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

Phase 3

Completed

• Conditions: Acromegaly
• Interventions: Drug: Lanreotide Autogel®; Drug: Lanreotide Acetate

• Registration Number: NCT02493517
• Lead Sponsor: Ipsen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10
• Study First Submitted: 2015-07-07
• Study First Submitted QC: 2015-07-07
• Study First Posted: 2015-07-09
• Primary Completion: 2016-11
• Study Completion: 2017-02-16
• Results First Submitted: 2018-05-17
• Results First Submitted QC: 2018-05-17
• Results First Posted: 2018-12-14
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-25
• Last Update Posted: 2019-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 128

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lanreotide Autogel® 60mg, 90mg and 120mg	Lanreotide Autogel®	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).
Lanreotide 40mg PR (Lanreotide Acetate for Injection )	Lanreotide Acetate	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.

Primary Outcome Measures

Name	Time	Method
Standardised Mean Change From Baseline in Age-adjusted IGF-1 Levels at the EOST/EW Visit	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 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.

Secondary Outcome Measures

Name	Time	Method
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	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 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.
Median Percentage Change From Baseline in Tumour Volume at the EOST/EW Visit	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 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.
Percentage of Subjects With Normal Age-adjusted IGF-1 Levels at the EOST/EW Visit	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 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.
Percentage of Subjects With GH ≤2.5 Micrograms Per Litre (mcg/L) at the EOST/EW Visit	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 ≤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.
Mean Change From Baseline in GH Values at the EOST/EW Visit	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 mean change from baseline in GH values at the EOST/EW Visit is presented for subjects treated with lanreotide Autogel and lanreotide PR.
Percentage of Subjects With at Least 20% Reduction in Tumour Volume at EOST/EW Visit Compared to Baseline	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 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.
The Percentage of Subjects With GH ≤1 mcg/L at the EOST/EW Visit	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 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.
Percentage of Subjects With at Least One Symptom of Acromegaly at Week 13 and at the EOST/EW Visit Compared to Baseline	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).	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.

Trial Locations

Locations (10)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, China

Fujian Provincial Hospital; 🇨🇳 Fuzhou, China

The First Affiliated Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, China

Affiliate Hospital of Guiyang Medical College; 🇨🇳 Guizhou, China

Jiangsu Provincial People's Hospital; 🇨🇳 Nanjing, China

Huashan Hospital Fudan University; 🇨🇳 Shanghai, China

The Second Hospital of Hebei Medical University; 🇨🇳 Shijiazhuang, China

Tianjin Medical University General Hospital; 🇨🇳 Tianjin, China

Tongji Medical College Huazhong University of Science & Technology; 🇨🇳 Wuhan, China