Phase II Study With ITF2984 in Acromegalic Patients

Acromegaly Clinical Trial

— POC  

Official title:

A Randomized, Multicenter, Phase II Study to Investigate Efficacy and Safety of ITF2984 in Acromegalic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02111044
• Other study ID #: DSC/13/2984/05
• Status: Completed
• Phase: Phase 2
• First received: April 8, 2014
• Last updated: June 15, 2016
• Start date: April 2014
• Est. completion date: February 2016

Study information

• Verified date: June 2016
• Source: Italfarmaco
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of MedicinesRomania: National Medicines AgencyPoland: Ministry of HealthNetherlands: Medical Ethics Review Committee (METC)France: Agence Nationale de Sécurité du Médicament et des produits de santéHungary: National Institute for Quality and Organizational Development in Healthcare and MedicinesCzech Republic: State Institute for Drug ControlSerbia: Medicines and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate in acromegalic patients the effect of different doses of ITF2984 on GH and IGF-1 concentrations and to investigate safety and tolerability of three different doses of ITF2984.

Description:

The study will enroll patients with active acromegaly, de novo or partial responder to previous treatment with somatostatin analogues. For patients who had previously received medical therapy for acromegaly a washout periods before study entry of 3 months for long-acting formulation of somatostatin analogs, 2 weeks for octreotide sc, 2 months for pegvisomant and/or cabergoline must be foreseen.

Each patient will be randomized and wll remain in the study for about 6 months, and they will attend a visit every two weeks.

The patients will be treated for 4 months in a total, in particular every month of treatment will be followed by a washout period of 2 weeks.

At each month of treatment the patients will receive one of the four treatment as reported below:

Octreotide 100 mcg sc three times daily (t.i.d) for 4 weeks, ITF2984 500 mcg sc twice a day (b.i.d) for 4 weeks, ITF2984 1000 mcg sc b.i.d for 4 weeks, ITF2984 2000 mcg sc b.i.d for 4 weeks. Patients will be randomized using a 4 way crossover design to receive ITF2984 or octreotide at each treatment month. Each patient will receive all of the four treatments overseen in this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Signed written informed consent.

• Patients with active acromegaly due to a pituitary adenoma. Active acromegaly should be confirmed by 2h five point mean GH level higher than 5 mcg/liter, lack of suppression of GH nadir to less than 1 mcg/liter after oral glucose tolerance test, and elevated IGF-1 for age and sex-matched controls.

• Patients aged between 18 to 80 years old inclusive.

• Patients treated with previous surgery and/or medical therapy or previously untreated (de novo). For patients who had previously received medical therapy for acromegaly a washout periods before study entry of 3 months for long-acting formulation of somatostatin analogs and 2 weeks for octreotide sc must be foreseen. Partial responder means a significant decrease (>50%), without achievement of control of GH and/or IGF-1 levels and/or >20 % tumor shrinkage after at least 6 months of SRL therapy.

• Patients with GH level and IGF-1 level for age and sex-matched controls out of range at baseline (GH at baseline > 2.5mcg/l).

Exclusion Criteria:

• Patients undergone pituitary surgery within the prior 6 months.

• Patients who have received pituitary radiotherapy (within last 10 years).

• Patients with additional active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)

• Patients with compression of the optic chiasm causing any visual field defect.

• Patients who require a surgical intervention for relief of any sign or symptom associated with tumor compression.

• Patients with uncontrolled diabetes defined as having a fasting glucose > 150 mg/dL (8.3 mmol/L) or HbA1c = 8% (Patients can be rescreened after diabetes is brought under adequate control).

• Patients who have had a significant cardiovascular disease in the three months prior to inclusion such as congestive heart failure (NYHA [New York Heart Association] class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, sustained clinically significant bradycardia, advanced heart block, or with a history of acute myocardial infarction.

• A marked baseline prolongation of QT/QTc interval i.e. a mean QT/QTc >450ms after 3 consecutive measurements at least 5 minutes apart.

• Patients with abnormal coaugulation, Prothrombin time (PT), activated partial thromboplastin time (PTT) elevated by 30% above normal limits.

• Symptomatic cholelithiasis, gallstone or chronic liver disease.

• Patients who have a history or presence at the moment of the screening visit of pancreatitis.

• Clinically significant GI, renal or hepatic disease (in the opinion of investigator).

• AST and/or ALT>2ULN.

