Acanthamoeba KeratitisPhase 3NCT03274895
Polihexanide (PHMB) Eye Drops in Patients Affected by Acanthamoeba Keratitis
A Phase 3 study testing PHMB 0.08%, Propamidine 0.1% and PHMB 0.02% in people with Acanthamoeba Keratitis, run by SIFI SpA at 6 sites in 3 countries.
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) +… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Acanthamoeba Keratitis
- What is being tested?
- PHMB 0.08%, Propamidine 0.1% and PHMB 0.02%
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 13 Aug 2017to 30 Mar 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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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.
- 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.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United Kingdom3 sites
Moorfields Hospital
London
Manchester Royal Eye Hospital
Manchester
University Hospital Southampton
Southampton
About this study
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
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
Read the 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
- Conditions
- Acanthamoeba Keratitis
- Being tested
- PHMB 0.08%, Propamidine 0.1%, placebo, PHMB 0.02%
- Keywords
- polihexanide, propamidine, confocal microscopy
- Medical subject headings
- Acanthamoeba Keratitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PHMB 0.08%Drug
Also called Polihexanide 0.8 mg/ml
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%Drug
Also called Brolene eye drops
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
placeboDrug
Also called Brolene vehicle
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%Drug
Also called Polihexanide 0.2 mg/ml
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
| Study group | Role | What they receive |
|---|---|---|
| PHMB 0.08% plus placebo | Experimental | polihexanide (PHMB) 0.08% and placebo were administered in the affected eye until clinical resolution for a maximum of 12 months Receives: Drug: PHMB 0.08%; Drug: placebo |
| PHMB 0.02% plus propamidine 0.1% | Active comparator | polihexanide (PHMB) 0.02% and propamidine 0.1% were administered in the affected eye until clinical resolution for a maximum of 12 months Receives: Drug: Propamidine 0.1%; Drug: PHMB 0.02% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Resolution Rate
Percentage of patients cured 30 days after discontinuing all study therapies, within 12 months of randomization
Measured: 12 months
Secondary outcomes (2)
Time to Cure
Time needed to reach a clinical resolution
Measured: maximum 12 months
Visual Acuity
Final visual acuity (best corrected)
Measured: maximum 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2017
- Study start13 Aug 2017
- Primary completion30 Jun 2021
- Study completion30 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acanthamoeba KeratitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- SIFI SpA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Dart, MD, Principal investigator, Moorfield's Hospital London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03274895
- Sponsor's protocol ID
- 043/SI
- Status last verified
- Aug 2023
- First submitted
- 5 Sep 2017
- Last updated
- 22 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 31401556Papa 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.
PubMed 33239413Dart JKG, Papa V, Rama P, Knutsson KA, Ahmad S, Hau S, Sanchez S, Franch A, Birattari F, Leon P, Fasolo A, Kominek EM, Jadczyk-Sorek K, Carley F, Hossain P, Minassian DC. The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1. Ophthalmology. 2024 Mar;131(3):277-287. doi: 10.1016/j.ophtha.2023.09.031. Epub 2023 Oct 5.
PubMed 37802392
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03274895
- Acronym / sponsor ID
- 043/SI
- Conditions
- Acanthamoeba Keratitis
- Keywords
- polihexanide, propamidine, confocal microscopy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- SIFI SpAIndustry (pharma, biotech, devices)
- Study start
- 13 Aug 2017 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Mar 2022 (actual)
- First posted
- 7 Sep 2017 (actual)
- Results
- Posted 2 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PHMB 0.08% plus placebo | Experimental | Drug: PHMB 0.08%, Drug: placebopolihexanide (PHMB) 0.08% and placebo were administered in the affected eye until clinical resolution for a maximum of 12 months |
| PHMB 0.02% plus propamidine 0.1% | Active comparator | Drug: Propamidine 0.1%, Drug: PHMB 0.02%polihexanide (PHMB) 0.02% and propamidine 0.1% were administered in the affected eye until clinical resolution for a maximum of 12 months |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PHMB 0.08%Also: Polihexanide 0.8 mg/ml16 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 | Drug | PHMB 0.08% plus placebo |
| Propamidine 0.1%Also: Brolene eye drops16 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 | Drug | PHMB 0.02% plus propamidine 0.1% |
| placeboAlso: Brolene vehicle16 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 | Drug | PHMB 0.08% plus placebo |
| PHMB 0.02%Also: Polihexanide 0.2 mg/ml16 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 | Drug | PHMB 0.02% plus propamidine 0.1% |
Primary outcome
Clinical Resolution Rate
Time frame: 12 months
Percentage of patients cured 30 days after discontinuing all study therapies, within 12 months of randomization
2 secondary outcomes
Time to Cure
Time frame: maximum 12 months
Visual Acuity
Time frame: maximum 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31401556Papa 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.
- Background: PubMed 33239413Papa 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.
- Derived from this study: PubMed 37802392Dart JKG, Papa V, Rama P, Knutsson KA, Ahmad S, Hau S, Sanchez S, Franch A, Birattari F, Leon P, Fasolo A, Kominek EM, Jadczyk-Sorek K, Carley F, Hossain P, Minassian DC. The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1. Ophthalmology. 2024 Mar;131(3):277-287. doi: 10.1016/j.ophtha.2023.09.031. Epub 2023 Oct 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Dart, MD principal investigator
Moorfield's Hospital London
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PHMB 0.08%, Propamidine 0.1% and PHMB 0.02% in people with Acanthamoeba Keratitis, run by SIFI SpA at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom, Italy, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Resolution Rate (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03274895, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.