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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05347147




Registration number
NCT05347147
Ethics application status
Date submitted
20/04/2022
Date registered
26/04/2022

Titles & IDs
Public title
A Trial to Determine the Efficacy and Safety of Presendin in IIH
Scientific title
A Phase III Randomised, Placebo-controlled, Double-blind, Multi-centre, Clinical Trial to Determine the Efficacy and Safety of Presendin in Idiopathic Intracranial Hypertension
Secondary ID [1] 0 0
INVEX-CLIN-IIH-301
Universal Trial Number (UTN)
Trial acronym
IIH EVOLVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Intracranial Hypertension 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Presendin
Treatment: Drugs - Placebo

Experimental: Presendin - 2.0 mg

Placebo comparator: Placebo -


Treatment: Drugs: Presendin
Presendin is supplied as 2 parts, one vial consisting of a drug part (white or greyish white powder in a clear vial) and one pre-filled syringe containing the diluent part (colourless liquid). The drug part is suspended in the diluent part solution and administered SC as a suspension.

Treatment: Drugs: Placebo
Placebo is supplied as 2 parts (visually identical to the Presendin vial and pre-filled diluent syringe). The drug part will exclude the active pharmaceutical ingredient (exenatide acetate) and the diluent part will be the same as the active treatment diluent. The drug part is suspended in the diluent part solution and administered SC as a suspension.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in ICP From Baseline to Week 24 Measured by Lumbar Puncture (LP), Where a Higher LP Value Indicates Greater ICP
Timepoint [1] 0 0
Baseline to Week 24
Secondary outcome [1] 0 0
Change in Perimetric Mean Deviation (PMD), Measured by Humphrey Visual Field (HVF) Analysis (24-2 SITA-Standard), Where a Larger Negative Result Indicates Greater Visual Loss
Timepoint [1] 0 0
Baseline to Week 24
Secondary outcome [2] 0 0
Papilloedema by Change in Retinal Nerve Fibre Layer (RNFL) Thickness, With a Greater Thickness of RNFL Indicating Greater Swelling and Greater Extent of Papilloedema
Timepoint [2] 0 0
Baseline to Week 24
Secondary outcome [3] 0 0
Papilloedema by Percent Change in Optic Nerve Head Size, Measured by Optical Coherence Tomography (OCT), Where a Larger Optic Nerve Head Size Reflects Greater Swelling and a Greater Extent of Papilloedema
Timepoint [3] 0 0
Baseline to Week 24
Secondary outcome [4] 0 0
The Number of Monthly Headache Days (MHD)
Timepoint [4] 0 0
Baseline to Week 24
Secondary outcome [5] 0 0
Number of Moderate to Severe MHD
Timepoint [5] 0 0
Baseline to Week 24
Secondary outcome [6] 0 0
Number of MHD Responders (Defined as a =50% Reduction in MHD)
Timepoint [6] 0 0
Baseline to Week 24
Secondary outcome [7] 0 0
Number of Moderate to Severe MHD Responders (Defined as a =50% Reduction in Moderate to Severe MHD)
Timepoint [7] 0 0
Baseline to Week 24
Secondary outcome [8] 0 0
Headache Severity
Timepoint [8] 0 0
Baseline to Week 24
Secondary outcome [9] 0 0
Use of Acute Headache Analgesic Medications (Acute Headache Analgesics in Days Per Month)
Timepoint [9] 0 0
Baseline to Week 24
Secondary outcome [10] 0 0
Visual Acuity
Timepoint [10] 0 0
Baseline to Week 24
Secondary outcome [11] 0 0
Number of Patients With Treatment Failure
Timepoint [11] 0 0
Baseline to Week 24

Eligibility
Key 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 magnetic resonance venography or computed tomographic venography to exclude thrombosis and no evidence of a secondary causes of raised ICP.
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 defined as between -2 to -7 decibels (dB) in at least one eye. 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) 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 25-140 IE/L and oestradiol <200 pmol/L is confirmatory]).
10. Male patients with a female partner of childbearing potential must commit to practice methods of contraception (e.g., condom, vasectomy) and abstain from sperm donation during 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 practice contraception 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
IIH-related 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.

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 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 uncertainty this would be evaluated by the IAC.

Headache-related exclusion criteria:
10. Does not complete =6 days of electronic/paper trial diary during the 7-day screening period.

Other exclusion criteria:
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. Using any glucose-lowering medication.
17. Currently taking warfarin.
18. 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).
19. Kidney disease (as defined by serum cystatin C-based estimated glomerular filtration rate <55 mL/min/1.73 m², calculated at investigator site).
20. 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: Haemoglobin <10 g/dL (<100 g/L); Platelet count <75 x 10?/L (<75,000/mm³).
21. Using recreational or illicit drugs at the time of signing the informed consent, or recent history (within the last year) of drug or alcohol abuse or dependence according to 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 trial medication with support) after receiving training during the screening period.
23. History of any clinically significant disease or disorder that, in the opinion of the investigator, may either put the patient at risk because of participation in the trial or 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 the screening visit.
26. Is pregnant or breastfeeding.

Note: Use of headache preventative medication is allowed at enrolment (except for topiramate). Changes to headache preventative medication during the trial should be made in consultation with the IAC.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/10/2023
Sample size
Target
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Sydney Eye Hospital - Sydney
Recruitment hospital [3] 0 0
Vision SA - Kent Town
Recruitment hospital [4] 0 0
Alfred Health - The Alfred Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2000 - Sydney
Recruitment postcode(s) [3] 0 0
5056 - Kent Town
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Germany
State/province [7] 0 0
Bonn
Country [8] 0 0
Germany
State/province [8] 0 0
Freiburg
Country [9] 0 0
Germany
State/province [9] 0 0
Mainz
Country [10] 0 0
Germany
State/province [10] 0 0
Münster
Country [11] 0 0
Israel
State/province [11] 0 0
Haifa
Country [12] 0 0
Israel
State/province [12] 0 0
Holon
Country [13] 0 0
Israel
State/province [13] 0 0
Jerusalem
Country [14] 0 0
Israel
State/province [14] 0 0
Tiberias
Country [15] 0 0
New Zealand
State/province [15] 0 0
Auckland
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Birmingham
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Invex Therapeutics Ltd.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Premier Research Group plc
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University Hospitals Birmingham Neuro Ophthalmology Reading Centre, Birmingham, UK
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Iowa Visual Field Reading Centre, Iowa, USA
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT05347147