Presendin for Pseudotumor Cerebri

(IIH EVOLVE Trial)

No longer recruiting at 24 trial locations

Overseen By Alexandra J Sinclair, MBChB, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Invex Therapeutics Ltd.

Must not be taking: Glucose-lowering, Warfarin, Topiramate, others

Disqualifiers: Venous thrombosis, IIH surgery, Kidney disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, Presendin, to determine if it can safely and effectively lower intracranial pressure in individuals with idiopathic intracranial hypertension (IIH). IIH can cause severe headaches and vision problems, so the trial aims to improve these symptoms. Participants will receive either Presendin or a placebo (a non-active substance) to compare effects. Those recently diagnosed with IIH and experiencing frequent headaches may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participation. You must stop taking any treatments to lower intracranial pressure (like acetazolamide or topiramate) at least one week before the screening. Additionally, you cannot use any glucose-lowering medications or be currently taking warfarin.

Is there any evidence suggesting that Presendin is likely to be safe for humans?

Research shows that Presendin, a new version of the drug exenatide, has undergone safety testing in people. In previous studies, patients generally tolerated the treatment well, with few experiencing serious side effects. Common side effects might include mild nausea or dizziness, but these are usually not severe. The trial's advanced stage suggests that earlier studies found Presendin safe enough for further testing. As always, discussing any concerns with a healthcare provider before joining a trial is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike current treatments for Idiopathic Intracranial Hypertension (IIH), which often include weight loss, diuretics, or surgical interventions, Presendin offers a novel approach by using a new active ingredient. Presendin is unique because it works through an innovative mechanism that targets specific pathways believed to be involved in IIH, potentially offering a more direct and effective treatment option. Researchers are excited about Presendin because it has the potential to provide relief with fewer side effects compared to the standard treatments, improving the quality of life for patients.

What evidence suggests that Presendin might be an effective treatment for IIH?

Research has shown that exenatide, the main ingredient in Presendin, might help lower skull pressure in people with idiopathic intracranial hypertension (IIH). Studies have found that this drug can reduce the risk of papilledema, a swelling of the optic nerve that can cause vision problems. This suggests that Presendin, which participants in this trial may receive, might alleviate symptoms like headaches and vision issues linked to IIH. The drug aims to lower brain pressure, a major issue in IIH. While more research is needed, early results are promising for its effectiveness in managing this condition. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

Inclusion Criteria

Able to provide written informed consent.

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).

Exclusion Criteria

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.

Does not complete ≥6 days of electronic/paper trial diary during the 7-day screening period.

COVID-19 vaccine within 2 weeks prior to screening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive a subcutaneous dose of either Presendin or placebo, self-administered once weekly

24 weeks

Weekly self-administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 weeks

1 telephone visit

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Presendin

How Is the Trial Designed?

Group I: Presendin Experimental Treatment 1 Intervention

2.0 mg

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Invex Therapeutics Ltd.

Lead Sponsor

Trials

1

Recruited

10+

University Hospitals Birmingham Neuro Ophthalmology Reading Centre, Birmingham, UK

Collaborator

Trials

1

Recruited

10+

Iowa Visual Field Reading Centre, Iowa, USA

Collaborator

Trials

1

Recruited

10+

Premier Research

Collaborator

Premier Research Group plc

Collaborator

University Hospital Birmingham

Collaborator

Trials

61

Recruited

45,700+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

Premier Research Group plc

Industry Sponsor

Trials

65

Recruited

74,200+

John Ratliff

Premier Research Group plc

Chief Executive Officer since 2024

MBA

Dr. Milena Kanova-Petrova

Premier Research Group plc

Chief Medical Officer since 2024

MD

Published Research Related to This Trial

Randomized two-arm clinical trials comparing an active drug to a placebo are the best way to show a new treatment's efficacy, but statistical significance alone isn't enough; clinical relevance must also be assessed.

Including an active control group in a three-arm study design can help define what constitutes a clinically relevant difference in efficacy, addressing the challenge of demonstrating both statistical and clinical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishing efficacy of a new experimental treatment in the 'gold standard' design. Hauschke, D., Pigeot, I.[2019]

In a randomized, double-blind clinical trial involving 125 patients with referred shoulder pain, applying a force to the C5 vertebra using a mechanically assisted instrument (MAI) significantly improved internal rotation strength after 6 months (P = 0.04).

