Study to Assess the Efficacy of an Extended Injection Interval Schedule of Lanreotide Autogel in Acromegalic Subjects (LEAD)

A Prospective, International, Multi-centric, Open-label Study to Assess the Efficacy of an Extended Injection Interval Schedule of Lanreotide Autogel 120 mg in Acromegalic Subjects Who Are Biochemically Controlled on the Long Term Treatment With Octreotide LAR 10 or 20 mg

The purpose of the study is to assess the efficacy of an extended injection interval schedule of lanreotide Autogel 120 mg in acromegalic subjects who are biochemically controlled on long term treatment with octreotide LAR 10 or 20 mg

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Universidade Federal do Rio de Janeiro - Department of Internal Medicine - Section of Endocrinology - Neuroendocrine Research Center
  • Sao Paulo, Brazil
    • Hospital das Clínicas de São Paulo - Internal Medicine - Neuroendocrine Unit - Division of Endocrinology and Metabolism
• Denmark
  • Arhus C, Denmark, DK 8000
    • Arhus University Hospital - Department of Medicinsk AVd M
  • Copenhagen, Denmark, DK-2100
    • Righospitalet - University Department of Endocrinology & Internal Medicine P
  • Odense C, Denmark, DK-5000
    • Odense University Hospital - Department of Endocrinology
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Central Hospital - (HUCH) Division of Endocrinology - Department of Medicine
  • Kuopio, Finland, 70210
    • Kuopio University Hospital - Department of Medicine, Internal Medicine/Endocrinology and Diabetology Division
• France
  • Besançon, France, 25030
    • CHU Besançon - Hôpital Jean Minjoz
  • Bobigny, France, 93009
    • Hôpital Avicenne - Bâtiment Madeleine Breis
  • Bron, France, 69677
    • Hôpital neurologique - Pierre Wertheimer
  • Dijon, France, 21079
    • Hôpital du Bocage Sud - Service d'Endocrinologie
  • La Rochelle, France, 17019
    • CH La Rochelle - Hopital Saint Louis - Service de Médecine interne - Endocrinologie - Maladies Métaboliques- Nutrition
  • Limoges, France, 87042
    • Hôpital Du Cluzeau - Service de Médecine B
  • Nice, France, 06200
    • Hôpital Archet 1 - Service d'Endocrinologie
  • Nîmes, France, 30029
    • CHU de Nîmes - Hôpital Caremeau
  • Paris, France, 75010
    • Hôpital Lariboisière - Service Médecine Interne - Endocrinologie - Nutrition
  • Paris, France, 75013
    • Hopital Pitié-Salpêtrière - Service d'Endocrinologie
  • Paris, France, 75074
    • Hôpital Cochin - Saint-Vincent-de-Paul - La-Roche-Guyon
  • Pessac, France, 33604
    • Hôpital Haut Lévêque - Unité de soins normalisés
  • Reims, France, 51092
    • Hopital Robert Debre
  • Strasbourg, France, 67098
    • Hôpital de Hautepierre, Service de Médecine Interne et Nutrition
  • Tours, France, 37044
    • CHU de Tours - Hopital Bretonneau - Service Endocrinologie-Diabétologie Medecine B
• Greece
  • Athens, Greece
    • Evangelismos Hospital - Department of Endocrinology
  • Athens, Greece
    • Polykliniki Hospital - Department of Endocrinology
  • Piraeus, Greece
    • Metaxa Hospital - Department of Endocrinology
  • Thessaloniki, Greece
    • B IKA Panagia Hospital - Department of Endocrinology
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University hospital, 28 Yongon-dong Chongno-gu
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Severance Hospital - Department of Endocrinology and Metabolism
  • Seoul, Korea, Republic of, 135-710
    • Sungkyunkwan University Samsung Medical Center
• Latvia
  • Riga, Latvia, 1002
    • P. Stradins Clinical University Hospital - Department of Endocrinology
• Netherlands
  • Rotterdam, Netherlands, NL-3015 CE
    • Erasmus Medical Centre - Department of Endocrinology
  • Utrecht, Netherlands, NL-3584 CX
    • UMC Utrecht - Department of Endocrinology, Heidelberglaan 100
• Norway
  • Bergen, Norway, N-5009
    • Department of Medicine, Haukeland Hospital Jonas Lies
• Poland
  • Kielce, Poland, 25-734
    • Swietorkryskie Centrum Onkologii, UL. Artwinskiego 3 - Department of endocrinology and Nuclear Medecine
  • Krakow, Poland, 31501
    • University Hospital in Krakow, Dept. of Endocrinology, Kopernika Str. 17
  • Wroclaw, Poland, 50-367
    • Samodzielny Publiczny Szpital Kliniczny nr 1, Ul. Pasteura 4
• Romania
  • Cluj-Napoca, Romania
    • University of Medicine and Pharmacy Iuliu Hatieganu
• Russian Federation
  • Moscow, Russian Federation
    • Federal State Institution "Endocrinology Research Centre - Federal agency of high-tech medical care" - Neuroendocrinology & Osteopathy Department
  • Moscow, Russian Federation
    • I.M. Sechenov Moscow Medical Academy - Endocrinology Department
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Centre of Serbia - Institute for Endocrinology, Diabetes and Metabolic Diseases, - Dr Subotica Street n°13
  • Novi Sad, Serbia, 21000
    • Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Vojvodina, Hajduk Veljkova 3-9
• Sweden
  • Linkoping, Sweden, 581 85
    • EM-Kliniken, Universitetssjukhuset
  • Lund, Sweden, 221 85
    • Skane University Hospital, Department of Endocrinology
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital, Dpt of Endocrinology, Metabolism & Diabetology, Solna

