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

August 2, 2023 updated by: SIFI SpA

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Actual)

135

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PHMB 0.08% plus placebo
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%
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
Other Names:
  • Polihexanide 0.8 mg/ml
Drug: 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
Other Names:
  • Brolene vehicle
Active Comparator: PHMB 0.02% plus propamidine 0.1%
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%
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
Other Names:
  • Brolene eye drops
Drug: 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
Other Names:
  • Polihexanide 0.2 mg/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Resolution Rate
Time Frame: 12 months
Percentage of patients cured 30 days after discontinuing all study therapies, within 12 months of randomization
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Cure
Time Frame: maximum 12 months
Time needed to reach a clinical resolution
maximum 12 months
Visual Acuity
Time Frame: maximum 12 months
Final visual acuity (best corrected)
maximum 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SIFI SpA

Investigators

  • Principal Investigator: John Dart, MD, Moorfield's Hospital London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 13, 2017

Primary Completion (Actual)

June 30, 2021

Study Completion (Actual)

March 30, 2022

Study Registration Dates

First Submitted

September 5, 2017

First Submitted That Met QC Criteria

September 5, 2017

First Posted (Actual)

September 7, 2017

Study Record Updates

Last Update Posted (Actual)

August 22, 2023

Last Update Submitted That Met QC Criteria

August 2, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 043/SI

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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