Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in Participants With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands
- Registration Number
- NCT03548415
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
- Males or females with documented diagnosis of acromegaly, aged 18-75 years old (inclusive) at the time of informed consent
- 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.
- 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
- Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, abstinent, or using 1 highly effective method of birth control
- Participants who received surgery for pituitary adenoma within the last 6 months before the trial, or planning to receive surgery during the trial
- Participants who received radiotherapy for pituitary adenoma within the last 3 years before the trial, and/or planning to receive radiotherapy during the trial
- 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
- 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
- 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.
- 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
- Participants taking glucagon-like peptide 1 (GLP-1) agonists or insulin can be allowed with prior consultation with the Sponsor Medical Monitor
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort D: IONIS GHR-LRx, 160 mg IONIS-GHR-LRx Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. Cohort C: IONIS GHR-LRx, 120 mg IONIS-GHR-LRx Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks. Placebo Placebo Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks. Cohort A: IONIS GHR-LRx, 60 mg IONIS-GHR-LRx Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks. Cohort B: IONIS GHR-LRx, 80 mg IONIS-GHR-LRx Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With TEAEs Related to Clinically Significant Electrocardiogram (ECG) Findings Up to 211 days ECG assessments included QT, QRS duration, PR interval, ventricular rate, QTcB, QTcF.
Percent Change in Serum Insulin-like Growth Factor-1 (IGF-1) From Baseline to 28 Days After Last Dose Baseline and 28 days after last dose (Day 141) 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.
Number of Participants With TEAEs Related to Clinically Significant Physical Examination Findings Up to 211 days Physical examination included weight and body mass index (BMI) recorded throughout the study. Clinical significance was determined by the investigator.
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings Up to 211 days 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Up to 211 days 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.
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings Up to 211 days Vitals signs included blood pressure, heart rate, respiratory rate, and temperature recorded throughout the study. Clinical significance was determined by the investigator.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Serum IGF-1 Over Time Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 141, 155, 183, and 211 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.
Number of Participants Achieving Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at 28 Days After Last Dose Baseline to 28 days after last dose (Day 141) 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.
Percent Change From Baseline in Serum IGF-1 Over Time Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 155, 183, and 211 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.
Number of Participants Achieving Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at 28 Days After Last Dose Baseline to 28 days after last dose (Day 141) 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.
Trial Locations
- Locations (32)
University of Alabama at Birmingham (UAB)
🇺🇸Birmingham, Alabama, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Palm Research Center, Inc.
🇺🇸Las Vegas, Nevada, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Oregon Health & Science University (OHSU)
🇺🇸Portland, Oregon, United States
Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly
🇭🇺Budapest, Hungary
Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos - Hospital of Oncology
🇱🇹Kaunas, Lithuania
Vaidoto Urbanaviciaus Individuali imone - Endokrinologijos klinika
🇱🇹Vilnius, Lithuania
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
Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.
🇵🇱Wroclaw, Poland
Twoja Przychodnia - Centrum Medyczne Nowa Sol
🇵🇱Nowa Sol, Poland
Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
🇵🇱Warszawa, Poland
Centrul Medical Unirea - Bucuresti, Endocrinologie
🇷🇴Bucharest, Romania
Spitalul Clinic Judetean de Urgenta Cluj - Napoca
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic Judetean Mures
🇷🇴Targu-Mures, Romania
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
Orenburg Regional Clinical Hospital, Endocrinology Department
🇷🇺Orenburg, Russian Federation
Almazov National Medical Research Centre
🇷🇺St. Petersburg, Russian Federation
Rostov State Medical University
🇷🇺Rostov-On-Don, Russian Federation
State Budget Healthcare Institution of the Tver Region
🇷🇺Tver, Russian Federation
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Spitalul Clinic Judetean de Urgenta Timisoara
🇷🇴Timisoara, Romania
Novosibirsk State Regional Clinical Hospital
🇷🇺Novosibirsk, Russian Federation
Multi-field Medical Clinic Anturium LLC
🇷🇺Barnaul, Russian Federation
Szeged University - Szent-Gyorgyi Albert Clinical Center - I. Belgyógyászati Klinika (Internal Medicine)
🇭🇺Szeged, Hungary