III) score for either posterior subcapsular cataract (P), cortical cataract (C), or nuclear opalescence (NO) (Chylack LT et al 1993).

E.2.2

Secondary objectives of the trial

To assess the effect of palifermin on the incidence and duration of ulcerative oral mucositis (WHO grades 2, 3 and 4) and of severe mucositis (WHO grades 3 and 4)
To evaluate the impact of palifermin on patient-reported mouth and throat soreness (MTS)
Cataract Eval Objectives - To assess:
-effect of palifermin on the change of posterior subcapsular cataract (P) using the Lens Opacities Classification System III (LOCS III) score.
-effect of palifermin on the change of cortical cataract (C) using the Lens Opacities Classification System III (LOCS III) score.
-effect of palifermin on the change of nuclear opalescence (NO) using the Lens opacities Classification System III (LOCS III) score.
-effect of palifermin on the incidence of decreased best corrected visual acuity (BCVA) from the baseline BCVA on the ETDRS (“Early Treatment Diabetic Retinopathy Study”) chart, (Ferris III FL et al 1982, Ferris III FL et al 1993, Ferris III FL et al, 1996, Ferris III FL, Sperduto RD 1982).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Multiple myeloma (MM) subjects scheduled to receive high-dose Melphalan (200 mg/m2 if creatinine clearance ≥ 30 mL/min or 140 mg/m2 if creatinine clearance < 30 mL/min), in a one day schedule (day -2) followed by autologous PBSCT (day 0)
• Age ≥ 18 years and ≤ 70 years
• BMI ≤ 35
• ECOG performance status ≤ 2, or an ECOG status of 3 if the reason for a status of 3 is due exclusively due to MM (e.g. pathological fracture)
• Adequate pulmonary function as measured by a corrected carbon monoxide (CO) diffusing capacity (DLCO) ≥ 50% of predicted
• Minimum of 2.0 x 106 CD34+ cells/kg collected for autologous transplantation
• Adequate hematological function (ANC ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L)
• Total bilirubin ≤ 2 mg/dL
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 4.0 x IULN
• Negative serum or urine pregnancy test for women of child bearing potential within 14 days prior to enrolment
• Each subject must give informed consent directly or through a legally acceptable representative before participating in any study specific procedure, or receiving any study medication

Cataract specific:
All subjects eligible for 20050219 will also be assessed for their eligibility for cataract
assessment procedures. If a subject is not eligible for cataract assessment procedures, or the site has a waiver from Amgen regarding cataract assessments, the subject may still be eligible for inclusion in the study but will be exempt from the cataract assessments.
• Subjects at minimum with a baseline best corrected visual acuity (BCVA) of 20/40, (6/12 or 0.5 on the decimal scale) or better using the ETDRS chart in one eye
• Subject at minimum with one eye with a natural, intact lens
• Subject who has a LOCS III score at baseline of P < 1.0, C < 2.0 and NO < 2.0
(in at least one eye)

E.4

Principal exclusion criteria

• History of or concurrent malignancy other than MM, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin, in situ cervical carcinoma, or other surgically cured malignancy, without evidence of disease for > 3 years
• Prior treatment with palifermin, or other fibroblast or keratinocyte growth factors
(eg, KGF-2)
• Prior autologous or allogeneic transplants
• Currently active infection of oral mucositis
• Oral abnormalities defined as baseline oral assessment of WHO grade > 0
• Receiving dialysis
• Twenty-eight days or less between receiving any other investigational drug or device and randomization into this study
• Subject of child-bearing potential is evidently pregnant (eg, positive HCG test) or is breast feeding
• Subject has not agreed to using adequate contraceptive precautions
• Known to be sero-positive for human immunodeficiency virus (HIV), hepatitis B virus (HBSAg+), or hepatitis C virus (HCV)
• Subject has known sensitivity to any of the products to be administered during dosing, including E coli-derived products
• Subject has previously been treated on this study
• Unwilling or unable to complete the patient-reported outcome questionnaires
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

Cataract specific:
• History of cataract surgery in both eyes
• Incapable of being responsive to midriatic agents (minimum of approximately a 6
mm pupil required)
• History of other ocular disease leading to visual loss (e.g., macular degeneration,
glaucoma, corneal disease) that would make assessment of visual status difficult
• Subject is scheduled to undergo cataract surgery
• Subject with any disease, that in the opinion of the ophthalmologist, could
adversely effect the subject’s vision during the course of the study

E.5 End points

E.5.1

Primary end point(s)

Maximum severity of oral mucositis (WHO grades 0/1, 2, 3 or 4)

Cataract specific endpoints:
Incidence of cataract development or progression at month 12, based on an
increase from baseline of ≥ 0.3 in the LOCS III score for any of posterior
subcapsular cataract (P), cortical cataract (C), or nuclear opalescence (NO).

E.5.1.1

Timepoint(s) of evaluation of this end point

Maximum severity of oral mucositis: oral cavity assessments daily from high dose melphalan administration throughout hospitalization. Following hospital discharge 3 x weekly assessments until OM grade ≤1.

Cataract assessments were done at baseline, month 6 and month 12.

E.5.2

Secondary end point(s)

-Incidence of ulcerative oral mucositis (WHO grades 2, 3 or 4)
-Duration of ulcerative oral mucositis (WHO grades 2, 3 and 4)
-Incidence of severe oral mucositis (WHO grades 3 and 4)
-Duration of severe oral mucositis (WHO grades 3 and 4)
-Area under the curve (AUC) for patient-reported MTS

E.5.2.1

Timepoint(s) of evaluation of this end point

Oral cavity assessments daily from high dose melphalan administration throughout hospitalization. Following hospital discharge 3 x weekly assessments until OM grade ≤1.

Patient Reported Outcome questionnaires:

OMDQ: administered at screening and then daily from high-dose Melphalan administration throughout hospitalization. Upon discharge the OMDQ questionnaire administered 3 x weekly until OM grade ≤ 1. The OMDQ also administered at the end of study visit.

EQ-5D: administered at screening and then weekly on approximately day 7, day 14 & day 21, and end of study

FACT-E and MCSQ: administered at screening, end of study, and at day 60-100 & month 6

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

Yes

E.6.13.1

Other scope of the trial description

Health Economics

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

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

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

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

Subjects will undergo an evaluation for the end of study visit at least 30 days after the last administration of investigational product (Day + 32)
All subjects will be followed for disease progression, second primary tumors, additional malignancies and survival until death or for a minimum of 2 years.

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:

239

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2006-12-18.

Yes

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

275

F.4.2.2

In the whole clinical trial

275

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)

According to medical needs.

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

2007-01-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-10-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-02-27

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