While the treatment cohort experienced a reduction in the frequency of extreme shoulder pain (from weekly to monthly), there was no significant change in the severity of pain or other functional outcomes compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Assessing the Effects of Applying a Force to C5 by a Mechanically Assisted Instrument on Referred Pain to the Shoulder. Hardas, GM., Murrell, GAC.[2021]

The C1-C2 self-sustained natural apophyseal glide (SNAG) technique significantly improved the range of motion in the cervical spine by 15 degrees in participants with cervicogenic headaches, compared to only 5 degrees in the placebo group, indicating its effectiveness in addressing C1-C2 dysfunction.

Participants using the C1-C2 self-SNAG reported a substantial reduction in headache symptoms, with scores decreasing by 54% over 12 months, demonstrating its long-term efficacy in managing cervicogenic headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a C1-C2 self-sustained natural apophyseal glide (SNAG) in the management of cervicogenic headache. Hall, T., Chan, HT., Christensen, L., et al.[2022]

The mouthrinse containing 0.05% CHX and 0.05% CPC significantly reduced plaque levels in patients with poor oral hygiene over a 3-month period, indicating its efficacy in improving oral health (P<0.001).

While the mouthrinse effectively decreased plaque and bleeding on probing, it did not show a significant impact on gingival inflammation or overall patient-reported outcomes, suggesting that while it helps with plaque control, it may not fully address all aspects of gum health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower concentration of chlorhexidine and cetyl-pyridinium chloride mouthwash demonstrates some efficacy. Lamont, T.[2012]

In a clinical trial with 73 participants suffering from rotator cuff related shoulder pain, omega-3 polyunsaturated fatty acids (PUFAs) showed a modest improvement in pain and disability outcomes, particularly noted in the Shoulder Pain and Disability Index (SPADI) at 3 months.

However, there was no significant difference in the primary outcome, the Oxford Shoulder Score (OSS), between the omega-3 group and the placebo group at the 2-month mark, indicating that while there may be some benefits, they are not robust.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised controlled trial of long-chain omega-3 polyunsaturated fatty acids in the management of rotator cuff related shoulder pain. Sandford, FM., Sanders, TA., Wilson, H., et al.[2022]

Exenatide is an effective treatment for type 2 diabetes that helps lower blood sugar levels and HbA1c without causing hypoglycemia or requiring regular blood glucose monitoring, making it a convenient option for patients.

It not only stimulates insulin secretion and inhibits glucagon but also promotes weight loss and slows gastric emptying, which can be particularly beneficial for overweight or obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medication of the month... Exenatide (Byetta) incretinomimetic in the treatment of type 2 diabetes after failure and as add-on therapy to oral agents]. Scheen, AJ., Van Gaal, LF.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05347147

A Trial to Determine the Efficacy and Safety of Presendin ... 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) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12426903/

Efficacy and Safety of GLP‐1 and Dual GIP ... An aggregate data meta‐analysis was performed including all identified studies. The primary efficacy outcomes were the risk of (i) papilledema; ...

3. ctv.veeva.com ctv.veeva.com/study/a-trial-to-determine-the-efficacy-and-safety-of-presendin-in-iih

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

4. withpower.com withpower.com/trial/phase-3-intracranial-hypertension-5-2022-5b5f9

A Trial to Determine the Efficacy and Safety of Presendin ... The trial requires stopping certain medications before participation. You must stop taking any treatments to lower intracranial pressure (like acetazolamide ...

5. smallcaps.com.au smallcaps.com.au/article/invex-therapeutics-recruits-first-idiopathic-intracranial-hypertension-patient-presendin-trial

Invex Therapeutics recruits first idiopathic intracranial ... The primary endpoint of the trial is a change in intracranial pressure from baseline, with key secondary endpoints related to vision and headache outcome ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05347147?term=AREA%5BConditionSearch%5D(%22Idiopathic%20Intracranial%20Hypertension%22)&rank=8

A Trial to Determine the Efficacy and Safety of Presendin ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

7. delta.larvol.com delta.larvol.com/Products/?ProductId=52ba49d2-c643-4bfd-b64c-aac845021f4f

Presendin (exenatide sustained release) / Invex Therap IIH EVOLVE: A Trial to Determine the Efficacy and Safety of Presendin in IIH ... This data provides confidence to proceed to a phase 3 trial in idiopathic ...