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

Acromegaly Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04522180
• Other study ID #: ISIS 766720-CS5
• Secondary ID: 2020-000675-20
• Status: Completed
• Phase: Phase 2
• Start date: January 4, 2021
• Est. completion date: May 4, 2023

Study information

• Verified date: June 2023
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: May 4, 2023
• Est. primary completion date: July 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acromegaly

Intervention

Drug:
• IONIS-GHR-LRx
IONIS-GHR-LRx will be administered by SC injection.

Locations

Country	Name	City	State
Estonia	East-Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano	Milano
Italy	Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore	Roma
Latvia	Pauls Stradins Clinical University Hospital	Riga
Lithuania	Vaidoto Urbanaviciaus Individuali imone	Alytus
Lithuania	Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos	Kaunas
Poland	Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii	Warszawa
Poland	Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.	Wroclaw
Poland	Uniwersytecki Szpital Kliniczny, im. Jana Mikulicza-Radeckiego we Wroclawiu,	Wroclaw
Romania	Centrul Medical Unirea Bucuresti, Endocrinologie	Bucharest
Russian Federation	I.M. Sechenov Moscow First State Medical University	Moscow
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Center of Vojvodina	Novi Sad
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Endocrinology Associates, Inc	Columbus	Ohio
United States	Palm Research Center Inc.	Las Vegas	Nevada
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oregon Health & Science University (OHSU)	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Estonia,  Hungary,  Italy,  Latvia,  Lithuania,  Poland,  Romania,  Russian Federation,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Insulin-like Growth Factor I (IGF-1) to Week 27		Up to Week 27
Secondary	Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at Day 183 (Week 27)		At Week 27
Secondary	Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at Day 183 (Week 27)		At Week 27
Secondary	Change From Baseline in Serum IGF-1 Over Time		Up to approximately 80 weeks
Secondary	Percent Change From Baseline in Serum IGF-1 Over Time		Up to approximately 80 weeks