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

Acanthamoeba Keratitis Clinical Trial

Official title:

Randomized, Active-Controlled, Phase 3 Study to Evaluate Efficacy, Safety and Tolerability of 0.08% PHMB Ophthalmic Solution in Comparison With 0.02% PHMB + 0.1% Propamidine Combination Therapy in Subjects Affected by Acanthamoeba Keratitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03274895
• Other study ID #: 043/SI
• Status: Completed
• Phase: Phase 3
• Start date: August 13, 2017
• Est. completion date: March 30, 2022

Study information

• Verified date: August 2023
• Source: SIFI SpA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

This was a randomized, assessor-masked, active-controlled, multiple center, parallel-group phase 3 study to evaluate the efficacy, safety and tolerability of 0.08% polihexanide (PHMB) ophthalmic solution compared to the conventional 0.02% polihexanide (PHMB) + 0.1% propamidine in patients affected by acanthamoeba keratitis.

The study was designed as a superiority study with the possibility to test for non-inferiority if the superiority hypothesis was not met (CPMP/EWP/482/99).The study consisted of an eligibility screening visit, a treatment period including monthly follow-up visits until a clinical resolution was obtained (within a maximum of 1 year), followed by 2 post-treatment off-therapy visits (30 and 90 days after treatment discontinuation). 130 subjects with confirmed diagnosis of acanthamoeba keratitis (clinical signs plus positive confocal microscopy findings) were assigned to one of the following treatment groups in a ratio of 1:1.

Group 1: 0.08% PHMB + placebo Group 2: 0.02% PHMB + 0.1% propamidine

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: March 30, 2022
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

Inclusion Criteria:

1. willing to give informed consent

2. man or woman of any race and =12 years of age

3. able to understand and willing to comply with study procedures, restrictions and requirements

4. Clinical findings consistent with Acanthamoeba keratitis

5. Confocal microscopy findings consistent with Acanthamoeba keratitis

6. The following previous treatments for Acanthamoeba keratitis are eligible:

antibiotics, antiviral and antifungal drugs, antiinflammatory drugs

7. Females of childbearing potential will be included if they are either sexually inactive or using one highly effective contraceptive

8. 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

9. A female of non-childbearing potential must have undergone one sterilization procedures at least 6 months prior to the first study drug dose

10. A non-vasectomized male subject agrees to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug and the female partner agrees to comply with inclusion 7 or 8. For a vasectomized male who has had his vasectomy 6 months or more prior to study start, it is required that they use a condom during sexual intercourse. A male who has been vasectomized less than 6 months prior to study start must follow the same restrictions as a non-vasectomized male.

11. If male, they must agree not to donate sperm from the first study drug dose until 90 days after dosing

Exclusion Criteria:

1. Subject with documented history and/or clinical signs of concomitant presence of an ocular infection caused by viruses (herpes simplex virus [HSV]) or fungi.

2. Subject treated with drugs having effects on Acanthamoeba cysts prior to study entry, including biguanides (PHMB, chlorhexidine) and diamidines (propamidine, hexamidine).

3. Subjects requiring systemic immunosuppression for Acanthamoeba associated scleritis.

4. Subjects requiring urgent surgical intervention for advanced Acanthamoeba keratitis in either eye (e.g., for advanced corneal thinning/melting etc.).

5. Subject with known or suspected allergy to biguanides, diamidines or intolerance to any other ingredient of the investigational treatments.

6. Subject affected by immunodeficiency diseases or taking systemic immunosuppressive therapy.

7. 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.

8. If female, pregnancy, planned pregnancy, or breast-feeding

9. 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.

Related Conditions & MeSH terms

• Acanthamoeba Keratitis
• Keratitis

Intervention

Drug:
• PHMB 0.08%
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
• Propamidine 0.1%
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
• placebo
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
• PHMB 0.02%
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

Locations

Country	Name	City	State
Italy	San Raffaele Hospital	Milano
Italy	San Giovanni and Paolo Hospital	Venice
Poland	University Clinical Center Medical University of Silesia	Katowice
United Kingdom	Moorfields Hospital	London
United Kingdom	Manchester Royal Eye Hospital	Manchester
United Kingdom	University Hospital Southampton	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
SIFI SpA

Countries where clinical trial is conducted

Italy,  Poland,  United Kingdom, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Resolution Rate	Percentage of patients cured 30 days after discontinuing all study therapies, within 12 months of randomization	12 months
Secondary	Time to Cure	Time needed to reach a clinical resolution	maximum 12 months
Secondary	Visual Acuity	Final visual acuity (best corrected)	maximum 12 months