E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ACROMEGALY ASSOCIATED WITH PITUITARY GLAND MACROADENOMA |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000599 |
E.1.2 | Term | Acromegaly |
|
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 evaluate the efficacy of Lanreotide Autogel 120 mg when used as primary medical treatment in untreated de novo acromegalic patients with macroadenoma, as assessed by evaluating the change in pituitary tumor volume at Week 48 (after 12 injection – V5) compared to baseline volume (V1). A 20% reduction from baseline (as measured by MRI at V1) will be considered to be clinically significant.
|
|
E.2.2 | Secondary objectives of the trial |
1) To assess the change in tumor volume after 3 injections (V3) and 6 injections (V4) compared to V1, 2) To assess the change in GH, IGF-1 and prolactin levels* at all assessment time-points in comparison to the baseline, , 3) To assess the therapeutic activity of Lanreotide Autogel 120 mg as primary medical treatment on: - Acromegaly symptoms, - Quality of life (using AcroQOL)**, 4) To assess safety based on: - Adverse events, clinical examination, vital signs, - Glucose tolerance, - Standard haematology and biochemistry, - Gallbladder ultrasound. * Prolactin only for patients with initial increased prolactin level (Prolactin > 20 ng/mL). **AcroQOL will only be assessed in countries where a validated translation is available |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-The patient has given written informed consent prior to any study related procedures, -The patient is male or female and is aged between 18 and 75 years, inclusive, -Diagnosis of acromegaly defined by i) GH nadir > 1 ng/mL as assessed by an oral glucose tolerance test for non diabetic patients (central laboratory results) or a mean GH level > 1 ng/mL based on 5 samples taken every 10 to 15 minutes for diabetic patients (GH profile - central laboratory results) AND ii) IGF-1 concentrations elevated above the age- and sex-matched normal range for diabetic and non diabetic patients (central laboratory results), -The patient has a pituitary adenoma with a diameter > or = 10 mm based on Magnetic Resonance Imaging (MRI) central reading, - The patient has no visual field defect identified at the visual evaluation, performed by Goldman Visual Fields Analyser and Automated visual field static perimeter, except visual field abnormality at the time of screening and that is in the investigator’s opinion: •Not related to the pituitary adenoma •Clinically stable condition not presumed to change during the study period •Not modifying the ability to evaluate visual field changes related to the macroadenoma
|
|
E.4 | Principal exclusion criteria |
-The patient has a history of hypersensitivity to Lanreotide or drugs with a similar chemical structure, -The patient has received any unlicensed drug within the 30 days prior to the screening visit or is scheduled to receive an unlicensed drug during the course of the study, -The patient is likely to require treatment during the study with somatostatin analogues other than Lanreotide Autogel 120 mg, dopamine agonist, GH receptor antagonist (pegvisomant), and Cyclosporine, -The patient is a female at risk of pregnancy during the study and is not using acceptable contraceptive method. Females of childbearing potential must provide a negative pregnancy test at start of study and must be using oral, double barrier (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide) or injectable contraception or an intra uterine device. Non childbearing potential is defined as post-menopause for at least 1 year, surgical sterilisation or hysterectomy at least three months before the start of the study, -The patient is pregnant or lactating, -The patient has a history of, or known current, problems with alcohol abuse, -The patient has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude, -The patient has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient’s safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study, -The patient has undergone pituitary surgery or pituitary radiotherapy prior to study entry, -The patient has previously been treated with a somatostatin analogue, -The patient has received a dopamine agonist or a GH receptor antagonist (pegvisomant) prior to study entry, -The patient is expected to require pituitary surgery (adenomectomy) or to receive radiotherapy during the study period, -Patients with suspected associated prolactinoma: prolactin level > 100 ng/mL (central laboratory), -Patient is allergic to Gadolinium (MRI contrast agent) or has acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2), -Patient known by Investigator, to have congenital or acquired optic nerve disease or any visual abnormality with risk of worsening during the course of the study (e.g glaucoma), influencing ability to evaluate Visual Field changes related to the macroadenoma . |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the percentage of patients with significant reduction in tumor volume from baseline MRI (V1) to V5 MRI (W48). A blinded, centrally assessed evaluation of all MRIs will be performed. A 20% reduction from the volume at V1 will be considered to be clinically significant. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | Information not present in EudraCT |
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 |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of the trial is defined as the last visit of the last patient undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |