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    Summary
    EudraCT Number:2020-000675-20
    Sponsor's Protocol Code Number:ISIS766720-CS5
    National Competent Authority:Romania - National Agency for Medicines and Medical Devices
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-05-19
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedRomania - National Agency for Medicines and Medical Devices
    A.2EudraCT number2020-000675-20
    A.3Full title of the trial
    An Open Label, Randomized, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of IONIS GHR-LRX, an Antisense Inhibitor of the Growth Hormone Receptor, Administered Monthly as Monotherapy in Patients with Acromegaly
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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)
    A.4.1Sponsor's protocol code numberISIS766720-CS5
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorIonis Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportIonis Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIonis Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointIonis Clinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Address2855 Gazelle Court
    B.5.3.2Town/ cityCarlsbad
    B.5.3.3Post codeCA 92010
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1760603-3804
    B.5.5Fax number+1760603-2504
    B.5.6E-mailclinicaltrials@ionisph.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameISIS 766720
    D.3.2Product code ISIS 766720
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available yet
    D.3.9.1CAS number 2131025-83-5
    D.3.9.2Current sponsor codeISIS 766720
    D.3.9.3Other descriptive nameISIS 766720
    D.3.9.4EV Substance CodeSUB191641
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Acromegaly is a chronic disorder caused by GH hypersecretion, most commonly as a result of a GH-secreting pituitary adenoma.
    E.1.1.1Medical condition in easily understood language
    Acromegaly is a hormonal disorder that results from too much growth hormone (GH) in the body. In most cases the overproduction of GH is due to a benign tumor of the pituitary gland called an adenoma.
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10000599
    E.1.2Term Acromegaly
    E.1.2System Organ Class 10014698 - Endocrine disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To evaluate the safety and tolerability of ISIS 766720 subcutaneous (SC) injection as a monotherapy in patients with acromegaly.
    - To evaluate the efficacy of ISIS 766720 SC injection on serum insulin-like growth factor-1 (IGF-1) as a monotherapy in patients with acromegaly.
    E.2.2Secondary objectives of the trial
    - To evaluate the effect of ISIS 766720 SC to normalize serum IGF-1 levels.
    E.2.3Trial contains a sub-study No
    E.3Principal 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 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.
    E.4Principal exclusion criteria
    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 Designee
    20. Patients on anti-diabetes medications must be on a stable dose and regimen for ≥ 3 months prior to Screening. Patients taking insulin can be allowed with prior consultation with the Sponsor Medical Monitor or Designee
    21. Patients on estrogen containing medications must be on a stable dose and regimen for ≥ 3 months prior to Screening
    22.Patients on glucocorticoid replacement used for adrenal insufficiency must be on a stable dose and regimen (increases used to prevent adrenal crisis is permitted) for ≥ 3 months prior to Screening
    23.Use of oral anticoagulants, unless the dose has been stable for 4 weeks prior to the first dose of ISIS 766720 and regular clinical monitoring is performed during the trial
    24.Blood donation of 50 to 499 mL within 30 days of Screening or of > 499 mL within 60 days of Screening and during the trial
    25.Have any other conditions, which, in the opinion of the Investigator and Sponsor would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the Study
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is the percent change in IGF-1 from Baseline to Week 27.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Comparison of percent change in IGF-1 from Baseline to Week 27 between ISIS 766720 80 mg, 120 mg and 160 mg groups in the Per Protocol Set.
    E.5.2Secondary end point(s)
    The secondary efficacy endpoints include:
    • Patients who achieve normalized IGF-1 levels to within 1.2 times gender and age limits at Day 183 (Week 27)
    • Patients who achieve normalized IGF-1 levels to within 1.0 times gender and age limits at Day 183 (Week 27)
    • Change from Baseline in serum IGF-1 over time
    • Percent change from Baseline in serum IGF-1 over time
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Patients who achieve normalized IGF-1 levels to within 1.2 times gender and age limits: at Day 183 (Week 27)
    • Patients who achieve normalized IGF-1 levels to within 1.0 times gender and age limits: at Day 183 (Week 27)
    • Serum IGF-1 level change measured throughout the study
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    Estonia
    Latvia
    Lithuania
    Poland
    Romania
    Italy
    Hungary
    Russian Federation
    Serbia
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 36
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 4
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 40
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-04-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-01-05
    P. End of Trial
    P.End of Trial StatusOngoing
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