A Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx Administered in Patients With Acromegaly

An Open Label, Randomized, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor, Administered Monthly as Monotherapy in Patients With Acromegaly

The purpose of this study was to determine the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy in patients with acromegaly.

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Drug: GHR-LRX

Detailed Description

This was a multi-center, open-label, randomized, Phase 2 study of IONIS-GHR-LRx in up to 40 participants with acromegaly. Participants were randomized to 1 of 2 treatment groups to receive IONIS GHR-LRx monthly for 73 weeks. At the end of 73 weeks, participants entered a 14-week post-treatment (PT) evaluation period.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia, 10138
    • East-Tallinn Central Hospital
  • Tartu, Estonia, 50406
    • Tartu University Hospital
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
• Italy
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
• Latvia
  • Rīga, Latvia, LV-1002
    • Pauls Stradins Clinical University hospital
• Lithuania
  • Alytus, Lithuania, 63246
    • Vaidoto Urbanaviciaus Individuali imone
  • Kaunas, Lithuania, 50161
    • Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos
• Poland
  • Warszawa, Poland, 03-242
    • Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny, im. Jana Mikulicza-Radeckiego we Wroclawiu,
  • Wrocław, Poland, 51-162
    • Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.
• Romania
  • Bucharest, Romania, 060044
    • Centrul Medical Unirea Bucuresti, Endocrinologie
• Russian Federation
  • Moscow, Russian Federation, 119146
    • I.M. Sechenov Moscow First State Medical University
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Novi Sad, Serbia, 21000
    • Clinical Center of Vojvodina
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center Inc.
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43201
      • Endocrinology Associates, Inc
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males or females with a documented diagnosis of Acromegaly* who are 18 to 75 years old (inclusive) at the time of informed consent.

2. Have had pituitary surgery (e.g. transsphenoidal) unless there was a contraindication to surgery and are either acromegaly medical treatment naïve, or who had not taken any other acromegaly medications prior to the screening visit as outlined below

   • bromocriptine: 2 weeks
   • cabergoline: 4 weeks
   • quinagolide: 4 weeks
   • octreotide daily injection (SC) or oral formulation: 4 weeks
   • pegvisomant: 4 weeks
   • octreotide LAR: 3 months
   • pasireotide LAR: 4 months
   • lanreotide (all formulations): 3 months
3. At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × ULN, inclusive, adjusted for age and sex.
4. Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, abstinent, or using 1 highly effective method of birth control

Exclusion Criteria:

1. Participants who received surgery for pituitary adenoma within the last 3 months before the trial, and/or planning to receive surgery during the trial
2. Participants who received radiotherapy for pituitary adenoma within the last 2 years before the trial, and/or planning to receive radiotherapy during the trial
3. Participants with a pituitary tumor that, per Investigator judgment, is worsening (e.g., either growing or at risk of compressing or abutting the optic chiasm or other vital structures) as assessed by pituitary/sellar MRI protocol at Screening or within 3 months of Screening. CT scan is allowed if MRI is contraindicated
4. Evidence of decompensated cardiac function per medical judgement and/or New York Heart Association (NYHA) Class 3 or 4
5. Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment
6. Symptomatic cholelithiasis, and/or choledocholithiasis

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: GHR-LRX 120 mg; Participants received GHR-LRX 120 mg subcutaneous (SC) injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).	Drug: GHR-LRX; GHR-LRX was administered by SC injection.; Other Names: ISIS 766720
Experimental: GHR-LRX 160 mg; Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).	Drug: GHR-LRX; GHR-LRX was administered by SC injection.; Other Names: ISIS 766720

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27	IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Baseline of IGF-1 is defined as the average value of Screening and Day 1. A negative percent change from Baseline indicated improvement.	Baseline to Week 27

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27)	Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's upper limit of normal (ULN).	At Week 27
Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27)	Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's ULN.	At Week 27
Change From Baseline in Serum IGF-1 Over Time	IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative change from baseline indicated improvement.	Up to approximately 80 weeks
Percent Change From Baseline in Serum IGF-1 Over Time	IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative percent change from Baseline indicated improvement.	Baseline, Week 3, 5, 7, 9, 11, 13, 15, 17, 21, 25, 27, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Actual): July 15, 2022
• Study Completion (Actual): May 4, 2023

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): October 3, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: acromegaly; IONIS-GHR-LRx
• 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
• Other Study ID Numbers: ISIS 766720-CS5; 2020-000675-20 (EudraCT Number); NCT04522180 (Other Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No