Lanreotide as Primary Treatment for Acromegalic Patients With Pituitary Gland Macroadenoma

Study Overview
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Brief Summary
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Acromegaly is a chronic disease caused by excessive secretion of growth hormone (GH) and mainly due to benign tumour localized in the pituitary gland. The disease develops insidiously, causing a gradual progression of symptoms; consequently most patients are diagnosed in their fourth decade of life. Administration of somatostatin analogues such as lanreotide have been shown to result in normalisation or the decrease of GH and insulin growth factor (IGF-1) levels and improvement of clinical symptoms in acromegalic patients. The purpose of this study is to evaluate whether lanreotide is also effective on tumour volume reduction (tumour shrinkage) and the benefits of this potential tumour shrinkage on disease symptoms and patient's quality of life.

Official Title
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Phase IIIb, Multicentre, Open-label, Single-arm, Study to Assess the Efficacy and Safety of Lanreotide Autogel 120 mg Administered Every 28 Days as Primary Medical Treatment in Acromegalic Patients With Macroadenoma

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: Lanreotide autogel 120 mg


Participation Criteria
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Eligibility Criteria
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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 ( 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 greater than or equal to 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 Clinical judgement: 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 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 or drugs that are not permitted by the study protocol, The patient is a female at risk of pregnancy during the study and is not using acceptable contraceptive methods. 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), 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 jeopardize 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 results), 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lanreotide autogel 120 mg<br> | Drug: Lanreotide autogel 120 mg<br>* 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Relevant Reduction in Pituitary Tumour Volume (as Measured by MRI) From Baseline Volume (Visit 1) to Week 48 (After 12 Injections at Visit 5) | A blinded, centrally assessed evaluation of all MRIs was performed. A 20% reduction from the volume at Visit 1 was considered to be clinically relevant. | Week 1 and Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With at Least a 20% Reduction in Tumour Volume From Baseline Volume (Visit 1) to Week 12 (Visit 3) and Week 24 (Visit 4). |  | Baseline (week 1) to week 12 and week 24 | 
| Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of IGF-1 Levels |  | Week 12, 24, and 48 | 
| Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Serum GH Levels. |  | Week 12, 24, and 48 | 
| Change From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Prolactin Levels |  | Week 12, 24 and 48 | 
| Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Arthralgia) From Baseline | The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged. | Week 12, 24 and 48 | 
| Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Excessive Perspiration) From Baseline | The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged. | Week 12, 24 and 48 | 
| Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Fatigue) From Baseline | The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged. | Week 12, 24 and 48 | 
| Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Headache) From Baseline | The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged. | Week 12, 24 and 48 | 
| Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Soft Tissue Swelling) From Baseline | The status of clinical signs of acromegaly assessed by an acromegaly symptoms questionnaire (paper form) completed by the patient at each study visit. The scoring for each clinical sign of acromegaly on the questionnaire is from 0 (no symptom) to 8 (severe, incapacitating symptom). The variation (or no variation) in scores indicate whether the clinical sign of acromegaly had improved, worsened or was unchanged. | Week 12, 24 and 48 | 
| Changes in the Global Acromegaly Quality of Life Assessment (AcroQoL) From Baseline | Acromegaly Quality of Life Assessment (AcroQoL) questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life. | Week 12, 24 and 48 |