Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in Patients With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03548415

Collaborator

(none)

Enrollment

Locations

Arms

30.6

Actual Duration (Months)

1.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose is to assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in up to 60 Patients with Acromegaly

Condition or Disease	Intervention/Treatment	Phase
Acromegaly	Drug: IONIS-GHR-LRx Drug: Placebo	Phase 2

Detailed Description

This short-term study will assess changes in serum insulin-like growth factor 1 (IGF-1) over a 16-week treatment period in a patient population diagnosed with Acromegaly being treated with Long-acting Somatostatin Receptor Ligands (SRL)

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of ISIS 766720 (IONIS-GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor) Administered Once Every 28 Days for 16 Weeks in Patients With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands (SRL)

Actual Study Start Date :

Sep 13, 2018

Actual Primary Completion Date :

Apr 2, 2021

Actual Study Completion Date :

Apr 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IONIS-GHR-LRx Single Dose of IONIS GHR-LRx administered subcutaneously once every 28 days for 16 weeks	Drug: IONIS-GHR-LRx Single Dose of IONIS GHR-LRx administered subcutaneously once every 28 days for 16 weeks
Placebo Comparator: Placebo Placebo (sterile saline 0.9%) Calculated volume to match active comparator administered subcutaneously every 28 days for 16 weeks	Drug: Placebo Placebo (sterile saline 0.9%) Calculated volume to match active comparator administered subcutaneously every 28 days for 16 weeks

Arm

Intervention/Treatment

Experimental: IONIS-GHR-LRx

Single Dose of IONIS GHR-LRx administered subcutaneously once every 28 days for 16 weeks

Drug: IONIS-GHR-LRx

Single Dose of IONIS GHR-LRx administered subcutaneously once every 28 days for 16 weeks

Placebo Comparator: Placebo

Placebo (sterile saline 0.9%) Calculated volume to match active comparator administered subcutaneously every 28 days for 16 weeks

Drug: Placebo

Placebo (sterile saline 0.9%) Calculated volume to match active comparator administered subcutaneously every 28 days for 16 weeks

Outcome Measures

Primary Outcome Measures

Efficacy of IONIS GHR-LRx as percent change in serum IGF-1 from Baseline to 28 days after last dose [Baseline and 28 days after the last dose]
Incidence and severity of adverse events that are related to treatment with IONIS GHR-LRx. [Up to 211 days]

Secondary Outcome Measures

Proportion of patients achieving normalized IGF-1 levels to within 1.2 times of gender and age limits at 28 days after last dose [28 days after the last dose]
Proportion of patients achieving normalized IGF-1 levels to within 1.0 times of gender and age limits at 28 days after last dose [28 days after the last dose]
Change from Baseline in serum IGF-1 over time [Up to 31 weeks]
Percent change from Baseline in Serum IGF-1 over time [Up to 31 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or females with documented diagnosis of Acromegaly, aged 18-75 years old (inclusive) at the time of informed consent
Patients must be on stable maximum or maximally tolerated dose of SRL (Lanreotide Autogel or Octreotide LAR, per treating physician judgment) every 28 days for a minimum of 3 months prior to screening and will be required to continue their stable dose of SRL throughout the study. Prior use of other medications for treating acromegaly is allowed but not within 6 weeks of screening.
At Screening, serum IGF-1 (performed at central lab) between 1.3 to 5 x 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

Exclusion Criteria:

