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Open Label, Sequential-dose Study of PA5108 Latanoprost FA SR Ocular Implant for Mild-moderate Glaucoma

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ClinicalTrials.gov Identifier: NCT04060758
Recruitment Status : Not yet recruiting
First Posted : August 19, 2019
Last Update Posted : November 6, 2019
Sponsor:
Information provided by (Responsible Party):
PolyActiva Pty Ltd

Tracking Information
First Submitted Date  ICMJE August 5, 2019
First Posted Date  ICMJE August 19, 2019
Last Update Posted Date November 6, 2019
Estimated Study Start Date  ICMJE November 2019
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2019)
  • Effective dose [ Time Frame: Intraocular Pressure (IOP) change measured at; baseline, week 12 and week 26. ]
    Determine the minimum effective dose (as daily release rate of LtpFA) that achieves an IOP lowering effect >20% with minimal adverse events.
  • Safety and Tolerability-incidence of treatment emergent Adverse Events [ Time Frame: Incidence of Treatment-Emergent Adverse Events throughout the study (up to 1 year). ]
    Assess the safety and tolerability of PA5108 Latanoprost FA SR Ocular Implant in adults with Open Angle Glaucoma (Primary or Secondary) or Ocular Hypertension. Incidence of Treatment-Emergent Adverse Events from visit 1 until end of study. Safety laboratory evaluations (biochemistry, haematology, urinalysis). Physical examinations and vital signs. Changes in ocular examinations from baseline to end of study.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04060758 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2019)
Ease of Use [ Time Frame: At visit 2-Day 0, after use of device to insert the implant into the eye. ]
Assess the ease of use of the bespoke administration device- Administering ophthalmologist's assessment of ease of use of the bespoke administration device, verbal communication.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open Label, Sequential-dose Study of PA5108 Latanoprost FA SR Ocular Implant for Mild-moderate Glaucoma
Official Title  ICMJE An Open Label, Comparative, Sequential-dose, Multi-centre Study Involving Intracameral Administration of a PA5108 Latanoprost FA SR Ocular Implant Into the Eye of Patients With Mild-moderate Glaucoma
Brief Summary This is a multi-centre, open label, interventional, comparative, phase I study to identify a safe and efficacious dose (within the range of 16.2 to 60 microgram) of PA5108 (PolyActiva product code) Latanoprost free acid (FA) sustained release (SR) Ocular Implant in adults who have Open Angle Glaucoma (Primary or Secondary) or Ocular Hypertension.
Detailed Description

This is a multi-centre, open label, interventional, comparative, phase Ib dose ranging study to identify a safe and efficacious dose (within the range of 16.2 to 60 microgram) of PA5108 Latanoprost FA SR Ocular Implant in adults who have Open Angle Glaucoma (Primary or Secondary) or Ocular Hypertension.

The proposed study is an adaptive dose design to determine the dose that provides the target of >20% IOP lowering effect at 12 weeks with minimal adverse events.

Up to four cohorts will be assessed from the following implant strengths:

  • 60 microgram
  • 30 microgram
  • 45 microgram
  • 16.2 microgram

A first cohort of subjects (n = 3-10) will be recruited and dosed with the 30 microgram PA5108 Latanoprost FA SR Ocular Implant. A second cohort of subjects (n = 3-10) will be recruited immediately after the first cohort and dosed with the 60 microgram PA5108 Latanoprost FA SR Ocular Implant. A third cohort of subjects (n = 3-10) will be recruited immediately after the second cohort and dosed with the 45 microgram PA5108 Latanoprost FA SR Ocular Implant.

• If the first cohort (30 microgram) achieves ≥ 30 % IOP reduction, an additional cohort of subjects (n = 3-10) will be recruited and dosed 16.2 microgram PA5108 Latanoprost FA SR Ocular Implant.

Participants will be using intraocular pressure (IOP) lowering drop therapy, including a prostaglandin analogue, as standard of care for their glaucoma. The IOP lowering eye drops will be stopped in the intent to treat eye at least 28 days and no greater than 49 days prior to the date of implant administration.

Participants will be required to have an unmedicated (post wash-out) 8:00am IOP ≥ 24 millimetre of mercury (mmHg) and ≤ 36mmHg in the intent to treat eye at either of 2 qualification visits 2-weeks apart.

Participants are also required to have an unmedicated (post wash-out) IOP ≥ 20mmHg and ≤ 36mmHg at 12noon and 16:00hrs in the same eye on the same qualification visit where the 8:00am IOP was IOP ≥ 24 mmHg and ≤ 36mmHg.

The PA5108 Latanoprost FA SR Ocular Implant will be optionally administered to one eye (unilateral) or both eyes (bilateral) of each participant. In the event of bilateral administration, each dosing will be at least 6-weeks apart.

IOP will be monitored and if it rises to ≥30% over baseline in the study eye, IOP lowering eye drops will be restarted.

The study will recruit 3-10 participants per dose level. After Screening, and IOP lowering medication wash-out eligible participants will be administered PA5108 Latanoprost FA SR Ocular Implant intracamerally to the anterior chamber of the study eye(s), by means of a custom-built injector with a 27G (Gauge) pre-loaded needle.

The study will end when all of the study implants are no longer visible in the study eye (biodegradation time point) and until IOP returns to normal clinical care range.