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The subject has given written informed consent prior to any study-related procedures
• The subject is male or female and is over 18 years of age
• The subject must have had documentation supporting the diagnosis of acromegaly, based on elevated IGF-1 and/or GH levels
• The subject has been receiving octreotide LAR (10 or 20 mg) treatment for at least six months and is biochemically controlled. Control is defined as normal (age and sex adjusted) IGF 1 levels for two consecutive measurements (at least two months apart) preceding study entry
• If the subject is receiving dopamine agonist therapy, treatment should be stable for at least four months, and no change in their dopamine-agonist medication is expected during the entire study period

Exclusion Criteria:

• The subject has received radiation therapy to the pituitary gland before study entry
• The subject has a history of hypersensitivity to lanreotide or drugs with a similar chemical structure
• The subject has received a growth hormone receptor antagonist (pegvisomant) therapy within three months before study entry
• The subject has undergone treatment with any other investigational drug in the 30 days before study entry or is scheduled to receive an investigational drug, other than lanreotide 120 mg, during the course of the study
• The subject has received any unlicensed drug within the 30 days prior to the baseline visit or is scheduled to receive an unlicensed drug during the course of the study

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; 120mg, injections every 6 weeks, then depending on IGF-1 results at Week 24

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Having Maintained Their Injection Interval Schedule of Six Weeks or Increased Their Injection Interval to Eight Weeks Whilst Keeping Their Normalised Insulin Growth Factor (IGF-1) Levels (Age and Sex Adjusted)	A subject was responder if he maintained his injection interval schedule of 6 weeks or increased his injection interval to eight weeks whilst keeping his normalised IGF-1 level (age and sex adjusted) at the end of the study (Week 48)	At week 48 (End of Study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Normalised IGF-1 Levels (Age and Sex Adjusted)	The criterion for a subject is satisfied if he has a normalised IGF-1 level (age and sex adjusted) at week 24.	At week 24
Percentage of Subjects Having Maintained an Injection Interval of Six Weeks or Increasing Their Injection Interval to Eight Weeks	The criterion for a subject is satisfied if he maintained an injection interval of six weeks or increasing his injection interval to eight weeks during Phase 2 of the study.	During phase 2 of the study (up to week 48)
Percentage of Subjects Who Extend Their Injection Interval to Eight Weeks During Phase 2 of the Study, Whilst Maintaining Normalised IGF-1 Levels	The criterion for a subject is satisfied if he extended his injection interval to eight weeks during Phase 2 of the study, whilst maintaining normalised IGF-1 levels at Week 48.	At week 48
Mean Change From Baseline in IGF-1 Values [Expressed as % of Upper Limit of Normal (ULN)], Overall and by Injection Interval	IGF-1 change from Baseline to Week 48 = Mean IGF-1 level at Week 48 - Mean IGF-1 level at Baseline	Baseline (visit 1) and week 48
