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

• ClinicalTrials.gov Identifier: NCT00690898
• Recruitment Status: Completed
• First Posted: June 5, 2008
• Results First Posted: December 23, 2013
• Last Update Posted: October 14, 2022
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Tracking Information

• First Submitted Date: June 3, 2008
• First Posted Date: June 5, 2008
• Results First Submitted Date: November 4, 2013
• Results First Posted Date: December 23, 2013
• Last Update Posted Date: October 14, 2022
• Study Start Date: May 2008
• Actual Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 4, 2013)

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) [ Time Frame: Week 1 and Week 48 ]

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.

• Original Primary Outcome Measures (submitted: June 3, 2008): The primary efficacy endpoint will be the percentage of patients achieving reduction in tumor volume at V5 (at Week 48) in comparison to baseline (as measured by MRI) [ Time Frame: From W1 (baseline) to W48. ]

Current Secondary Outcome Measures (submitted: January 8, 2014)

• 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). [ Time Frame: 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 [ Time Frame: Week 12, 24, and 48 ]
• Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Serum GH Levels. [ Time Frame: Week 12, 24, and 48 ]
• Change From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Prolactin Levels [ Time Frame: Week 12, 24 and 48 ]
• Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Arthralgia) From Baseline [ Time Frame: Week 12, 24 and 48 ]
  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.
• Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Excessive Perspiration) From Baseline [ Time Frame: Week 12, 24 and 48 ]
  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.
• Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Fatigue) From Baseline [ Time Frame: Week 12, 24 and 48 ]
  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.
• Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Headache) From Baseline [ Time Frame: Week 12, 24 and 48 ]
  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.
• Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Soft Tissue Swelling) From Baseline [ Time Frame: Week 12, 24 and 48 ]
  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.
• Changes in the Global Acromegaly Quality of Life Assessment (AcroQoL) From Baseline [ Time Frame: Week 12, 24 and 48 ]
  Acromegaly Quality of Life Assessment (AcroQoL) questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life.

Original Secondary Outcome Measures (submitted: June 3, 2008)

• Change of serum IGF-1 level and serum GH levels [ Time Frame: At W1, 12, 24 & 48 ]
• Changes of prolactin level in patients with initially increased prolactin level (at screening) [ Time Frame: At each assessment (W12, 24 & 48). ]
• Change of clinical signs of acromegaly [ Time Frame: At each assessment visit at W12,24 &48 ]
• Changes in the quality of life assessment [ Time Frame: At each assessment visit at W12, 24 & 48 ]
• Adverse events and local tolerability information [ Time Frame: Recorded at any time during the study ]
• Vital signs [ Time Frame: Recorded at each assessment ]
• Physical examination findings [ Time Frame: Recorded at each assessment ]
• Gallbladder ultrasound [ Time Frame: Assessed at screening and W48 ]
• Laboratory tests: standard haematology and biochemistry analyses [ Time Frame: At W1 and W48 ]
• Glucose tolerance based on fasting blood glucose [ Time Frame: At W12, 24 & 48 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lanreotide as Primary Treatment for Acromegalic Patients With Pituitary Gland Macroadenoma
• Official Title: 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acromegaly

Intervention

Drug: Lanreotide autogel 120 mg

12 months

Study Arms

Experimental: Lanreotide autogel 120 mg

Intervention: Drug: Lanreotide autogel 120 mg

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 29, 2011): 108
• Original Estimated Enrollment (submitted: June 3, 2008): 100
• Actual Study Completion Date: February 2012
• Actual Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, Finland, France, Germany, Italy, Netherlands, Turkey, United Kingdom
• Removed Location Countries: Czech Republic, Spain, Sweden

Administrative Information

• NCT Number: NCT00690898
• Other Study ID Numbers: 2-79-52030-207; 2007-000155-34 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

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.

• 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.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
• URL: https://vivli.org/members/ourmembers/

• Current Responsible Party: Ipsen
• Original Responsible Party: Antoine Clermont, Ipsen
• Current Study Sponsor: Ipsen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ipsen Medical Director; Ipsen

• PRS Account: Ipsen
• Verification Date: September 2022