Idiopathic intracranial hypertension MedDRA version: 23.1 Level: PT Classification code 10078904 Term: Idiopathic intracranial hypertension System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Exenatide
Product Code: Presendin
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Exenatide acetate
CAS Number: 141758-74-9
Other descriptive name: PT320, PT302 and YH
Sponsors
Invex Therapeutics Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >18 years at the time of consent 2. Diagnosis of new IIH by consensus criteria, including normal structural brain imaging (excluding features of raised intracranial pressure and incidentalomas), including either magnetic resonance venography or computed tomographic venography to exclude thrombosis and no evidence of a secondary causes of raised intracranial pressure 3. Newly diagnosed patients with screening commenced no more than 4 weeks after the diagnostic LP 4. Lumbar puncture opening pressure = 25 cm cerebrospinal fluid (CSF) at diagnosis 5. Presence of bilateral papilloedema (Frisén grade =1). Verification of papilloedema by the OCT Reading Centre. Where there is uncertainty fundus photography and/or ultrasound scan (B scan) of the optic nerves should be conducted for evaluation by the Independent Adjudication Committee (IAC) 6. Perimetric Mean Deviation (PMD) defined as between -2 to -7 decibels (dB) in at least one eye. Eyes meeting this criteria will be defined as ‘study eyes’ 7. Reproducible visual loss present on automated perimetry including no more than 15% false positive responses, (reliability confirmed by the Visual Field Reading Centre) in study eyes 8. Two or more headache days over the 7-day period prior to screening and also the patient must meet this criterion during the 7-day screening period 9. Females of childbearing potential must have a negative pregnancy test and must agree to use a highly effective birth control method (failure rate less than 1% per year when used consistently and correctly during the whole trial duration including the last follow-up visit (12 weeks after ceasing drug). Female patients who are lactating must agree to stop breast-feeding. Or female patients of non-childbearing potential (defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal females defined as 12 months of amenorrhoea [in questionable cases a blood sample with simultaneous follicle stimulation hormone (FSH) 25-140 IE/L and oestradiol =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1.Presence of venous sinus thrombosis on brain imaging by either magnetic resonance or computerised tomographic venography 2. Previous IIH surgery including CSF shunt, optic nerve sheath fenestration or dural venous sinus stent or sub-temporal decompression 3. Previous bariatric surgery within the last 3 months or intention during the trial 4. Abnormal neurological examination (aside from papilloedema and consequent visual loss or sixth or seventh nerve palsy or palsies) 5. Treatment to lower ICP within 1 week prior to screening visit (e.g., acetazolamide, topiramate (including if used as a migraine preventative), diuretics, glucocorticoids (I.V., injectable steroids or oral (including dexamethasone and prednisolone)). (Nasal, inhaled, or topical steroids are allowed) 6. Use of any drugs known to cause intracranial hypertension, including exposure to fluoroquinolones, lithium, vitamin A, or tetracyclines within 2 months prior to diagnostic LP 7.Any disease other than refractive error that causes visual loss in the study eyes. Where there is uncertainly this would be determined by the Independent Adjudication Committee [IAC] 8. Refractive error worse than +/- 6.00 sphere or worse than +/- 3.00 cylinder in study eyes. In addition, participants with myopia of worse than -6.00 D sphere but less than or equal to -8.00 D sphere are eligible if the subject wears a contact lens for all perimetry examinations with the appropriate correction 9. Inability to perform a reliable visual field examination as deemed by the Visual Field Reading Centre in the study eyes. Where there is uncertainly this would be evaluated by the Independent Adjudication Committee [IAC] 10. Does not complete =6 days of electronic/paper trial diary during the 7-day screening period 11. Untreated previously diagnosed obstructive sleep apnoea with historically recorded apnoea-hypopnea index greater than 15 12. Glucagon like peptide-1 receptor agonist within last 4 weeks prior to screening 13. COVID-19 vaccine within 2 weeks prior to screening 14. Allergy/known hypersensitivity to the active substance and/or excipients of the investigational product 15. Has known contraindications to glucagon like peptide-1 (GLP-1) receptor agonists (e.g., ketoacidosis, severe gastrointestinal disease, pancreatitis, renal impairment) which may affect the safety of the patient 16. History of drug-induced immune-mediated thrombocytopenia from exenatide products 17. Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 18. Using any glucose-lowering medication 19. Currently taking warfarin 20. Alanine transaminase (ALT) or aspartate transaminase (AST) =2x the upper limit of normal (ULN), total bilirubin =1.5x ULN, or alkaline phosphatase (ALP) =1.5 ULN at screening (Note – patients with elevated total bilirubin are not excluded if they meet criteria for Gilbert’s syndrome, including: bilirubin is predominantly indirect [with normal direct bilirubin level]; and ALT, AST and ALP =1x ULN) 21. Kidney disease (as defined by serum cystatin C-based estimated glomerular filtration rate [eGFR] <55 mL/min/1.73 m2, calculated at investigator site) 22. Any of the following abnormalities in clinical laboratory tests at screening, as assessed by the central laboratory and confirmed by a single repeat, if deemed necessary: Hemoglobin <10 g/dL (<100 g/L); Platelet count <75 x 109/L (<75,000/mm3) 23. Using recreational or illicit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of Presendin administered subcutaneously once weekly for 24 weeks to patients with IIH, as determined by change in ICP, as measured by LP at baseline and at 24 weeks. The baseline LP is the diagnostic LP. ;Secondary Objective: To determine the effect of Presendin on change in: Perimetric Mean Deviation as measured by Humphrey Visual Field analysis (24-2 SITA-Standard) • Papilloedema by change in optical coherence tomography (retinal nerve fibre layer (RNFL) thickness and optic nerve head size) • Monthly headache days (MHD) • Moderate to severe monthly headache days • Headache responder rate (=50% reduction in monthly headache days) • Headache responder rate (=50% reduction in moderate to severe monthly headache days) • Headache severity • Monthly use of acute headache analgesic medications • Visual acuity • Treatment failure ;Primary end point(s): Change in ICP from baseline to Week 24 measured by LP. The baseline LP is the diagnostic LP. ;Timepoint(s) of evaluation of this end point: week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Perimetric Mean Deviation • Retinal nerve fibre layer (RNFL) thickness • Optic nerve head size • The number of monthly headache days (MHD). Monthly headache days will include all headache days, defined as those with an onset, continuation or recurrence, any severity or phenotype of headache, lasting at least 30 minutes or which require acute headache analgesia • Number of monthly moderate to severe headache days. A moderate/severe headache day will be defined as a day with moderate or severe pain that lasts at least 4 hours or that requires acute headache analgesic medications • Responder rate monthly headache days (defined as a =50% reduction) • Responder rate moderate to severe monthly headache days (defined as a =50% reduction) • Headache severity (assessed by 11-point Numeric Rating Scale [NRS], 0-10 where 0 = no pain and 10 = most severe pain) • Use of acute headache analgesic medications (acute headache analgesics in days per month) • Visual acuity, as measured by logarithm of the minimum angle or resolution (LogMAR) units • Treatment failure, defined as initiation of either medical therapy or a surgical intervention to lower ICP;Timepoint(s) of evaluation of this end point: Refer to Trial assessments in protocol. Table 1 | — |
Countries
Australia, France, Germany, Israel, New Zealand, United Kingdom, United States
Contacts
Public ContactClinical Operations Department
Invex Therapeutics Ltd.
Outcome results
None listed