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

• ClinicalTrials.gov Identifier: NCT03274895
• Recruitment Status: Active, not recruiting
• First Posted: September 7, 2017
• Last Update Posted: October 23, 2020
• Sponsor: SIFI SpA
• Information provided by (Responsible Party): SIFI SpA

Tracking Information

• First Submitted Date: September 5, 2017
• First Posted Date: September 7, 2017
• Last Update Posted Date: October 23, 2020
• Actual Study Start Date: August 13, 2017
• Estimated Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 5, 2017)

Clinical resolution rate [ Time Frame: 12 months ]

Percentage of patients cured 30 days after discontinuing all study therapies, within 12 months of randomization

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Polyhexamethylene Biguanide (PHMB) Ophthalmic Solution in Subjects Affected by Acanthamoeba Keratitis
• 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

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

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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acanthamoeba Keratitis

Intervention

• 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 Name: 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 Name: 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 Name: 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 Name: Polyhexamethylene Biguanide 0.02%

Study Arms

• 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
  Interventions:

  • Drug: PHMB 0.08%
  • Drug: placebo
• 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
  Interventions:

  • Drug: Propamidine 0.1%
  • Drug: PHMB 0.02%

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 5, 2017): 130
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2021
• Estimated Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 13 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, Poland, United Kingdom

Administrative Information

• NCT Number: NCT03274895
• Other Study ID Numbers: 043SI
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: SIFI SpA
• Study Sponsor: SIFI SpA
• Collaborators: Not Provided

Investigators

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

• PRS Account: SIFI SpA
• Verification Date: October 2020