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

NCT05347147 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: INVEX-CLIN-IIH-301
• Study Type: interventional
• Target: 14
• Locations: 6 countries
• Sites: 24

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.

Conditions

Idiopathic Intracranial Hypertension

Keywords

Presendin

Outcome Measures

Primary Outcomes (1)

• Change in ICP From Baseline to Week 24 Measured by Lumbar Puncture (LP), Where a Higher LP Value Indicates Greater ICP

  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.

  Baseline to Week 24

Secondary Outcomes (11)

• 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

  Baseline to Week 24

• Papilloedema by Change in Retinal Nerve Fibre Layer (RNFL) Thickness, With a Greater Thickness of RNFL Indicating Greater Swelling and Greater Extent of Papilloedema

  Baseline to Week 24

• 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

  Baseline to Week 24

• The Number of Monthly Headache Days (MHD)

  Baseline to Week 24

• Number of Moderate to Severe MHD

  Baseline to Week 24

Study Arms (2)

Presendin

EXPERIMENTAL

2.0 mg

Drug: Presendin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Presendin DRUG

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.

Presendin

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of consent.
• 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.
• Newly diagnosed patients with screening commenced no more than 4 weeks after the diagnostic LP.
• Lumbar puncture opening pressure ≥25 cm cerebrospinal fluid (CSF) at diagnosis.
• 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).
• 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'.
• 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.
• 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.
• 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 \[in questionable cases a blood sample with simultaneous follicle stimulation hormone 25-140 IE/L and oestradiol \<200 pmol/L is confirmatory\]).
• 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).
• Able to provide written informed consent.

You may not qualify if:

• Presence of venous sinus thrombosis on brain imaging by either magnetic resonance or computerised tomographic venography.
• Previous IIH surgery including CSF shunt, optic nerve sheath fenestration or dural venous sinus stent or sub-temporal decompression.
• Previous bariatric surgery within the last 3 months or intention during the trial.
• Abnormal neurological examination (aside from papilloedema and consequent visual loss or sixth or seventh nerve palsy or palsies).
• 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.
• 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.
• 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.
• 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.
• 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.
• Does not complete ≥6 days of electronic/paper trial diary during the 7-day screening period.
• Untreated previously diagnosed obstructive sleep apnoea with historically recorded apnoea-hypopnea index greater than 15.
• Glucagon like peptide-1 receptor agonist within last 4 weeks prior to screening.
• COVID-19 vaccine within 2 weeks prior to screening.
• Allergy/known hypersensitivity to the active substance and/or excipients of the investigational product.
• 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.

Sponsors & Collaborators

• Invex Therapeutics Ltd.: lead
• Premier Research: collaborator
• University Hospital Birmingham: collaborator
• University of Iowa: collaborator

Study Sites (24)

UCHealth Sue Anschutz-Rodgers Eye Center - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Miami Leonard M. Miller School of Medicine (UMMSM) - Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

University of Minnesota Health

Minneapolis, Minnesota, 55455, United States

Location

New York Eye and Ear Infirmary of Mount Sinai

New York, New York, 10075, United States

Location

Vanderbilt Eye Institute

Nashville, Tennessee, 37232, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Neuro-Eye Clinical Trials, Inc

Houston, Texas, 77074, United States

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Sydney Eye Hospital

Sydney, New South Wales, 2000, Australia

Location

Vision SA

Kent Town, South Australia, 5056, Australia

Location

Alfred Health - The Alfred Centre

Melbourne, Victoria, 3004, Australia

Location

University Hospital Bonn

Bonn, 53105, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitaetsmedizin Mainz

Mainz, 55131, Germany

Location

University Hospital Muenster, Department Ophthalmology Clinical Trials in Ophthalmology (CTO)

Münster, 48149, Germany

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Bnai Zion Medical Center

Haifa, 3339419, Israel

Location

The Edith Wolfson Medical Center

Holon, 5822012, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center - Ein Karem

Jerusalem, 91120, Israel

Location

Pade Medical Center (Poriya)

Tiberias, 1528001, Israel

Location

New Zealand Clinical Research (Aukland)

Auckland, 0624, New Zealand

Location

University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham

Birmingham, B15 2GW, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

MeSH Terms

Conditions

Pseudotumor Cerebri

Condition Hierarchy (Ancestors)

Intracranial Hypertension; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Due to the early termination of the study, planned analyses were not fully conducted but were restricted to the most relevant safety endpoints as per the abbreviated SAP v1. Outcome measure (efficacy) data are raw data from individual subjects, with minimal analysis; e.g., where an outcome measure specified change from baseline to Week 24, baseline and Week 24 values are presented. Efficacy data were not subject to the same verification as safety data and no efficacy conclusions should be drawn.

Results Point of Contact

• Title: Tom Duthy
• Organization: Executive Director Invex Australia

tduthy@invextherapeutics.com

+61 (08) 6382 0137

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigators and other site personnel, patients, contract research organisation and Sponsor personnel will be blinded regarding the treatment during the randomised period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This will be a placebo-controlled, double-blind, multi-centre clinical trial in approximately 240 randomised patients with IIH.

Study Record Dates

• First Submitted: April 20, 2022
• First Posted: April 26, 2022
• Study Start: November 18, 2022
• Primary Completion: September 18, 2023
• Study Completion: October 20, 2023
• Last Updated: April 24, 2024
• Results First Posted: April 24, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); AU (4); IL (6); NZ (1); US (7); DE (4)