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

(IIH EVOLVE Trial)

Recruiting at 23 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

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new injectable drug called Presendin to help patients with high skull pressure due to IIH. The drug aims to reduce brain fluid pressure, which may relieve headaches and protect vision.

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.

What data supports the effectiveness of the drug Presendin?

The research on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like efpeglenatide and lixisenatide shows they can help control blood sugar levels in people with type 2 diabetes, suggesting that similar drugs like Presendin might also be effective for managing this condition. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Exenatide, a treatment for type 2 diabetes, is generally safe and does not directly cause low blood sugar (hypoglycemia) or require constant blood sugar monitoring. It may cause weight loss and slow stomach emptying, but nausea is less common after starting treatment. ^{6 7 8 9 10}

How does the drug Presendin differ from other treatments for this condition?

Presendin is being tested in a placebo-controlled clinical trial, which is considered the 'gold standard' for demonstrating the effectiveness of a new treatment. This approach helps ensure that any observed benefits are truly due to the drug itself and not other factors. ^{11 12 13 14 15}

Eligibility Criteria

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

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

Treatment Details

Interventions

• Placebo
• Presendin

Participant Groups

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+

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

Findings from Research

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]

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]

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 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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Addition of dipeptidyl peptidase-4 inhibitors to insulin treatment in type 2 diabetes patients: A meta-analysis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effects of sequential treatment with lixisenatide, insulin glargine, or their combination on meal-related glycaemic excursions, insulin and glucagon secretion, and gastric emptying in patients with type 2 diabetes. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Once-Weekly Efpeglenatide Monotherapy Versus Placebo in Type 2 Diabetes: The AMPLITUDE-M Randomized Controlled Trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Lixisenatide Therapy in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Antidiabetic Treatment: The GetGoal-O Randomized Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A propensity score matched comparison of different insulin regimens 1 year after beginning insulin in people with type 2 diabetes. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacodynamics of NN2211, a novel long acting GLP-1 derivative. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Exploring the Possible Impact of Unbalanced Open-Label Drop-In of Glucose-Lowering Medications on EXSCEL Outcomes. [2021]

9. Belgium 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]. [2018]

10. France pubmed.ncbi.nlm.nih.gov

Insulin treatment with preprandial injections of regular insulin in middle-aged type 2 diabetic patients. A two years observational study. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Establishing efficacy of a new experimental treatment in the 'gold standard' design. [2019]

12. England pubmed.ncbi.nlm.nih.gov

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

13. United States 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. [2021]

14. England 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. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

Efficacy of a C1-C2 self-sustained natural apophyseal glide (SNAG) in the management of cervicogenic headache. [2022]