Clinical Trials Register

Summary
EudraCT Number:	2011-004231-31
Sponsor's Protocol Code Number:	MEC2011pegvqol
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2011-10-19
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

Netherlands - Competent Authority

A.2

EudraCT number

2011-004231-31

A.3

Full title of the trial

Randomized double blind multi-centre study of the effects on low-dose pegvisomant treatment in acromegalic subjects in whom the IGF1 levels has been normalized by long-acting somatostatin analogues

Gerandomiseerd dubbelblind multi center onderzoek naar het effect van de toevoeging van lage dosis pegvisomant in patienten met een normaal IGF1 tijdens de behandeling met een langwerkend somatostatine analoog.

A.3.1

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

the effect of the addition of pegvisomant on quality of life and glucose sensitivity in acromegaly patients

Pegvisomant-toevoeging bij patiënten met acromegalie: effect op symptomen, kwaliteit van leven en insuline-gevoeligheid

A.3.2

Name or abbreviated title of the trial where available

PEQoL

A.4.1

Sponsor's protocol code number

MEC2011pegvqol

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	Erasmus University Medical Centre Rotterdam
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Erasmus University Medical Centre Rotterdam
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Erasmus University Medical Centre Rotterdam
B.5.2	Functional name of contact point	S. neggers MD PhD
B.5.3	Address:
B.5.3.1	Street Address	PO BOX 2040
B.5.3.2	Town/ city	rotterdam
B.5.3.3	Post code	3000 CA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3110703286
B.5.5	Fax number	+3110703363
B.5.6	E-mail	s.neggers@erasmusmc.nl

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	Somavert
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Limited
D.2.1.2	Country which granted the Marketing Authorisation	France
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/3/01/023
D.3 Description of the IMP
D.3.1	Product name	pegvisomant
D.3.2	Product code	PN-800467
D.3.4	Pharmaceutical form	Powder and solvent for cutaneous solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEGVISOMANT
D.3.9.1	CAS number	218620-50-9
D.3.9.4	EV Substance Code	SUB03668MIG
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 and solution for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

acromegaly

acromegalie

E.1.1.1

Medical condition in easily understood language

acromegaly

acromegalie

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

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

To assess the efficacy and safety of the co-administration of low-dose pegvisomant (40 mg, administered via subcutaneous injection given once a week) and long-acting somatostatin analogs (administered once monthly) on the Quality of Life over 16 weeks in 60 acromegalic patients

Om te onderzoeken of 40 mg pegvisomant per week, de kwaliteit van leven kan verbeteren in acromegalie patient met een normaal IGF1 onder somatostatine analoga therapie

E.2.2

Secondary objectives of the trial

To assess the effect of low-dose pegvisomant co-administration on:
 Total body water / body weight.
 Blood pressure
 HbA1c
 BNP levels
 Ring-size
 IGF-I levels
 Safety based on:
• Adverse events, clinical examination, vital signs
• Glucose tolerance
• Standard hematology and biochemistry, including liver function tests

het effect op het metabolisme van lipiden, glucose & insuline vast te stellen. Het effect op lichaamssamenstelling en vitale parameters zoals hart frequentie en bloeddruk.
Daarnaast wordt de veiligheid gecontroleerd op het vlak van leverenzymen, IGF1 en glucose.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Acromegalic patients will be recruited in order to ensure 40 evaluable patients will enter the co-treatment period. All subjects should previously be treated with somatostatin analogues during which treatments their IGF-I levels should have normalized.

Inclusion criteria:
All patients must fulfill the following:
At the screening visit,
• Provision of written informed consent prior to any study related procedures.
• Male or female aged between 18 and 75 years inclusive
• The patient must have had documentation supporting the diagnosis of acromegaly based on elevated GH and/or IGF-1 levels.
• The patient is treated with lanreotide Autogel or octreotide LAR for at least 6 months and has a serum IGF-1 level above the 60th percentile and below ULN, 28 days after the last injection.

Bewezen patiënten met acromegalie, die een IGF1 hebben tussen 60th percentiel en onder bovengrens van normaal. Dit alles onder stabiele somatostatine behandeling voor ≥ 6 maanden.
Leeftijdsgroep 18-75 jaar

E.4

Principal exclusion criteria

Patients will not be included in the study if he/she:
• Has undergone pituitary surgery or radiotherapy within 6 months prior to study entry.
• It is anticipated that the patient will receive pituitary surgery or radiotherapy during the study.
• Has a history of hypersensitivity to lanreotide, octreotide or pegvisomant or drugs with a similar chemical structure.
• Has already been treated with a somatostatin analogue associated with pegvisomant.
• Has received a dopamine agonist within 6 weeks prior to study entry.
• Has been treated with any unlicensed drug within the last 30 days before study entry.
• Has abnormal hepatic function at study entry (defined as AST, ALT, gGT, alkaline phosphatase, or total bilirubin above 2 ULN).
• Is at risk of pregnancy or is lactating. Females of childbearing potential must provide a negative pregnancy test within 5 days before the start of the study and must be using contraception. Non-childbearing potential is defined as post-menopause for at least one year, surgical sterilization or hysterectomy at least three months before the start of the study.
• Has a history of, or known current, problems with alcohol or drug abuse.
• Has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
• Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subject’s safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.
• Renal insufficiency, clearance < 60 ml/min
• Participation in a clinical trail in the last 12 months

E.5 End points

E.5.1

Primary end point(s)

Change in the Quality of Life over 16 weeks. Assessed by AcroQoL and PASQ.

E.5.1.1

Timepoint(s) of evaluation of this end point

At 16 weeks, end of study

E.5.2

Secondary end point(s)

Secondary Efficacy Variables:
 Total body water /body weight.
 Blood pressure
 HbA1c
 BNP levels
 Ring-size
 IGF-I levels
 GH levels
 PEG-levels
 cardiac-sonography
All parameters will be assessed at baseline (V1) plus at 4 (V2), 8 (V3), 12 (V4) and 16 weeks (V6; last visit) after start of co-treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

All parameters will be assessed at baseline (V1) plus at 4 (V2), 8 (V3), 12 (V4) and 16 weeks (V6; last visit) after start of co-treatment.

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)

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

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

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

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

F.3.3.1

Women of childbearing potential not using contraception