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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03274895
Other study ID # 043/SI
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
See also
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