Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
MY TRIALS
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Register a trial
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
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
Query!
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
Query!
Secondary ID [1]
0
0
INVEX-CLIN-IIH-301
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
IIH EVOLVE
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Idiopathic Intracranial Hypertension
0
0
Query!
Condition category
Condition code
Neurological
0
0
0
0
Query!
Other neurological disorders
Query!
Cardiovascular
0
0
0
0
Query!
Hypertension
Query!
Intervention/exposure
Study type
Interventional
Query!
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.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
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
Query!
Assessment method [1]
0
0
ICP was measured by LP (opening pressure) using an LP manometer; Baseline and Week 24 ICP values (measured in cm CSF) are presented for each subject. A standard operating procedure was followed by all study sites for all study-related ICP measurements by LP.
Query!
Timepoint [1]
0
0
Baseline to Week 24
Query!
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
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
Baseline to Week 24
Query!
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
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
Baseline to Week 24
Query!
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
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
Baseline to Week 24
Query!
Secondary outcome [4]
0
0
The Number of Monthly Headache Days (MHD)
Query!
Assessment method [4]
0
0
Monthly headache days (according to daily headache diary) = number of days recorded in a 28-day window where data were collected on \>7 days and where =1 headache on a day met the following criteria:
* Onset, continuation, or recurrence of headache
* Any severity or phenotype of headache
* Lasts at least 30 minutes
Baseline headache frequency was calculated over the 7 days prior to the randomization visit; =5 days of headache data were needed to obtain a valid baseline value. The number of headache days recorded for a period were linearly scaled by the total number of days of data collected in the period for each subject to give the MHD during the baseline period (linearly scaled to a maximum of 28 days) and the last 28-day period during which data were collected on \>7 days for each subject prior to study completion or discontinuation.
Period 1 = Weeks 1-4 Period 2 = Weeks 5-8 Period 3 = Weeks 9-12 Period 4 = Weeks 13-16 Period 5 = Weeks 17-20 Period 6 = Weeks 21-24
Query!
Timepoint [4]
0
0
Baseline to Week 24
Query!
Secondary outcome [5]
0
0
Number of Moderate to Severe MHD
Query!
Assessment method [5]
0
0
Moderate to severe (m-s) MHD (according to daily headache diary) = number of days recorded in a 28-day window where data were collected on \>7 days and where =1 headache on a day met the following criteria:
* Severity was of moderate or severe pain and lasted at least 4 hours or,
* Required acute headache analgesics
Baseline m-s headache frequency was calculated over the 7 days prior to the randomization visit; =5 days of headache data were needed to obtain a valid baseline value. The number of m-s headache days recorded for a period were linearly scaled by the total number of days of data collected in the period for each subject to give the m-s MHD during the baseline period (linearly scaled to a max 28 days) and the last 28-day period during which data were collected on \>7 days for each subject prior to study completion or discontinuation.
Period 1 = Weeks 1-4 Period 2 = Weeks 5-8 Period 3 = Weeks 9-12 Period 4 = Weeks 13-16 Period 5 = Weeks 17-20 Period 6 = Weeks 21-24
Query!
Timepoint [5]
0
0
Baseline to Week 24
Query!
Secondary outcome [6]
0
0
Number of MHD Responders (Defined as a =50% Reduction in MHD)
Query!
Assessment method [6]
0
0
A subject was considered a responder if they had at least a 50% reduction in MHD from baseline to Week 24. Subjects who dropped out prior to Week 24 were considered non-responders.
Query!
Timepoint [6]
0
0
Baseline to Week 24
Query!
Secondary outcome [7]
0
0
Number of Moderate to Severe MHD Responders (Defined as a =50% Reduction in Moderate to Severe MHD)
Query!
Assessment method [7]
0
0
A subject was considered a responder if they had at least a 50% reduction in moderate to severe MHD from baseline to Week 24. Subjects who dropped out prior to Week 24 were considered non-responders.
Query!
Timepoint [7]
0
0
Baseline to Week 24
Query!
Secondary outcome [8]
0
0
Headache Severity
Query!
Assessment method [8]
0
0
Headache severity was assessed by a 10-point Numeric Rating Scale (NRS), 0-10 where 0 = no pain and 10 = most severe pain. Severity of headaches was assessed on days where a headache occurred. Headache free days were not counted. Baseline headache severity was calculated over the 7 days prior to the randomization visit; at least 5 of 7 days of headache severity data had to be recorded by the subject to obtain a valid baseline value.
* 28-day period 1 = Weeks 1-4
* 28-day period 2 = Weeks 5-8
* 28-day period 3 = Weeks 9-12
* 28-day period 4 = Weeks 13-16
* 28-day period 5 = Weeks 17-20
* 28-day period 6 = Weeks 21-24
Query!
