Polihexanide (PHMB) Eye Drops in Patients Affected by Acanthamoeba Keratitis

NCT03274895 | Completed Phase 3 Results

• 1 other identifier: 043/SI
• Study Type: interventional
• Target: 135
• Locations: 3 countries
• Sites: 6

Brief Summary

Prospective randomized study to evaluate the efficacy, safety and tolerability of 0.08% polihexanide (PHMB) eye drops in patients affected by acanthamoeba keratitis. 130 subjects were assigned to one of the following 2 treatment groups: Group 1: 0.08% polihexanide (PHMB) + placebo Group 2: 0.02% polihexanide (PHMB) + 0.1% propamidine

Conditions

Acanthamoeba Keratitis

Keywords

polihexanide; propamidine; confocal microscopy

Outcome Measures

Primary Outcomes (1)

• Clinical Resolution Rate

  Percentage of patients cured 30 days after discontinuing all study therapies, within 12 months of randomization

  12 months

Secondary Outcomes (2)

• Time to Cure

  maximum 12 months

• Visual Acuity

  maximum 12 months

Study Arms (2)

PHMB 0.08% plus placebo

EXPERIMENTAL

polihexanide (PHMB) 0.08% and placebo were administered in the affected eye until clinical resolution for a maximum of 12 months

Drug: PHMB 0.08%; Drug: placebo

PHMB 0.02% plus propamidine 0.1%

ACTIVE COMPARATOR

polihexanide (PHMB) 0.02% and propamidine 0.1% were administered in the affected eye until clinical resolution for a maximum of 12 months

Drug: Propamidine 0.1%; Drug: PHMB 0.02%

Interventions

PHMB 0.08% DRUG

16 drops in a day in the affected eye for 5 days followed by 8 drops in a day for 7 days,6 drops in a day for 7 days and 4 drops in a day up to clinical resolution

Also known as: Polihexanide 0.8 mg/ml

PHMB 0.08% plus placebo

Propamidine 0.1% DRUG

16 drops in a day in the affected eye for 5 days followed by 8 drops in a day for 7 days,6 drops in a day for 7 days and 4 drops in a day up to clinical resolution

Also known as: Brolene eye drops

PHMB 0.02% plus propamidine 0.1%

placebo DRUG

16 drops in a day in the affected eye for 5 days followed by 8 drops in a day for 7 days,6 drops in a day for 7 days and 4 drops in a day up to clinical resolution

Also known as: Brolene vehicle

PHMB 0.08% plus placebo

PHMB 0.02% DRUG

16 drops in a day in the affected eye for 5 days followed by 8 drops in a day for 7 days,6 drops in a day for 7 days and 4 drops in a day up to clinical resolution

Also known as: Polihexanide 0.2 mg/ml

PHMB 0.02% plus propamidine 0.1%

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• willing to give informed consent
• man or woman of any race and ≥12 years of age
• able to understand and willing to comply with study procedures, restrictions and requirements
• Clinical findings consistent with Acanthamoeba keratitis
• Confocal microscopy findings consistent with Acanthamoeba keratitis
• The following previous treatments for Acanthamoeba keratitis are eligible: antibiotics, antiviral and antifungal drugs, antiinflammatory drugs
• Females of childbearing potential will be included if they are either sexually inactive or using one highly effective contraceptive
• Females of childbearing potential agree to remain sexually inactive or to keep the same birth control method for at least 28 days following the last study drug dose
• A female of non-childbearing potential must have undergone one sterilization procedures at least 6 months prior to the first study drug dose
• If male, they must agree not to donate sperm from the first study drug dose until 90 days after dosing

You may not qualify if:

• Subject with documented history and/or clinical signs of concomitant presence of an ocular infection caused by viruses (herpes simplex virus \[HSV\]) or fungi.
• Subject treated with drugs having effects on Acanthamoeba cysts prior to study entry, including biguanides (PHMB, chlorhexidine) and diamidines (propamidine, hexamidine).
• Subjects requiring systemic immunosuppression for Acanthamoeba associated scleritis.
• Subjects requiring urgent surgical intervention for advanced Acanthamoeba keratitis in either eye (e.g., for advanced corneal thinning/melting etc.).
• Subject with known or suspected allergy to biguanides, diamidines or intolerance to any other ingredient of the investigational treatments.
• Subject affected by immunodeficiency diseases or taking systemic immunosuppressive therapy.
• Subject with a major systemic disease or other illness that would, in the opinion of the investigator, compromise subject's safety or interfere with the collection or interpretation of study results.
• If female, pregnancy, planned pregnancy, or breast-feeding
• Subject is participating in another interventional clinical study with an experimental or unapproved/unlicensed therapy or has participated in another interventional clinical study within 4 weeks prior to this study.

Sponsors & Collaborators

• SIFI SpA: lead

Study Sites (6)

San Raffaele Hospital

Milan, Italy

Location

San Giovanni and Paolo Hospital

Venice, Italy

Location

University Clinical Center Medical University of Silesia

Katowice, Poland

Location

Moorfields Hospital

London, United Kingdom

Location

Manchester Royal Eye Hospital

Manchester, United Kingdom

Location

University Hospital Southampton

Southampton, United Kingdom

Location

Related Publications (3)

• Papa V, Rama P, Radford C, Minassian DC, Dart JKG. Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases. Br J Ophthalmol. 2020 Apr;104(4):575-581. doi: 10.1136/bjophthalmol-2019-314485. Epub 2019 Aug 10.

  PMID: 31401556 BACKGROUND

• Papa V, van der Meulen I, Rottey S, Sallet G, Overweel J, Asero N, Minassian DC, Dart JKG. Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers. Br J Ophthalmol. 2022 Feb;106(2):190-196. doi: 10.1136/bjophthalmol-2020-317848. Epub 2020 Nov 25.

  PMID: 33239413 BACKGROUND

• Dart JKG, Papa V, Rama P, Knutsson KA, Ahmad S, Hau S, Sanchez S, Franch A, Birattari F, Leon P, Fasolo A, Kominek EM, Jadczyk-Sorek K, Carley F, Hossain P, Minassian DC. The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1. Ophthalmology. 2024 Mar;131(3):277-287. doi: 10.1016/j.ophtha.2023.09.031. Epub 2023 Oct 5.

  PMID: 37802392 DERIVED

MeSH Terms

Conditions

Acanthamoeba Keratitis

Interventions

polihexanide; dibrompropamidine

Condition Hierarchy (Ancestors)

Eye Infections, Parasitic; Parasitic Diseases; Infections; Amebiasis; Protozoan Infections; Keratitis; Corneal Diseases; Eye Diseases; Eye Infections

Results Point of Contact

• Title: Dr. Jelle Kleijn
• Organization: SIFI SpA

jelle.kleijn@sifigroup.com

+31615643708

Study Officials

• John Dart, MD

  Moorfield's Hospital London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 7, 2017
• Study Start: August 13, 2017
• Primary Completion: June 30, 2021
• Study Completion: March 30, 2022
• Last Updated: August 22, 2023
• Results First Posted: August 2, 2023

Record last verified: 2023-08

Locations

IT (2); GB (3); PL (1)