• Severely reduced renal function (serum creatinine >2.0 mg/dl or 176µmol/L)

• Active HBV and/or active HCV infection.

• Patients who have a history of alcohol or drug abuse in the six-month period prior to the enrollment visit.

• Known hypothyroidism or hypocortisolism not adequately treated with a stable dose of thyroid or steroid hormone replacement therapy for at least the previous 3 months.

• Known hypersensitivity to any of the study medications, or components thereof or a history of drug or other allergy that in the opinion of the Investigator contraindicates their participation.

• Female patients who are pregnant or lactating, and female patient who are of childbearing potential or male patient with female partners of childbearing potential who do not accept the contraception requirements reported in the protocol.

• Patients who have participated in any clinical investigation with an Investigational drug within 3 months before study entry.

• Current or recent (< 2 months) therapy with pegvisomant or cabergoline.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acromegaly

Intervention

Drug:
• Octreotide
octreotide 100 mcg sc t.i.d. for 4 weeks
• ITF2984 500 mcg
ITF2984 500 mcg sc b.i.d for 4 weeks
• ITF2984 1000 mcg
ITF2984 1000 mcg sc b.i.d for 4 weeks
• ITF2984 2000 mcg
ITF2984 2000 mcg sc b.i.d for 4 weeks

Locations

Country	Name	City	State
Czech Republic	St. Anne University Hospital	Brno
Czech Republic	University Hospital Hradec Kralove	Hradec Kralove
France	Université Hôpital Bicêtre	Le Kremlin-Bicêtre
France	Hôpital de la TIMONE	Marseille
Hungary	Az MH Honvédkórház	Budapest
Hungary	Semmelweis University	Budapest
Hungary	University of Pecs	Pecs
Hungary	University of Szeged	Szeged
Italy	Presidio Ospedaliero di Montichiari	Brescia
Italy	Policlinico G. Martino	Messina
Italy	Fondazione Policlinico IRCCS	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Università Federico II	Napoli
Italy	Università di Pisa	Pisa
Italy	San Giovanni Battista Molinette	Torino
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Erasmus Medisch Centrum	Rotterdam
Poland	University Children's Hospital of Cracow	Cracow
Poland	Klinika Endokrynologii Centrum Medycznego Ksztalcenia Podyplomowego	Warsaw
Poland	Samodzielny Publiczny Szpital Kliniczny	Wroclaw
Romania	Institutul de Endocrinologie C.I.Parhon, Sectia clinica de endocrinologie I	Bucharest
Romania	Institutul de Endocrinologie C.I.Parhon, Sectia clinica de endocrinologie II	Bucharest
Romania	Institutul de Endocrinologie C.I.Parhon, Sectia clinica de endocrinologie VI	Bucharest
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical center of Nis	Nis
Spain	Complejo Hospitalario Universitario de Santiago de Compostela	Santiago de Compostela

Sponsors (1)

Lead Sponsor	Collaborator
Italfarmaco

Countries where clinical trial is conducted

Czech Republic,  France,  Hungary,  Italy,  Netherlands,  Poland,  Romania,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effect of treatment on GH and IGF-1	To investigate the effect of treatment on GH and IGF-1 concentrations	4 weeks	No
Secondary	reduction in (random) GH < 1.0 mcg/l and/or normalization of IGF-1	To investigate the biochemical response, defined as a reduction in (random) GH < 1.0 mcg/l and/or normalization of IGF-1.	4 weeks	No
Secondary	reduction of GH to no more than 2.5 mcg/l and/or normalization of IGF-1	To investigate the biochemical response, defined as a reduction of GH to no more than 2.5 mcg/l and/or normalization of IGF-1.	4 weeks	No
Secondary	signs and symptoms of acromegaly	To evaluate variation of signs and symptoms of acromegaly at the end of each month of treatment in comparison with basal status.	4 weeks	Yes
Secondary	PK profile of ITF2984 and Octreotide	To investigate the pharmacokinetic (PK) profile of ITF2984 and Octreotide	4 weeks	No
Secondary	dose-response effect of ITF2984 on GH and IGF1 circulating levels	To compare the effects on GH and IGF1 circulating levels of different doses of ITF2984	4 weeks	No
Secondary	effects of ITF2984 vs Octreotide on GH and IGF1 circulating levels	To compare the effects on GH and IGF1 circulating levels of ITF2984 and Octreotide	4 weeks	No