Efficacy and Safety of Lanreotide Autogel® 60, 90 or 120 mg With Lanreotide 40 mg Prolonged Release (PR) in Acromegaly (LANTERN)

A Phase III, Prospective, Randomised, Open Label Study to Compare the Efficacy and Safety of Lanreotide Autogel® 60, 90 or 120 mg With Lanreotide 40 mg PR in Subjects With Active Acromegaly

The purpose is to compare the efficacy and safety of lanreotide autogel® 60mg, 90mg or 120mg with lanreotide 40mg PR in subjects with active acromegaly.

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Drug: Lanreotide Autogel®; Drug: Lanreotide Acetate

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Fuzhou, China, 350004
    • Fujian Provincial Hospital
  • Guangzhou, China, 510080
    • The First Affiliated Hospital, Sun Yat-sen University
  • Guizhou, China, 550004
    • Affiliate Hospital of Guiyang Medical College
  • Nanjing, China, 210029
    • Jiangsu Provincial People's Hospital
  • Shanghai, China, 200040
    • Huashan Hospital Fudan University
  • Shijiazhuang, China, 050000
    • The Second Hospital of Hebei Medical University
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Wuhan, China, 430030
    • Tongji Medical College Huazhong University of Science & Technology

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:

• Subject has active acromegaly defined as elevated GH and IGF-1 levels (measured at a central laboratory) as outlined below:

  • A serum level for IGF-1 ≥1.3 x upper limit of normal range (ULN) during the screening period (applicable to both treatment naïve subjects and subjects who have stopped treatment and undergone a washout period prior to Visit 1(Week -4).
  • Subjects must have mean serum GH concentration ≥2.5 μg/L in a GH cycle (5 samples taken at 0, 30, 60, 90 and 120 minutes) during the screening period.
• The subject has undergone surgical removal of an adenoma for acromegaly at least 3 months prior to Screening, or is likely to require pituitary surgery in the future but not before completing at least 32 weeks of study treatment plus an additional follow up of 8 weeks for subjects taking part in the pharmacokinetics (PK) extension, or for whom pituitary surgery is not an option (due to contraindications, refusal etc.) and is therefore never likely to undergo pituitary surgery.

Exclusion Criteria:

