A Trial to Determine the Efficacy and Safety of Presendin in IIH

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 ICP and incidentalomas), including either magneticresonance venography or computed tomographic venography to exclude thrombosis and noevidence of a secondary causes of raised ICP.
3. Newly diagnosed patients with screening commenced no more than 4 weeks after thediagnostic LP.
4. Lumbar puncture opening pressure ≥25 cm cerebrospinal fluid (CSF) at diagnosis.
5. Presence of bilateral papilloedema (Frisén grade ≥1). Verification of papilloedema bythe OCT Reading Centre. Where there is uncertainty fundus photography and/orultrasound scan (B scan) of the optic nerves should be conducted for evaluation by theIndependent Adjudication Committee (IAC).
6. Perimetric Mean Deviation defined as between -2 to -7 decibels (dB) in at least oneeye. Eyes meeting this criterion will 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) instudy eyes.
8. Two or more headache days over the 7-day period prior to screening and also thepatient must meet this criterion during the 7-day screening period.
9. Females of childbearing potential must have a negative pregnancy test and must agreeto use a highly effective birth control method (failure rate less than 1% per yearwhen used consistently and correctly) during the whole trial duration including thelast follow-up visit (12 weeks after ceasing drug). Female patients who are lactatingmust 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 casesa blood sample with simultaneous follicle stimulation hormone 25-140 IE/L andoestradiol <200 pmol/L is confirmatory]).
10. Male patients with a female partner of childbearing potential must commit to practicemethods of contraception (e.g., condom, vasectomy) and abstain from sperm donationduring the trial including the last follow-up visit (12 weeks after ceasing drug).Their partners, if they are women of childbearing potential, must agree to practicecontraception and to use a highly effective method of contraception during the trial,including the last follow-up visit (12 weeks after ceasing drug).
11. Able to provide written informed consent.

Exclusion Criteria: IIH-related exclusion criteria:

1. Presence of venous sinus thrombosis on brain imaging by either magnetic resonance orcomputerised tomographic venography.
2. Previous IIH surgery including CSF shunt, optic nerve sheath fenestration or duralvenous 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 lossor 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 tofluoroquinolones, lithium, vitamin A, or tetracyclines within 2 months prior todiagnostic LP. Vision-related exclusion criteria:
7. Any disease other than refractive error that causes visual loss in the study eyes.Where there is uncertainty this would be determined by the IAC.
8. Refractive error worse than +/- 6.00 sphere or worse than +/- 3.00 cylinder in studyeyes. In addition, participants with myopia of worse than -6.00 D sphere but less thanor equal to -8.00 D sphere are eligible if the subject wears a contact lens for allperimetry examinations with the appropriate correction.
9. Inability to perform a reliable visual field examination as deemed by the Visual FieldReading Centre in the study eyes. Where there is uncertainty this would be evaluatedby the IAC. Headache-related exclusion criteria:
10. Does not complete ≥6 days of electronic/paper trial diary during the 7-day screeningperiod. Other exclusion criteria:
11. Untreated previously diagnosed obstructive sleep apnoea with historically recordedapnoea-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 theinvestigational 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. Using any glucose-lowering medication.
17. Currently taking warfarin.
18. Alanine transaminase (ALT) or aspartate transaminase (AST) ≥2x the upper limit ofnormal (ULN), total bilirubin ≥1.5x ULN, or alkaline phosphatase (ALP) ≥1.5 ULN atscreening. Note - patients with elevated total bilirubin are not excluded if they meetcriteria for Gilbert's syndrome, including: bilirubin is predominantly indirect (withnormal direct bilirubin level); and ALT, AST and ALP ≤1x ULN).
19. Kidney disease (as defined by serum cystatin C-based estimated glomerular filtrationrate <55 mL/min/1.73 m², calculated at investigator site).
20. Any of the following abnormalities in clinical laboratory tests at screening, asassessed by the central laboratory and confirmed by a single repeat, if deemednecessary: Haemoglobin <10 g/dL (<100 g/L); Platelet count <75 x 10⁹/L (<75,000/mm³).
21. Using recreational or illicit drugs at the time of signing the informed consent, orrecent history (within the last year) of drug or alcohol abuse or dependence accordingto the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria,that in the opinion of the investigator puts the patient at risk.
22. Is unable to self-administer the trial medication (or unable to administer trialmedication with support) after receiving training during the screening period.
23. History of any clinically significant disease or disorder that, in the opinion of theinvestigator, may either put the patient at risk because of participation in the trialor influence the results or the patient's ability to participate in the trial.
24. Any contraindication to lumbar puncture procedure in the opinion of the investigator.
25. Has participated in any other interventional trial within 1 month prior to thescreening visit.
26. Is pregnant or breastfeeding. Note: Use of headache preventative medication is allowed at enrolment (except fortopiramate). Changes to headache preventative medication during the trial should be made inconsultation with the IAC.