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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03548415
Other study ID # ISIS 766720-CS2
Secondary ID 2017-004259-22
Status Completed
Phase Phase 2
First received
Last updated
Start date September 13, 2018
Est. completion date April 2, 2021

Study information

Verified date October 2022
Source Ionis Pharmaceuticals, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study was to assess the safety, tolerability, and efficacy of IONIS-GHR-LRx in up to 60 participants with acromegaly.


Description:

This short-term study assessed changes in serum insulin-like growth factor 1 (IGF-1) over a 16-week treatment period in a participant population diagnosed with acromegaly being treated with long-acting somatostatin receptor ligands (SRL).


Recruitment information / eligibility

Status Completed
Enrollment 43
Est. completion date April 2, 2021
Est. primary completion date February 18, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: 1. Males or females with documented diagnosis of acromegaly, aged 18-75 years old (inclusive) at the time of informed consent 2. Participants 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. 3. At Screening, serum insulin-like growth factor 1 (IGF-1) (performed at central lab) between 1.3 to 5 x upper limit of normal (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 6 months before the trial, or planning to receive surgery during the trial 2. Participants who received radiotherapy for pituitary adenoma within the last 3 years before the trial, and/or planning to receive radiotherapy during the trial 3. Participants with pituitary tumor that, per Investigator judgement, is worsening as assessed by pituitary/sellar magnetic resonance imaging (MRI) protocol at Screen or within 6 months of screening 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. Participants 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. 7. Participants 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 8. Participants taking glucagon-like peptide 1 (GLP-1) agonists or insulin can be allowed with prior consultation with the Sponsor Medical Monitor

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
IONIS-GHR-LRx
IONIS GHR-LRx administered subcutaneously.
Placebo
Placebo administered subcutaneously.

Locations

Country Name City State
Hungary Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly Budapest
Hungary Debreceni Egyetem Klinikai Kozpont Debrecen
Hungary Szeged University - Szent-Gyorgyi Albert Clinical Center - I. Belgyógyászati Klinika (Internal Medicine) Szeged
Lithuania Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos - Hospital of Oncology Kaunas
Lithuania Vaidoto Urbanaviciaus Individuali imone - Endokrinologijos klinika Vilnius
Poland B_Serwis Popenda Sp. J. Specjalistyczna Przychodnia Lekarsk Chorzow
Poland Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach Katowice
Poland Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o. o. Krakow
Poland Twoja Przychodnia - Centrum Medyczne Nowa Sol Nowa Sol
Poland Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii Warszawa
Poland Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p. Wroclaw
Romania Centrul Medical Unirea - Bucuresti, Endocrinologie Bucharest
Romania Spitalul Clinic Judetean de Urgenta Cluj - Napoca Cluj-Napoca
Romania Spitalul Clinic Judetean Mures Targu-Mures
Romania Spitalul Clinic Judetean de Urgenta Timisoara Timisoara
Russian Federation Multi-field Medical Clinic Anturium LLC Barnaul
Russian Federation Interregional Clinical Diagnostic Center Kazan
Russian Federation Kuzbass Clinical Hospital n.a. S.V. Belyaev Kemerovo
Russian Federation Federal State Budget Institution "National Medical Research Center of Endocrinology" of the Ministry of Healthcare of the Russian Federation Moscow
Russian Federation I.M. Sechenov Moscow First State Medical University Moscow
Russian Federation Novosibirsk State Regional Clinical Hospital Novosibirsk
Russian Federation Orenburg Regional Clinical Hospital, Endocrinology Department Orenburg
Russian Federation Rostov State Medical University Rostov-On-Don
Russian Federation Almazov National Medical Research Centre St. Petersburg
Russian Federation State Budget Healthcare Institution of the Tver Region Tver
Serbia Clinical Center of Serbia Belgrade
United States University of Alabama at Birmingham (UAB) Birmingham Alabama
United States Northwestern University Chicago Illinois
United States Palm Research Center, Inc. Las Vegas Nevada
United States Palm Research Center, Inc. Las Vegas Nevada
United States Memorial Sloan Kettering Cancer Center New York New York
United States St. Joseph's Hospital and Medical Center Phoenix Arizona
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,  Hungary,  Lithuania,  Poland,  Romania,  Russian Federation,  Serbia, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percent Change in Serum Insulin-like Growth Factor-1 (IGF-1) From Baseline to 28 Days After Last Dose IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Percent change from Baseline in IGF-1 levels was measured at Day 141. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative percent change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic (PD) activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively. Baseline and 28 days after last dose (Day 141)
Primary Number of Participants With Treatment-emergent Adverse Events (TEAEs) A TEAE was defined as an adverse event that occurred after the initiation of study drug dosing and before the end of the follow-up period. Up to 211 days
Primary Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings Vitals signs included blood pressure, heart rate, respiratory rate, and temperature recorded throughout the study. Clinical significance was determined by the investigator. Up to 211 days
Primary Number of Participants With TEAEs Related to Clinically Significant Physical Examination Findings Physical examination included weight and body mass index (BMI) recorded throughout the study. Clinical significance was determined by the investigator. Up to 211 days
Primary Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings Clinical laboratory assessments included clinical chemistry, hematology, and urinalysis. Clinically-significant abnormal laboratory values were reported as TEAEs if the results may, in the opinion of the Investigator, constitute or be associated with an AE. Up to 211 days
Primary Number of Participants With TEAEs Related to Clinically Significant Electrocardiogram (ECG) Findings ECG assessments included QT, QRS duration, PR interval, ventricular rate, QTcB, QTcF. Up to 211 days
Secondary Number of Participants Achieving Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at 28 Days After Last Dose Normalization of circulating IGF-1 is a validated marker for the treatment of acromegaly. IGF-1 assessments were based on a single serum sample taken in fasting conditions, prior to the study drug administration. Normal IGF-1 levels for a participant differ based on age and gender. Number of participants with a normal IGF-1 level which were 1.2 times within gender and age limits after 28 days of the last dose (Day 141) are presented. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively. Baseline to 28 days after last dose (Day 141)
Secondary Number of Participants Achieving Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at 28 Days After Last Dose Normalization of circulating IGF-1 is a validated marker for the treatment of acromegaly. IGF-1 assessments were based on a single serum sample taken in fasting conditions, prior to the study drug administration. Normal IGF-1 levels for a participant differ based on age and gender. Number of participants with a normal IGF-1 level which were 1.0 times within gender and age limits after 28 days of the last dose (Day 141) are presented. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively. Baseline to 28 days after last dose (Day 141)
Secondary Change From Baseline in Serum IGF-1 Over Time IGF-1 is a hormone that manages the effects of GH in the body. Change from Baseline in IGF-1 levels was measured at multiple timepoints up to Day 211. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively. Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 141, 155, 183, and 211
Secondary Percent Change From Baseline in Serum IGF-1 Over Time IGF-1 is a hormone that manages the effects of GH in the body. Percent change from Baseline in IGF-1 levels was measured at multiple timepoints up to Day 211. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative percent change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively. Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 155, 183, and 211
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