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

NCT04522180 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: ISIS 766720-CS52020-000675-20NCT04522180
• Study Type: interventional
• Target: 34
• Locations: 10 countries
• Sites: 22

Brief Summary

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.

Conditions

Acromegaly

Keywords

acromegaly; IONIS-GHR-LRx

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27)

  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)

  At Week 27

• Change From Baseline in Serum IGF-1 Over Time

  Up to approximately 80 weeks

• Percent Change From Baseline in Serum IGF-1 Over Time

  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

Study Arms (2)

GHR-LRX 120 mg

EXPERIMENTAL

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 160 mg

EXPERIMENTAL

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

Interventions

GHR-LRX DRUG

GHR-LRX was administered by SC injection.

Also known as: ISIS 766720

GHR-LRX 120 mg; GHR-LRX 160 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females with a documented diagnosis of Acromegaly\* who are 18 to 75 years old (inclusive) at the time of informed consent.
• 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
• At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × ULN, inclusive, adjusted for age and sex.
• Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, abstinent, or using 1 highly effective method of birth control

You may not qualify if:

• Participants who received surgery for pituitary adenoma within the last 3 months before the trial, and/or planning to receive surgery during the trial
• Participants who received radiotherapy for pituitary adenoma within the last 2 years before the trial, and/or planning to receive radiotherapy during the trial
• 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
• Evidence of decompensated cardiac function per medical judgement and/or New York Heart Association (NYHA) Class 3 or 4
• Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment
• Symptomatic cholelithiasis, and/or choledocholithiasis

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (22)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Palm Research Center Inc.

Las Vegas, Nevada, 89148, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Endocrinology Associates, Inc

Columbus, Ohio, 43201, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

East-Tallinn Central Hospital

Tallinn, 10138, Estonia

Location

Tartu University Hospital

Tartu, 50406, Estonia

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122, Italy

Location

Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

Pauls Stradins Clinical University Hospital

Riga, LV-1002, Latvia

Location

Vaidoto Urbanaviciaus Individuali imone

Alytus, 63246, Lithuania

Location

Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos

Kaunas, 50161, Lithuania

Location

Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii

Warsaw, 03-242, Poland

Location

Uniwersytecki Szpital Kliniczny, im. Jana Mikulicza-Radeckiego we Wroclawiu,

Wroclaw, 50-556, Poland

Location

Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.

Wroclaw, 51-162, Poland

Location

Centrul Medical Unirea Bucuresti, Endocrinologie

Bucharest, 060044, Romania

Location

I.M. Sechenov Moscow First State Medical University

Moscow, 119146, Russia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Clinical Center of Vojvodina

Novi Sad, 21000, Serbia

Location

MeSH Terms

Conditions

Acromegaly

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc.
• Organization: Ionis Pharmaceuticals, Inc.

globalregulatoryaffairs@ionisph.com

760-603-2346

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: August 21, 2020
• Study Start: January 4, 2021
• Primary Completion: July 15, 2022
• Study Completion: May 4, 2023
• Last Updated: October 3, 2024
• Results First Posted: October 3, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); RU (1); IT (2); HU (1); PL (3); RO (1); ES (2); US (7); LI (2); LA (1)