Lanreotide Autogel and Pegvisomant Combination Therapy in Acromegalic Patients

Condition(s) targeted: Acromegaly

Intervention: lanreotide (Autogel formulation) (Drug); Pegvisomant (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Ipsen

Official(s) and/or principal investigator(s):
Catherine Lesage, MD, Study Director, Affiliation: Ipsen

The main aim of this study is to assess the efficacy of the co-administration of lanreotide Autogel 120 mg (administered via deep sub-cutaneous injections every 28 days) and pegvisomant (administered at 40 to 120 mg per week via sub-cutaneous injection given once or twice a week) on IGF-1 levels over 28 weeks in acromegalic patients. The primary endpoint will be the percentage of acromegalic patients with normalised (age and sex adjusted) IGF-1 level at the end of the co-treatment period.

Official title: Phase III, Multicentre, Open Study to Assess the Efficacy and Safety Profiles of the co-Administration of Lanreotide Autogel 120 mg (Administered Via Deep Subcutaneous Injections Every 28 Days) and Pegvisomant 40 to 120 mg Per Week (Administered Via Subcutaneous Route Once or Twice a Week) in Acromegalic Patients Failing to Respond to Lanreotide Autogel 120 mg Alone

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Primary outcome: The percentage of acromegalic patients with normalised (age and sex adjusted) IGF-1 level at the end of the co-treatment period.

Secondary outcome:

Acromegaly symptoms

Quality of life

Adverse events, clinical evaluation, vital signs

Glucose tolerance

Standard haematology and biochemistry

Gallbladder ultrasound

Pituitary tumor size

ECG

Anti-lanreotide Autogel antibodies, anti-pegvisomant antibodies

Lanreotide and pegvisomant serum levels (minimum observed concentrations Cmin)

To assess the effect of lanreotide - pegvisomant co-administration on: GH, GH binding protein, acid labile subunit and prolactin levels

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- The patient must have had documentation supporting the diagnosis of acromegaly,

including elevated GH and/or IGF-1 levels

- The patient is treated with pegvisomant, because of IGF-1 level remaining above ULN

when treated with somatostatin analogue, on a daily basis for at least 3 months and has normal (age and sex adjusted) IGF-1 level, or IGF-1 level above the upper limit of normal (ULN) after treatment with pegvisomant 30 mg per day, OR the patient is treated with lanreotide Autogel or octreotide LAR for at least 6 months including 3 months at the highest marketed dose and has a serum IGF-1 level above ULN, 28 days after the last injection

- At the end of the run-in period, The patient has a serum IGF-1 level above 1. 2 x ULN,

or a serum IGF-1 level between ULN and 1. 2 x ULN and a serum GH nadir > 1 µg/L (assessed by an OGTT), 28 days after the 3rd injection of lanreotide Autogel 120 mg OR the patient is diabetic and has a serum IGF-1 level above 1. 2 ULN, 28 days after the 3rd injection of lanreotide Autogel 120 mg

Exclusion Criteria:

- The patient has undergone pituitary surgery or radiotherapy within 6 months prior to

study entry, or it is anticipated that it will be done during the study

- The patient has already been treated with a somatostatin analogue associated with a GH

antagonist

- The patient has received dopamine agonist within 6 weeks prior to the study entry

- The patient has abnormal hepatic function at study entry (defined as AST, ALT, GGT,

alkaline phosphatase, prothrombin time or total bilirubin above 2 ULN)

- The patient is at risk of pregnancy or is lactating

Charles University, Prague 120 00 PRAHA 2, Czech Republic

University Hospital, Charles University, Hradec Kralove 500 05, Czech Republic

Aarhus Kommunehospital, Aarhus, Denmark

Hôpital Bicêtre, Le Kremlin-Bicêtre 94275, France

CHU de Rangueil, Toulouse 31054, France

Clinique Marc Linquette, Lille Cedex 59037, France

Hôpital de la Timone, Marseille Cedex 13385, France

Groupe Hospitalier Henri Mondor- Albert Chenevier, Créteil Cedex, France

Charite Campus Mitte, Berlin 10117, Germany

Medizinische Klinik Innenstadt, Munchen 80336, Germany

Klinikum Johann Wolfgang Goethe-Universität, Frankfurt 605090, Germany

Anticancer Hospital Metaxa Piraeus, Piraeus 18537, Greece

Universitá di Torino, Torino 10126, Italy

Universitá degli Studi di Milano, Milano 20122, Italy

University Federico II, Napoli 80131, Italy

Dept. of Internal Medicine Erasmus MC, Rotterdam 3015 GD, Netherlands

Leiden University Medical Center, Leiden 2300 RC, Netherlands

Hospital General de Alicante, Alicante 03012, Spain

Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela 15706, Spain

Clínica Puerta de Hierro, Madrid 28035, Spain

Sahlgrenska University Hospital, Göteborg 413 45, Sweden

Uppsala University Hospital, Uppsala 75185, Sweden

Christie Hospital and Holt Radium Institute, Manchester M20 4BX, United Kingdom

Royal Hallamshire Hospital, Sheffield, United Kingdom

Starting date: October 2006
Last updated: June 18, 2008