Timepoint [8]
0
0
Baseline to Week 24
Query!
Secondary outcome [9]
0
0
Use of Acute Headache Analgesic Medications (Acute Headache Analgesics in Days Per Month)
Query!
Assessment method [9]
0
0
Number of days recorded in a 28-day window, where at least one dose of an acute headache analgesic was recorded.
The baseline acute headache analgesic use was calculated over the 7 days prior to the randomization visit; at least 5 of 7 days had to be recorded by the subject to obtain a valid baseline value.
The number of acute headache analgesic use days was linearly scaled for each subject to give the number of acute headache analgesic use days during the baseline period and the last 28-day period during which headache data were collected on more than 7 days for each subject prior to study completion or discontinuation.
* 28-day period 1 = Weeks 1-4
* 28-day period 2 = Weeks 5-8
* 28-day period 3 = Weeks 9-12
* 28-day period 4 = Weeks 13-16
* 28-day period 5 = Weeks 17-20
* 28-day period 6 = Weeks 21-24
Query!
Timepoint [9]
0
0
Baseline to Week 24
Query!
Secondary outcome [10]
0
0
Visual Acuity
Query!
Assessment method [10]
0
0
Corrected visual acuity will be recorded using a Logarithm of the Minimum Angle of Resolution (LogMAR) scoring chart, with a range of -0.3 to 1.00, where a lower score indicates better visual acuity.
Query!
Timepoint [10]
0
0
Baseline to Week 24
Query!
Secondary outcome [11]
0
0
Number of Patients With Treatment Failure
Query!
Assessment method [11]
0
0
Treatment failure is defined as the initiation of either medical therapy or a surgical intervention to lower ICP during the study.
Query!
Timepoint [11]
0
0
Baseline to Week 24
Query!
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.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
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
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Stopped early
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
18/11/2022
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
20/10/2023
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
14
Query!
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Query!
Recruitment hospital [1]
0
0
Liverpool Hospital - Liverpool
Query!
Recruitment hospital [2]
0
0
Sydney Eye Hospital - Sydney
Query!
Recruitment hospital [3]
0
0
Vision SA - Kent Town
Query!
Recruitment hospital [4]
0
0
Alfred Health - The Alfred Centre - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
2170 - Liverpool
Query!
Recruitment postcode(s) [2]
0
0
2000 - Sydney
Query!
Recruitment postcode(s) [3]
0
0
5056 - Kent Town
Query!
Recruitment postcode(s) [4]
0
0
3004 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Colorado
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Florida
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Minnesota
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
New York
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Tennessee
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Texas
Query!
Country [7]
0
0
Germany
Query!
State/province [7]
0
0
Bonn
Query!
Country [8]
0
0
Germany
Query!
State/province [8]
0
0
Freiburg
Query!
Country [9]
0
0
Germany
Query!
State/province [9]
0
0
Mainz
Query!
Country [10]
0
0
Germany
Query!
State/province [10]
0
0
Münster
Query!
Country [11]
0
0
Israel
Query!
State/province [11]
0
0
Haifa
Query!
Country [12]
0
0
Israel
Query!
State/province [12]
0
0
Holon
Query!
Country [13]
0
0
Israel
Query!
State/province [13]
0
0
Jerusalem
Query!
Country [14]
0
0
Israel
Query!
State/province [14]
0
0
Tiberias
Query!
Country [15]
0
0
New Zealand
Query!
State/province [15]
0
0
Auckland
Query!
Country [16]
0
0
United Kingdom
Query!
State/province [16]
0
0
Birmingham
Query!
Country [17]
0
0
United Kingdom
Query!
State/province [17]
0
0
London
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Invex Therapeutics Ltd.
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/industry
Query!
Name [1]
0
0
Premier Research Group plc
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Other collaborator category [2]
0
0
Other
Query!
Name [2]
0
0
University Hospitals Birmingham Neuro Ophthalmology Reading Centre, Birmingham, UK
Query!
Address [2]
0
0
Query!
Country [2]
0
0
Query!
Other collaborator category [3]
0
0
Other
Query!
Name [3]
0
0
Iowa Visual Field Reading Centre, Iowa, USA
Query!
Address [3]
0
0
Query!
Country [3]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
Idiopathic intracranial hypertension (IIH) has significant associated morbidity and reduced quality of life. There is a significant risk of visual loss and patients also typically suffer with chronic disabling headaches. This trial has been designed to evaluate the efficacy and safety of a new formulation of exenatide (Presendin) in the reduction of intracranial pressure (ICP) in patients with IIH.
Query!
Trial website
https://clinicaltrials.gov/study/NCT05347147
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/47/NCT05347147/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/47/NCT05347147/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT05347147