Patients who received surgery for pituitary adenoma within the last 6 months before the trial, or planning to receive surgery during the trial
Patients who received radiotherapy for pituitary adenoma within the last 3 years before the trial, and/or planning to receive radiotherapy during the trial
Patients with pituitary tumor that, per Investigator judgement, is worsening as assessed by pituitary/sellar MRI protocol at Screen or within 6 months of screening
Evidence of decompensated cardiac function per medical judgement and/or NYHA class 3 or 4
Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment
Patients may not have chronic systemic use of glucocorticoids, weight loss medications or participate in weight loss programs within 2 months before randomization and during study participation.
Patients on anti-diabetes medication or estrogen containing medications must be on a stable dose and regimen for >= 3 months prior to screening and throughout the trial
Patients taking GLP-1 agonists or insulin can be allowed with prior consultation with the Sponsor Medical Monitor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham (UAB)	Birmingham	Alabama	United States	35294
2	St. Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
3	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
4	University of Colorado Denver - Division of Endocrinology, Metabolism & Diabetes	Aurora	Colorado	United States	80045
5	Northwestern University	Chicago	Illinois	United States	60611
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
7	Palm Research Center, Inc.	Las Vegas	Nevada	United States	89148
8	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
9	Cleveland Clinic	Cleveland	Ohio	United States	44195
10	Oregon Health & Science University (OHSU)	Portland	Oregon	United States	97239
11	University Clinic for Internal Medicine	Innsbruck		Austria	6020
12	Fakultni nemocnice Kralovske Vinohrady	Praha 10		Czechia	100 34
13	Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly	Budapest		Hungary	1062
14	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
15	Szeged University - Szent-Gyorgyi Albert Clinical Center - I. Belgyógyászati Klinika (Internal Medicine)	Szeged		Hungary	6720
16	Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos - Hospital of Oncology	Kaunas		Lithuania	50009
17	Vaidoto Urbanaviciaus Individuali imone - Endokrinologijos klinika	Vilnius		Lithuania	08661
18	B_Serwis Popenda Sp. J. Specjalistyczna Przychodnia Lekarsk	Chorzow		Poland	41-500
19	Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach	Katowice		Poland	40-952
20	Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o. o.	Krakow		Poland	31-011
21	Twoja Przychodnia - Centrum Medyczne Nowa Sol	Nowa Sol		Poland	67-00
22	Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii	Warszawa		Poland	03-242
23	Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.	Wroclaw		Poland	51-162
24	Centrul Medical Unirea - Bucuresti, Endocrinologie	Bucharest		Romania	010567
25	Spitalul Clinic Judetean de Urgenta Cluj - Napoca	Cluj-Napoca		Romania	400349
26	Spitalul Clinic Judetean Mures	Targu-Mures		Romania	540142
27	Spitalul Clinic Judetean de Urgenta Timisoara	Timisoara		Romania	300723
28	Multi-field Medical Clinic Anturium LLC	Barnaul		Russian Federation	656043
29	Interregional Clinical Diagnostic Center	Kazan		Russian Federation	420101
30	Kuzbass Clinical Hospital n.a. S.V. Belyaev	Kemerovo		Russian Federation	650066
31	Federal State Budget Institution "National Medical Research Center of Endocrinology" of the Ministry of Healthcare of the Russian Federation	Moscow		Russian Federation	117036
32	I.M. Sechenov Moscow First State Medical University	Moscow		Russian Federation	119992
33	Novosibirsk State Regional Clinical Hospital	Novosibirsk		Russian Federation	630087
34	Orenburg Regional Clinical Hospital, Endocrinology Department	Orenburg		Russian Federation	460018
35	Rostov State Medical University	Rostov-On-Don		Russian Federation	344022
36	Almazov National Medical Research Centre	St. Petersburg		Russian Federation	194156
37	State Budget Healthcare Institution of the Tver Region	Tver		Russian Federation	170036
38	Clinical Center of Serbia	Belgrade		Serbia	11000

Sponsors and Collaborators

Ionis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ionis Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT03548415

Other Study ID Numbers:

ISIS 766720-CS2
2017-004259-22

First Posted:

Jun 7, 2018

Last Update Posted:

Mar 29, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Ionis Pharmaceuticals, Inc.

Acromegaly, IONIS-GHR-LRx

Additional relevant MeSH terms:

Acromegaly

Study Results

No Results Posted as of Mar 29, 2022