First-in-Human Study of LHA510 in Elderly Subjects and Patients With Age-Related Macular Degeneration
Condition: Age-Related Macular Degeneration
MeSH terms: Macular Degeneration
Intervention: LHA510 Ophthalmic Suspension; LHA510 Vehicle
Intervention description: Ophthalmic suspension in 4 concentration levels topically administered in Part 1 and Part 2; Inactive ingredients used for masking purposes
Intervention MeSH terms: Acrizanib
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 110.0
Sex: All
Minimum age: 55 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: LHA510; First in human; Safety; Tolerability; Pharmacokinetics; Elderly; Age-Related Macular Degeneration; AMD; Ocular; Eye drop

Summary:

      The purpose of this first-in-human study is to assess the local ocular and systemic safety
      and tolerability of LHA510 eye drops when administered at various concentrations and dosing
      frequencies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provide written informed consent.

          -  Vital signs within the following ranges:

               -  oral body temperature between 35.0-37.5 °C

               -  systolic blood pressure, 90-150 mm Hg

               -  diastolic blood pressure, 50-90 mm Hg

               -  pulse rate, 40 - 100 bpm.

          -  Weigh at least 50 kg.

          -  Able to communicate well with the investigator.

          -  Able to understand and comply with the requirements of the study.

        Additional eligibility criteria for Part 2 (AMD subjects):

          -  Evidence of AMD in one or both eyes.

          -  Age 55-90.

          -  Other protocol-defined inclusion criteria may apply.

        Exclusion Criteria:

          -  Any currently active ocular condition that requires use of topical eye drops.

          -  Use of contact lens over the course of the study.

          -  Abnormal corneal examination results at screening or eligibility.

          -  History of any ocular surgery within the past 6 months prior to study participation.

          -  Use of other investigational drugs within 30 days of enrollment.

          -  History of hypersensitivity or allergy to any of the study drugs (including
             fluorescein) or to drugs of similar chemical classes.

          -  History of clinically significant ECG abnormalities, or any ECG abnormality at
             screening or eligibility.

          -  Known history or current clinically significant arrhythmias.

          -  History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years.

          -  Pregnant or nursing (lactating) women.

          -  Women of child-bearing potential.

          -  Use of any prohibited medication as specified in the protocol.

          -  Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial
             dosing.

          -  Low hemoglobin levels at screening or eligibility as specified in the protocol.

          -  Significant illness as specified in the protocol.

          -  History of drug or alcohol abuse within the 12 months prior to dosing.

        Additional exclusion criteria for Part 1 (healthy subjects):

          -  Abnormal thickness of the central retinal subfield on OCT at screening.

          -  History of any chronic eye disease other than refractive error, incipient cataract,
             strabismic amblyopia, or anisometropic amblyopia.

        Additional exclusion criteria for Part 2 (AMD subjects):

          -  Any of the following treatments to the study eye within 28 days prior to dosing:
             ranibizumab (Lucentis®), aflibercept (Eylea®), bevacizumab (Avastin®), pegaptanib
             (Macugen®), or any other VEGF inhibitor.

          -  Patients who have required and received regular monthly injections of these drugs in
             the months preceding the study.