Treatment Group (A, B or C) Mean Baseline IGF-1 Levels (Expressed as % of ULN) in Subjects Who Maintained Normalised IGF-1 Values at Week 48. Comparisons Will be Made as Follows: A Versus B, A Versus C, A Versus (B+C) and B Versus C		Baseline (visit 1)
Mean Baseline IGF-1 Levels (Expressed as % of ULN) in All Groups (A, B and C) Versus Mean Baseline IGF-1 Levels (Expressed as % of ULN) in Subjects With Uncontrolled IGF-1 Levels at Week 24		Baseline (visit 1)
Symptoms of Acromegaly (Headache, Excessive Perspiration, Fatigue, Soft Tissue Swelling and Arthralgia)	Acromegaly symptoms were assessed by the patients using the Patient Assessed Acromegaly Symptom Questionnaire (PASQ) scale ranging from 0 (No symptoms) to 8 (Severe, incapacitating symptoms).	At baseline, week 24 and week 48
Mean Changes From Baseline in Quality of Life Scores (AcroQoL)	AcroQoL score groups 22 components: Eight physical, Seven psychological appearance and Seven psychological personal relations, adjusted to a scale of 100, where a score of 100 corresponds to the best possible QoL and 0 to the worst.	At weeks 24 and 48
Mean Changes From Baseline in Quality of Life Scores (SF-36)	Short Form-36 questionnaire (SF-36) score comprises eight components: Physical function, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health on a scale of 100, where a score of 100 corresponds to the best possible QoL and 0 to the worst.	At weeks 24 and 48
Percentage of Subjects With Normalized IGF-1 Levels (Age and Sex Adjusted), Without Any Worsening of the AcroQoL Change Score Between Inclusion and Week 48	The criterion for a subject is satisfied if he had a IGF-1 level (age and sex adjusted) without any worsening of the AcroQoL change score between Inclusion and Week 48.	At week 48 (End of Study)
Correlation Between the Changes From Baseline in Quality of Life (AcroQoL) With the Corresponding Changes in IGF-1 Level (Expressed as % of ULN) at Each Visit	AcroQoL change from Baseline to Week 24 (48) = AcroQoL at Week 24 (48) - AcroQoL at Baseline. IGF-1 change from Baseline to Week 24 (48) = IGF-1 at Week 24 (48) - IGF-1 at Baseline. Correlation presented is a Spearman correlation (non parametric).	At weeks 24 and 48
Serum Growth Hormone (GH) Levels		At Baseline, week 24 and week 48
Percentage of Subjects With GH Level Less Than or Equal to 2.5 ng/mL		At weeks 24 and 48
Subject Treatment Schedule Preference	At week 24, the preference assessed between Octreotide Long Acting Repeatable intramuscular injection (Oct-LAR IM) every 4 weeks and Lanreotide Autogel 120 mg subcutaneous injection (SC) every 6 weeks. At week 48, the preference is assessed between Oct-LAR IM every 4 weeks and Lanreotide Autogel 120 mg SC either injected every 4, 6 or 8 weeks (as injected during Phase II of the study).	At weeks 24 and 48

Collaborators and Investigators

• Sponsor: Ipsen

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: June 18, 2008
• First Submitted That Met QC Criteria: June 18, 2008
• First Posted (Estimate): June 19, 2008

Study Record Updates

• Last Update Posted (Actual): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 10, 2019
• Last Verified: January 1, 2019

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: A-38-52030-214; 2007-005838-37 (EudraCT Number)