An open label study to assess the safety, tolerability, and efficacy of the study drug, ISIS 766720, administered monthly in patients with acromegaly (a hormonal disorder that results from too much growth hormone in the body)
- Conditions
- Acromegaly is a chronic disorder caused by GH hypersecretion, most commonly as a result of a GH-secreting pituitary adenoma.MedDRA version: 20.0Level: PTClassification code 10000599Term: AcromegalySystem Organ Class: 10014698 - Endocrine disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2020-000675-20-RO
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 40
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 a documented diagnosis of Acromegaly* who are 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 identified 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 (ULN) for age and sex at time of diagnosis (serum IGF-1 level and imaging at diagnosis will be collected in the case report forms [CRF])
3.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: 4 months
pasireotide LAR: 4 months
lanreotide (all formulations): 4 months
4. At Screening, serum IGF-1 (performed at central lab) between 1.3 to 5 × ULN, inclusive, adjusted for age and sex. IGF 1 can be repeated once and averaged to determine eligibility if the initial result is between 1.1-1.3 × ULN, or between 5-5.3 × ULN
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 follicle-stimulating hormone (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 method of birth control from the time of signing the informed consent form (ICF) until 14 weeks after the last dose of ISIS 766720 administration
Males must be either:
e. surgically sterile
f. abstinent or
g. if engaged in sexual relations with a female of child-bearing potential, the patient must be using a highly effective contraceptive method from the time of signing the ICF until 14 weeks after the last dose of ISIS 766720
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 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
1. Clinically significant abnormalities in medical history or physical examination
2. Patients who received surgery for pituitary adenoma within the last 3 months before the trial, and/or planning to receive surgery during the trial
3. Patients who received radiotherapy for pituitary adenoma within the last 2 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 protocol at Screening or within 3 months of Screening. CT scan is allowed if MRI is contraindicated.
5. Evidence of decompensated cardiac function per medical judgement and/or New York Heart Association (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 Syndrome
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 described in the protocol, or any other CS abnormalities in Screening laboratory values that would render a patient unsuitable for inclusion (abnormalities may be retested for eligibility purposes)
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. Active infection with human immunodeficiency virus (HIV), hepatitis C (HCV) or hepatitis B (HBV) diagnosed by initial serology testing and confirmed with RNA testing, or prior treatment for HCV. Patients at Screening who test positive by serology, but negative by RNA may be allowed in consultation with the Sponsor Medical Monitor or Designee
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 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 or Designee
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 small interfering ribonucleic acid [siRNA]) at any time or prior treatment with an ION- or ISIS-oligonucleotide within 9 months of Screening. Patients that have previously received only a single-dose of an ION or ISIS-oligonucleotide as part of a clinical study may be included as long as duration = 4 months has elapsed since dosing
17. History of bleeding diathesis or coagulopathy
18. Recent history of, or current drug or alcohol abuse that could affect study compliance per Investigator judgment
19. Patients may not have chronic systemic use of weight loss medications (except GLP-1 agonist or SGLT2 inhibitors) or participate in weight loss programs within 2 months before Screening. Patients taking GLP-1 agonist or SGLT2 inhibitors indicated for weight loss maybe allowed with prior consultation with the Sponsor Medical Monitor or De
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method