Extension Study of IONIS-GHR-LRx Administered to Participants With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands

An Open-Label Extension Trial of IONIS GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor Administered Monthly Subcutaneously to Patients With Acromegaly Being Treated With Long-Acting Somatostatin Receptor Ligands (SRL)

The purpose of this study is to assess the safety and efficacy of extended dosing with IONIS GHR-LRx in participants with acromegaly as add-on to somatostatin receptor ligands (SRL) therapy.

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Drug: IONIS GHR-LRx; Drug: Somatostatin Receptor Ligand (SRL)

Detailed Description

This extension study will include participants up to 60 participants with acromegaly from Study NCT03548415. All participants will remain on the same dose from the previous study and receive IONIS GHR-LRx (SC) injection once every 28 days as add-on to SRL therapy for 53 weeks. At the end of 53 weeks, participants will enter a 14-week post-treatment (PT) evaluation period.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1062
    • Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly
• Lithuania
  • Kaunas, Lithuania, LT-50161
    • Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos - Endocrinology clinic
  • Vilnius, Lithuania, 9112
    • Vaidoto Urbanaviciaus Individuali imone - Endokrinologijos klinika
• Poland
  • Kraków, Poland, 31-011
    • Centrum Nowoczesnych Terapii "Dobry Lekarz" Sp. z o. o.
  • Nowa Sól, Poland, 67-100
    • Twoja Przychodnia - Centrum Medyczne Nowa Sol
  • Warsaw, Poland, 03-242
    • Mazowiecki Szpital Bródnowski
• Russian Federation
  • Barnaul, Russian Federation, 656043
    • Multi-field Medical Clinic Anturium LLC
  • Kazan, Russian Federation, 420101
    • Interregional Clinical Diagnostic Center
  • Kemerovo, Russian Federation, 650066
    • Kemerovo Regional Clinical Hospital n.a. S.V. Belyaev
  • Moscow, Russian Federation, 117036
    • Federal State Budget Institution "National Medical Research Center of Endocrinology" of the Ministry of Healthcare of the Russian Federation
  • Moscow, Russian Federation, 119991
    • I.M. Sechenov Moscow First State Medical University
  • Novosibirsk, Russian Federation, 630087
    • Novosibirsk State Regional Clinical Hospital
  • Orenburg, Russian Federation, 460018
    • Orenburg Regional Clinical Hospital
  • Saint Petersburg, Russian Federation, 194156
    • Almazov National Medical Research Centre
  • Tver, Russian Federation, 170036
    • State Budget Healthcare Institution of the Tver Region (Regional Clinical Hospital)
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Nevada
    • Las Vegas, Nevada, United States, 89149
      • 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
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

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:

• Randomized in index trial (CS2) and completed the entire study, or completion of the treatment period for CS2 and completed or plan to complete PTWK5 visit with an acceptable safety profile, per investigator judgment
• Participants with confirmed stable monthly regimen of SRL for 3 months prior to screening
• Able and willing to participate in a 53-week treatment and 14-week post-treatment study

Exclusion Criteria:

• Treatment with any other acromegaly medications taken prior to Day 1 within the time period: bromocriptine: 2 weeks, carbergoline: 4 weeks, quinagolide: 4 weeks, pegvisomant: 4 weeks and pasireotide: 4 months
• Participant who received surgery for pituitary adenoma in the last 3 months prior to screening and participants needing and/or planning to receive surgery for the pituitary adenoma during the trial
• Unwilling to comply with required study procedures during the treatment and post-treatment periods

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: IONIS GHR-LRx + Somatostatin Receptor Ligand (SRL); IONIS GHR-LRx (as per dose in previous study) will be administered subcutaneously once every 28 days for 53 weeks.	Drug: IONIS GHR-LRx; Participants will receive IONIS GHR-LRx by subcutaneous injection.; Drug: Somatostatin Receptor Ligand (SRL); Participants will receive Somatostatin Receptor Ligand (lanreotide, octreotide) once monthly.; Other Names: lanreotide; octreotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Adverse Events	Incidence of adverse events (AEs), serious AEs, treatment related AEs, AEs leading to withdrawal	Up to approximately 16 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baselines in Insulin-like Growth Factor I (IGF-1) Levels	Baseline and at Week 26 and Week 53
Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age-Adjusted Upper Limits	Week 26 and at 28 days after the Week 53 dose
Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age-Adjusted Upper Limits	Week 26 and at 28 days after the Week 53 dose
Percentage of Participants who Begin Other Acromegaly Medication	Up to approximately 16 months
Time From First Dose of IONIS GHR-LRx in this open label extension (CS3) to Date of Initiation of Other Acromegaly Medications	Up to approximately 16 months

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2019
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): July 7, 2022

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 28, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 17, 2023
• Last Verified: March 1, 2023

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; Physiological Effects of Drugs; Antineoplastic Agents; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Octreotide; Lanreotide; Somatostatin
• Other Study ID Numbers: ISIS 766720-CS3; 2019-000591-42 (EudraCT Number)

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