• The subject has been treated with radiotherapy within 10 years prior to Screening.
• The subject has been treated with lanreotide Autogel, lanreotide PR, pegvisomant, cabergoline or octreotide LAR within 3 months of Screening or octreotide immediate release (IR) or bromocriptin within 2 weeks of Screening.
• The subject has a history of or currently presents with clinically significant ventricular or atrial dysrhythmias ≥Grade 2, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
• The subject has uncontrolled diabetes (glycosylated haemoglobin (HbA1c) >8.5%).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lanreotide Autogel® 60mg, 90mg and 120mg; Lanreotide Autogel 90mg from day 1 to week 13, 1 injection every 4 weeks (4 in total), titrated to 60mg, 90mg, or 120mg at week 17, then from week 17 to week 29 each group receives 1 injection every 4 weeks (4 in total/group).	Drug: Lanreotide Autogel®; Lanreotide Autogel 60mg, 90mg, and 120mg, pre-filled syringe, deep subcutaneous injection (provided as a supersaturated solution of lanreotide acetate).
Active Comparator: Lanreotide 40mg PR (Lanreotide Acetate for Injection ); Lanreotide PR 40mg from day 1 to week 15, 1 injection every 10 days, then at dose titration (week 16) injection frequency will either remain at 10 days or increase to 14 days or decrease to 7 days up until week 30 or 31.	Drug: Lanreotide Acetate; Lanreotide PR 40mg white freeze-drying cake, 40mg/vial, deep subcutaneous injection (provided as a sterile injectable lyophilisate of lanreotide acetate).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standardised Mean Change From Baseline in Age-adjusted IGF-1 Levels at the EOST/EW Visit	The standardised mean change from Baseline in age-adjusted log-transformed IGF-1 standard deviation score (SDS) at EOST/EW is presented for subjects treated with both lanreotide Autogel and lanreotide PR. Back-transformed results are presented in addition to the results without back-transformation. For each subject the IGF-1 SDS value was calculated based on the z-score derivation: IGF-1 SDS = (IGF-1 - mean)/ standard deviation (SD), with mean and SD derived from the upper limit of normal (ULN) and lower limit of normal (LLN) margins for each age category. ULN = Mean + 2 SD; LLN = Mean - 2 SD. The SDS indicates the number of standard deviations away from the mean. A SDS of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A negative change in the SDS indicates a decrease in the mean age-adjusted IGF-1 values.	Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Normal Age-adjusted IGF-1 Levels at the EOST/EW Visit	The percentage of subjects with normal age-adjusted IGF-1 levels at the EOST/EW Visit is presented for subjects treated with Lanreotide Autogel and Lanreotide PR. At baseline, all subjects had abnormal IGF-1 levels as per protocol entry criteria.	Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).
Percentage of Subjects With GH ≤2.5 Micrograms Per Litre (mcg/L) at the EOST/EW Visit	The percentage of subjects with GH ≤2.5 mcg/L at the EOST/EW Visit is presented for subjects treated with lanreotide Autogel and lanreotide PR. At baseline, all subjects had GH levels >2.5 mcg/L as per protocol entry criteria.	Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).
The Percentage of Subjects With GH ≤1 mcg/L at the EOST/EW Visit	The percentage of subjects with GH ≤1 mcg/L at the EOST/EW Visit is presented for subjects treated with lanreotide Autogel and lanreotide PR. At baseline, all subjects had GH levels >2.5 mcg/L as per protocol entry criteria.	Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).
Percentage of Subjects With Normal Age-adjusted IGF-1 Levels and Who Have GH Levels >1 mcg/L and ≤2.5 mcg/L at the EOST/EW Visit	The percentage of subjects with normal age-adjusted IGF-1 levels and who have GH levels >1 mcg/L but ≤2.5 mcg/L at the EOST/EW Visit is presented for subjects treated with lanreotide Autogel and lanreotide PR. The calculation of percentages was based on the overall ITT population. At baseline, all subjects had abnormal IGF-1 levels and GH levels >2.5 mcg/L as per protocol entry criteria.	Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).
Mean Change From Baseline in GH Values at the EOST/EW Visit	The mean change from baseline in GH values at the EOST/EW Visit is presented for subjects treated with lanreotide Autogel and lanreotide PR.	Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).
Percentage of Subjects With at Least 20% Reduction in Tumour Volume at EOST/EW Visit Compared to Baseline	The percentage of subjects with at least a 20% reduction in the solid component of the tumour volume at the EOST/EW Visit compared to baseline is presented for the subgroup of subjects who had solid tumours at baseline. The tumour volume was measured by Magnetic Resonance Imaging (MRI) at Screening and at the EOST/EW Visit, and then assessed by two independent blinded readers.	Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).
Median Percentage Change From Baseline in Tumour Volume at the EOST/EW Visit	The median percentage change in the solid component of the tumour volume from baseline to the EOST/EW Visit is presented. The tumour volume was measured by MRI at Screening and at the EOST/EW Visit, and then assessed by two independent blinded readers.	Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).
Percentage of Subjects With at Least One Symptom of Acromegaly at Week 13 and at the EOST/EW Visit Compared to Baseline	The percentage of subjects with at least one symptom of acromegaly at Week 13 and at the EOST/EW Visit compared with baseline is presented for subjects treated with lanreotide Autogel and lanreotide PR. The symptoms of acromegaly monitored included: headache, excessive perspiration, fatigue, soft tissue swelling and arthralgia.	Baseline, Week 13 Visit and EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group).

Collaborators and Investigators

• Sponsor: Ipsen

Publications and helpful links

General Publications

• An Z, Lei T, Duan L, Hu P, Gou Z, Zhang L, Durand-Gasselin L, Wang N, Wang Y, Gu F; LANTERN study investigators. Efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release in Chinese patients with active acromegaly: results from a phase 3, prospective, randomized, and open-label study (LANTERN). BMC Endocr Disord. 2020 May 4;20(1):57. doi: 10.1186/s12902-020-0524-7.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): February 16, 2017

Study Registration Dates

• First Submitted: July 7, 2015
• First Submitted That Met QC Criteria: July 7, 2015
• First Posted (Estimate): July 9, 2015

Study Record Updates

• Last Update Posted (Actual): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 25, 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; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Lanreotide; Somatostatin
• Other Study ID Numbers: 8-55-52030-289; CTR20140698 (Other Identifier: www.ChinaDrugTrials.org.cn)