Lanreotide as Primary Treatment for Acromegalic Patients With Pituitary Gland Macroadenoma (PRIMARYS)

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

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.

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Drug: Lanreotide autogel 120 mg

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, B2650
    • University Hospital Antwerpen
• Czechia
  • Praha, Czechia, 128 08 Praha 2
    • Všeobecná fakultní nemocnice, Karlova Univerzita
• Finland
  • Helsinki, Finland, 9 FIN-00290
    • Helsinki University Center Hospital
  • Turku, Finland, 20520
    • The Turku University Central Hospital
• France
  • Bois-Guillaume, France, 76230 Cedex
    • Hôpital de Bois Guillaume
  • Créteil, France, 94010
    • Chu Henri Mondor
  • Grenoble, France, 38043 Cedex
    • CHU Grenoble Albert Michallon
  • Lille, France
    • CHRU Lille Hôpital Claude Huriez
  • Lyon, France, 69677 Bron Cedex
    • Groupement Hospitalier Est
  • Marseille, France, 13385
    • Hôpital de la Timone
  • Paris, France, 94275 Cedex
    • Hopital Bicetre
  • Pessac, France, 33604 Cedex
    • Hôpital Haut Levêque
  • Reims, France
    • CHU de Reims, Hôpital Robert Debré
• Germany
  • Erlangen, Germany, 91054
    • Friedrich-Alexander University
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe-Universität
  • Hamburg, Germany, 20357
    • ENDOC Zentrum für Endokrine Tumoren und Praxis für Endokrinologie, Andrologie und medikamentöse Tumortherapie
  • München, Germany, 80336
    • Medizinische Klinik Innenstadt
• Italy
  • Messina, Italy, 98125
    • AOU Policlinico "G. Martino" Messina
  • Napoli, Italy, 5 80131
    • Università Federico II di Napoli, Dipartimento di Endocrinologia Molecolare e Clinicae Oncologia
  • Roma, Italy, 00168
    • Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, U.O.C. di Endocrinologia
• Netherlands
  • Rotterdam, Netherlands, 3000
    • Erasmus MC Rotterdam
  • Utrecht, Netherlands, 3508
    • UMC Utrecht
• Turkey
  • Istanbul, Turkey, 34303
    • Cerrahpasa Medical Facility
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • 27/28 Aberdeen Royal Infirmary
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lanreotide autogel 120 mg	Drug: Lanreotide autogel 120 mg; 12 months

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ipsen

Publications and helpful links

General Publications

• Caron PJ, Bevan JS, Petersenn S, Flanagan D, Tabarin A, Prevost G, Maisonobe P, Clermont A; PRIMARYS Investigators. Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab. 2014 Apr;99(4):1282-90. doi: 10.1210/jc.2013-3318. Epub 2013 Jan 1.
• Caron PJ, Bevan JS, Petersenn S, Houchard A, Sert C, Webb SM; PRIMARYS Investigators Group. Effects of lanreotide Autogel primary therapy on symptoms and quality-of-life in acromegaly: data from the PRIMARYS study. Pituitary. 2016 Apr;19(2):149-57. doi: 10.1007/s11102-015-0693-y.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: June 3, 2008
• First Submitted That Met QC Criteria: June 3, 2008
• First Posted (Estimate): June 5, 2008

Study Record Updates

• Last Update Posted (Actual): October 14, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Acromegaly; Antineoplastic Agents; Lanreotide
• Other Study ID Numbers: 2-79-52030-207; 2007-000155-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).