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

June 4, 2023 updated by: Ionis Pharmaceuticals, Inc.

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 is 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

Intervention / Treatment

Detailed Description

This is a multi-center, open-label, randomized, Phase 2 study of IONIS-GHR-LRx in up to 40 participants with acromegaly. Participants will be randomized to 1 of 3 treatment groups to receive a single dose of IONIS GHR-LRx monthly for 73 weeks. At the end of 73 weeks, participants will enter a 14-week post-treatment (PT) evaluation period.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IONIS-GHR-LRx Dose 1
Single dose of IONIS-GHR-LRx Dose 1 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Drug: IONIS-GHR-LRx
IONIS-GHR-LRx will be administered by SC injection.
Experimental: IONIS-GHR-LRx Dose 2
Single dose of IONIS-GHR-LRx Dose 2 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Drug: IONIS-GHR-LRx
IONIS-GHR-LRx will be administered by SC injection.
Experimental: IONIS-GHR-LRx Dose 3
Single dose of IONIS-GHR-LRx Dose 3 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Drug: IONIS-GHR-LRx
IONIS-GHR-LRx will be administered by SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percent Change From Baseline in Insulin-like Growth Factor I (IGF-1) to Week 27
Time Frame: Up to Week 27
Up to Week 27

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at Day 183 (Week 27)
Time Frame: At Week 27
At Week 27
Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at Day 183 (Week 27)
Time Frame: At Week 27
At Week 27
Change From Baseline in Serum IGF-1 Over Time
Time Frame: Up to approximately 80 weeks
Up to approximately 80 weeks
Percent Change From Baseline in Serum IGF-1 Over Time
Time Frame: Up to approximately 80 weeks
Up to approximately 80 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ionis Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

June 6, 2023

Last Update Submitted That Met QC Criteria

June 4, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISIS 766720-CS5
  • 2020-000675-20 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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