Title

Polyhexamethylene Biguanide (PHMB) Ophthalmic Solution in Subjects Affected by Acanthamoeba Keratitis
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
  • Phase

    Phase 3
  • Study Type

    Interventional
  • Status

    Unknown status
  • Study Participants

    130
Phase 3 study to evaluate the efficacy, safety and tolerability of 0.08% PHMB ophthalmic solution in subjects affected by Acanthamoeba keratitis.

A total of 130 subjects will be assigned to one of the following 2 treatment groups:

Group 1: 0.08% PHMB + placebo Group 2: 0.02% PHMB + 0.1% propamidine combination therapy
This is a randomized, assessor-masked, active-controlled, multiple center, parallel-group Phase 3 study to evaluate the efficacy, safety and tolerability of 0.08% PHMB ophthalmic solution compared to the conventional 0.02% PHMB + 0.1% propamidine combination therapy in male and female subjects affected by Acanthamoeba keratitis.

The study is designed as a superiority study with the possibility to test for non-inferiority if the superiority hypothesis is not met, according to the requirements of the guidance from the European Agency for the Evaluation of Medicinal Products (EMA) (CPMP/EWP/482/99).The study consists of an eligibility screening visit, a treatment period including short ambulant visits, and follow-up visits. A total of approximately 130 subjects affected by Acanthamoeba keratitis will be assigned to one of the following 2 treatment groups in a ratio of 1:1.

Group 1: 0.08% PHMB + placebo Group 2: 0.02% PHMB + 0.1% propamidine combination therapy
Study Started
Aug 13
2017
Primary Completion
Jun 30
2021
Anticipated
Study Completion
Sep 30
2021
Anticipated
Last Update
Oct 23
2020

Drug PHMB 0.08%

16 drops in a day for 5 days,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: Polyhexamethylene Biguanide 0.08%

Drug Propamidine 0.1%

16 drops in a day for 5 days,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 placebo

16 drops in a day for 5 days,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

Drug PHMB 0.02%

16 drops in a day for 5 days,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: Polyhexamethylene Biguanide 0.02%

PHMB 0.08% plus placebo Experimental

16 drops each in a day for 5 days,8 drops each in a day for 7 days,6 drops each in a day for 7 days and 4 drops each in a day up to clinical resolution

PPHMB 0.02% plus propamidine 0.1% Active Comparator

16 drops each in a day for 5 days,8 drops each in a day for 7 days,6 drops each in a day for 7 days and 4 drops each in a day up to clinical resolution

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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.
No Results Posted