Acromegaly is a chronic disorder caused by GH hypersecretion, most commonly as a result of a GH-secreting pituitary adenoma. MedDRA version: 20.0 Level: PT Classification code 10000599 Term: Acromegaly System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Product Name: ISIS 766720
Product Code: ISIS 766720
Pharmaceutical Form: Solution for injection
INN or Proposed INN: not yet available
CAS Number: 2131025-83-5
Current Sponsor code: ISIS 766720
Conce
Sponsors
Ionis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements 2. Males or females with documented diagnosis of Acromegaly*. Aged 18 to 75 years old (inclusive) at the time of informed consent * Defined as a previous diagnosis of GH-secreting adenoma by surgical pathology; or the presence of a pituitary adenoma on magnetic resonance imaging (MRI) or computed tomography (CT) scan (if MRI is contraindicated) and serum IGF-1 levels above the upper limit of normal for age and sex at time of diagnosis (serum IGF-1 level and MRI at diagnosis will be collected in the CRF). 3. 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. In accordance with US approved prescribing information, the maximal dose recommended per the package insert for lanreotide Autogel is 120 mg very 28 days and for octreotide LAR is 40 mg every 28 days (the reason for the maximally tolerated dose of SRL will be collected in the CRF). SRL dose should not exceed the maximum dose as approved in the local region (as indicated in the SRL label). Prior use of other medications for treating acromegaly (pasireotide, dopamine agonist or pegvisomant) is allowed but not within 6 weeks of screening * Patients who are on a stable monthly dosing regimen, but not exactly every 28 days will be considered for inclusion to this study. Patients who are on a stable regimen, that is not monthly e.g., every 3 weeks or every 6 weeks are excluded. 4. At Screening, serum IGF-1 (performed at central lab) between 1.3 to 5 x ULN, inclusive, adjusted for age and sex 5. Females must be non-pregnant and non-lactating, and either a. surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) b. post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females = 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved); c. abstinent* or d. Women of childbearing potential (WOCBP) should agree to taking all precaution to avoid pregnancy during the trial period (including post-treatment), including agreeing to receive pregnancy testing before each monthly dose, using 1 highly effective methods of birth control, from the time of signing the informed consent form until 14 weeks after the last dose of Study Drug administration Males must be surgically sterile, abstinent or, if engaged in sexual relations with a female of child-bearing potential, the patient must be using 1 highly effective contraceptive method from the time of signing the informed consent form until 14 weeks after the last dose of Study Drug 6. Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) for at least 24 hours prior to study visits 7. Willing to refrain from alcohol or tobacco use for 8 hours prior to study visits Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Clinically-significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of screening, major non-pituitary surgery within 3 months of screening) or from Screening physical examination 2. Patients who received surgery for pituitary adenoma within the last 6 months before the trial, and/or planning to receive surgery during the trial 3. Patients who received radiotherapy for pituitary adenoma within the last 7 years before the trial, and/or planning to receive radiotherapy during the trial 4. Patients 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 or CT scan protocol at Screening or within 6 months of screening 5. Evidence of decompensated cardiac function per medical judgement and/or NYHA class 3 or 4 6. Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment 7. Symptomatic cholelithiasis, and/or choledocholithiasis 8. Have a diagnosis of Gilbert’s disease 9. Patients with history of hypoglycemia unawareness (who have had > 3 severe episodes in the past 6 months) or documented reactive hypoglycemia 10. Screening laboratory results as follows, or any other clinically-significant abnormalities in screening laboratory values that would render a patient unsuitable for inclusion. (abnormalities may be retested for eligibility purposes) a. Urine protein/creatinine (P/C) ratio = 500 mg/g. In the event of P/C ratio above this threshold eligibility may be confirmed by a quantitative total urine protein measurement of 1.2 x ULN, bilirubin > ULN; alkaline phosphatase > 3 x ULN d. eGFR 1.8 mg/dL in males and > 1.5 mg/dL in females e. Platelet count 10% h. Abnormal morning cortisol test consistent with symptomatic adrenal insufficiency based on Investigator judgement 11. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1 12. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator 13. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B 14. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, follicular Stage 1 or papillary thyroid cancer that has been successfully treated; patients with a history of other malignancies that have been treated with curative intent and which have no recurrence within 5 years may also be eligible if approved by the Sponsor medical monitor 15. Treatment with another investigational drug, biological agent, or device within 1 month of screening, or 5 half-lives of investigational agent, whichever is longer 16. Treatment with any non-ION- or ISIS-oligonucleotide (including siRNA) at any time or prior treatment with an ION- or ISIS-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Comparison of percent change from Baseline to PTWk5 (28 days after last dose) in serum IGF-1 between ISIS 766720 80 mg group and pooled placebo group in the Per Protocol Set. Safety Analyses: The treatment-emergent adverse events (TEAEs) and SAEs analysed the whole duration of the study. Laboratory tests including chemistry panel, CBC with differential, coagulation panel, complement etc., will be summarized by study visits for each treatment group. ;Secondary Objective: To evaluate the effect of ISIS 766720 to normalize serum IGF-1 levels.;Main Objective: - To evaluate the efficacy of ISIS 766720 subcutaneous injection on serum insulin-like growth factor 1 (IGF-1) vs. placebo as an add-on therapy to long acting somatostatin receptor ligands (SRL) octreotide or lanreotide. - To evaluate the safety and tolerability of ISIS 766720 subcutaneous injection vs. placebo on add-on therapy of SRL.;Primary end point(s): The primary efficacy endpoint is the percent change in IGF-1 from Baseline to 28 Days after last dose (PTWk5 Visit). The safety endpoints include: •Adverse events •Vital signs and weight and calculated BMI •Physical examination •Clinical laboratory tests •ECG •Use of concomitant medication | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints include: • Proportion of patients achieve normalized IGF-1 levels to within 1.2 times of gender and aged limits at 28 days after last dose (PTWk5 Visit) • Proportion patients achieve normalized IGF-1 levels to within 1.0 times of gender and aged limits at 28 days after last dose (PTWk5 Visit) • Change from Baseline in serum IGF-1 over time • Percent change from Baseline in serum IGF-1 over time ;Timepoint(s) of evaluation of this end point: • Measure of IGF-1 level at 28 days after last dose (PTWk5 Visit) • Serum IGF-1 level change measured throughout the study | — |
Countries
Austria, Czech Republic, Hungary, Lithuania, Poland, Romania, Russian Federation, Serbia, United States
Contacts
Public ContactIonis Clinical Trial Information
Ionis Pharmaceuticals, Inc.
Outcome results
None listed