Participants will attend the study site for follow up on Day 1 post implant administration, and then Week 6, 12, 26 and subsequent 6-week intervals until the implant has completely biodegraded. Presence of the implant will be assessed by biomicroscopy and gonioscopy examination at Week 6 and every visit thereafter. Complete implant biodegradation will be confirmed by implant disappearance (biomicroscopy/gonioscopy) with loss of any IOP lowering effect.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Open Angle Glaucoma
Intervention  ICMJE Drug: PA5108 Latanoprost FA SR Ocular Implant
Ocular Implant
Other Name: PA5108
Study Arms  ICMJE
  • Experimental: 60 microgram
    PA5108 Latanoprost FA SR Ocular Implant which releases 60 microgram
    Intervention: Drug: PA5108 Latanoprost FA SR Ocular Implant
  • Experimental: 30 microgram
    PA5108 Latanoprost FA SR Ocular Implant which releases 30 microgram
    Intervention: Drug: PA5108 Latanoprost FA SR Ocular Implant
  • Experimental: 45 microgram
    PA5108 Latanoprost FA SR Ocular Implant which releases 45 microgram
    Intervention: Drug: PA5108 Latanoprost FA SR Ocular Implant
  • Experimental: 16.2 microgram
    PA5108 Latanoprost FA SR Ocular Implant which releases 16.2 microgram. Inclusion of this arm is dependent on result of 30 microgram arm.
    Intervention: Drug: PA5108 Latanoprost FA SR Ocular Implant
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 16, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Participants who:

  • Provide written informed consent
  • Are at least 18 years of age.
  • Diagnosis of open angle glaucoma or ocular hypertension. Diagnosis of open angle glaucoma must be classified as Grade 3 or 4 on the modified Shaffer-Etienne scale. Diagnosis of ocular hypertension must be without evidence of disc or visual field change.
  • Unmedicated (post-washout) 8:00am IOP ≥ 24 mmHg and ≤ 36mmHg in the intent to treat eye at either of two qualification visits 2 weeks apart. Additionally, the IOP at 12:00 and 16:00 hrs must be ≥ 20mmHg and ≤ 36mmHg on the same qualification visit where the 8:00am IOP was IOP ≥ 24 mmHg and ≤ 36mmHg.
  • Corrected visual acuity in each eye no less than (+0.3logMAR) or better by Early Treatment of Diabetic Retinopathy Study (EDTRS) in the study eye (equivalent to 6/12).
  • Minimum endothelial cell density of greater than or equal to 1500 cells per mm2
  • Currently managing their glaucoma with IOP lowering drop therapy, including a prostaglandin analogue.
  • Agree to comply with the contraceptive measures described in the protocol.
  • Are able and willing to follow study instructions and undergo eye examinations

Exclusion Criteria:

Participants who:

  • Have pseudoexfoliation or pigment dispersion component, history of angle closure, or narrow angles. Note: Previous laser peripheral iridotomy is NOT acceptable.
  • Have a history of or current uveitis, cystoid macular oedema (CME), or cornea oedema in the study eye.
  • Have aphakic eyes or only one eye.
  • Have significant corneal guttata in the study eye.
  • Have had any intraocular surgery, glaucoma surgery or cornea/refractive surgery in either eye within the past 6 months or anticipate a need for eye surgery (including laser) in the study eye during the study period.
  • Subjects with Fuchs' Endothelial Corneal Dystrophy (FECD) grade greater than or equal to 1 in the study eye.
  • Have a current retinal detachment or history of blunt trauma in the study eye.
  • Ocular trauma in either eye within the three months prior to screening, or ocular surgery or non-refractive laser treatment within the six months prior to screening or anticipate a need for eye surgery (including laser) in either eye during the study period.
  • Known sensitivity to any component of the product (e.g. latanoprost or polytriazole sensitivity), or to topical therapy used during course of study (e.g. povidone iodine, or anaesthetics).
  • Recent or current evidence of ocular infection or inflammation in either eye. Current evidence of clinically significant blepharitis, conjunctivitis, or a history of herpes simplex or zoster keratitis at screening in either eye.
  • Clinically significant ocular disease in either eye (e.g., corneal oedema, uveitis, severe keratoconjunctivitis sicca) which might interfere with the study, including glaucomatous damage so severe that washout of ocular hypotensive medications for 4-weeks is not judged safe (e.g., cup-disc ratio > 0.8, severe visual field defect).
  • Ocular medication in either eye of any kind within 30 days of screening, with the exception of a) ocular hypotensive medications (which must be washed out according to the provided schedule), b) lid scrubs (which may be used prior to, but not after screening) or c) lubricating drops for dry eye (which may be used throughout the study).
  • Central corneal thickness in either eye that is less than 470 µm or greater than 630 µm at screening (or a difference between the eyes >70 µm).
  • Any abnormality in either eye preventing reliable applanation tonometry, including aphakic eyes or significant corneal guttatae.
  • Clinically significant systemic disease (as determined by physician) which might interfere with the study.
  • Immunosuppressed patients.
  • Clinically significant abnormalities (as determined by the treating physician) in laboratory tests at screening.
  • Have received any investigational research agent within 30 days or five half-lives (whichever is longer) prior to the administration of the ocular implant.
  • Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.
  • Have a known or current alcohol or substance abuse problem.
  • Have progressive or relapsing haematological malignancy, a current solid tumour, or previous malignant solid tumour that is likely to recur during the period of the study (with the exception of a past history of basal or squamous cell carcinomas).
  • Have any other medical, psychiatric, or social condition which, in the opinion of the investigator, makes the participant unsuitable for participation in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Teresa Morgan 0425795597 teresa.morgan@polyactiva.com
Contact: Russell Tait +61396570700 russell.tait@polyactiva.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04060758
Other Study ID Numbers  ICMJE LATA CS102
Has Data Monitoring Committee Yes
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  ICMJE
Plan to Share IPD: No
Responsible Party PolyActiva Pty Ltd
Study Sponsor  ICMJE PolyActiva Pty Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Keith Martin Royal Victoria Eye and Ear Hospital
Principal Investigator: Michael Coote Melbourne Eye Specialists
PRS Account PolyActiva Pty Ltd
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP