Polyhexamethylene Biguanide (PHMB) Ophthalmic Solution in Subjects Affected by Acanthamoeba Keratitis
Study Details
Study Description
Brief Summary
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
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Detailed Description
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: PHMB 0.08% plus placebo 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 |
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:
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:
|
Active Comparator: PPHMB 0.02% plus propamidine 0.1% 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 |
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:
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:
|
Outcome Measures
Primary Outcome Measures
- Clinical resolution rate [12 months]
Percentage of patients cured 30 days after discontinuing all study therapies, within 12 months of randomization
Eligibility Criteria
Criteria
Inclusion Criteria:
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willing to give informed consent
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man or woman of any race and ≥12 years of age
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able to understand and willing to comply with study procedures, restrictions and requirements
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Clinical findings consistent with Acanthamoeba keratitis
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Confocal microscopy findings consistent with Acanthamoeba keratitis
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The following previous treatments for Acanthamoeba keratitis are eligible: antibiotics, antiviral and antifungal drugs, antiinflammatory drugs
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Females of childbearing potential will be included if they are either sexually inactive or using one highly effective contraceptive
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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
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A female of non-childbearing potential must have undergone one sterilization procedures at least 6 months prior to the first study drug dose
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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.
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If male, they must agree not to donate sperm from the first study drug dose until 90 days after dosing
Exclusion Criteria:
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Subject with documented history and/or clinical signs of concomitant presence of an ocular infection caused by viruses (herpes simplex virus [HSV]) or fungi.
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Subject treated with drugs having effects on Acanthamoeba cysts prior to study entry, including biguanides (PHMB, chlorhexidine) and diamidines (propamidine, hexamidine).
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Subjects requiring systemic immunosuppression for Acanthamoeba associated scleritis.
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Subjects requiring urgent surgical intervention for advanced Acanthamoeba keratitis in either eye (e.g., for advanced corneal thinning/melting etc.).
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Subject with known or suspected allergy to biguanides, diamidines or intolerance to any other ingredient of the investigational treatments.
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Subject affected by immunodeficiency diseases or taking systemic immunosuppressive therapy.
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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.
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If female, pregnancy, planned pregnancy, or breast-feeding
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | San Raffaele Hospital | Milano | Italy | ||
2 | SS Giovanni E Paolo Hospital | Venice | Italy | ||
3 | University Clinical Center Medical University of Silesia | Katowice | Poland | ||
4 | Moorfields Hospital | London | United Kingdom | ||
5 | Manchester Royal Eye Hospital | Manchester | United Kingdom | ||
6 | University Hospital Southampton | Southampton | United Kingdom |
Sponsors and Collaborators
- SIFI SpA
Investigators
- Principal Investigator: John Dart, MD, Moorfield's Hospital London
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 043SI