Study of the Safety of USB005 in Healthy Volunteers

NCT03615196 | Completed Phase 1 FDA Drug

• 1 other identifier: USB005-2017-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety, tolerability and pharmacokinetics of USB005 (aclerastide) Ophthalmic Solution.

Conditions

Healthy Volunteers

Keywords

NorLeu3-A(1-7); USB005; aclerastide; corneal repair; corneal injury

Outcome Measures

Primary Outcomes (4)

• Percentage of volunteers with dose limiting toxicities in each cohort

  36 days

• Percentage of volunteers in each cohort with ocular adverse events

  36 days

• Percentage of volunteers in each cohort with systemic adverse events

  36 days

• Percentage of volunteers with clinically significant out of range laboratory values

  36 days

Secondary Outcomes (6)

• Maximum observed concentrations (Cmax)

  36 days

• Time to reach maximum observed plasma concentration (Tmax) after multiple ascending dose

  36 days

• Apparent terminal half-life (T1/2) after multiple ascending dose

  36 days

• Area under the plasma concentration versus time curve from time 0 to infinity (AUCinf)

  36 days

• Area under the plasma concentration versus time curve up to the last measurable concentration (AUC0-last)

  36 days

Study Arms (5)

USB005 0.03%

EXPERIMENTAL

USB005 (aclerastide) Ophthalmic Solution 0.03%; single eye drop instillation three times a day to one eye during a 28-day treatment period (84 treatments)

Drug: USB005 (aclerastide) Ophthalmic Solution

USB005 0.1%

EXPERIMENTAL

USB005 (aclerastide) Ophthalmic Solution 0.1%; single eye drop instillation three times a day to one eye during a 28-day treatment period (84 treatments)

Drug: USB005 (aclerastide) Ophthalmic Solution

USB005 0.3%

EXPERIMENTAL

USB005 (aclerastide) Ophthalmic Solution 0.3%; single eye drop instillation three times a day to one eye during a 28-day treatment period (84 treatments)

Drug: USB005 (aclerastide) Ophthalmic Solution

USB005 0.45%

EXPERIMENTAL

USB005 (aclerastide) Ophthalmic Solution 0.45%; single eye drop instillation three times a day to one eye during a 28-day treatment period (84 treatments)

Drug: USB005 (aclerastide) Ophthalmic Solution

USB005 Placebo

PLACEBO COMPARATOR

USB005 Ophthalmic Solution Placebo; single eye drop instillation three times a day to one eye during a 28-day treatment period (84 treatments)

Drug: USB005 Ophthalmic Solution Placebo

Interventions

USB005 (aclerastide) Ophthalmic Solution DRUG

Aclerastide (\[Nle3\]-Angiotensin II (1-7)) is aseptically formulated in USB005 Ophthalmic Solution for topical ophthalmic administration. Active pharmaceutical ingredient (API) levels ranging from 0.03% to 0.45% are formulated in a sterile vehicle consisting of 0.06% Sodium Phosphate Monobasic Anhydrous, USP; 3% Glycerol, USP; 1.4% Polyvinyl Alcohol, USP; and 0.5% Hydroxyethylcellulose (HEC 250 HHX), NF in Sterile Water for Injection, USP.

USB005 0.03%; USB005 0.1%; USB005 0.3%; USB005 0.45%

USB005 Ophthalmic Solution Placebo DRUG

A clinical placebo formulated with the same excipients and packaged in the same container closure system as the active product, USB005 (aclerastide) Ophthalmic Solution.

USB005 Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female volunteers, aged 18-64 years (inclusive) at the time of signing the ICF;
• For females:
• Surgically sterilized (eg, hysterectomy or bilateral oophorectomy) for at least 6 months prior to screening or postmenopausal (postmenopausal women must have no menstrual bleeding for at least 1 year prior to screening and menopause will be confirmed by a plasma FSH level of \>40 IU/L) or
• Women of childbearing potential must be non-lactating and agree to use a highly effective acceptable form of birth control (e.g., established hormonal birth control plus a barrier method, double barrier method: intrauterine device plus condom or spermicidal gel plus condom) from 21 days prior to dosing until 7 days after dosing, and
• Women with a negative pregnancy test (β-hCG assay) at screening and Day -1;
• Weight of 45-100 kg and BMI of 17.5-35 kg/m2 (inclusive);
• Blood pressure no greater than 120/80 mm Hg (inclusive);
• Healthy, as determined by medical history, physical examination, vital signs, and clinical laboratory tests, unless the Investigator considers an abnormality to be clinically irrelevant;
• IOP measurement oculus uterque (OU, both eyes) \<21 mm Hg at screening and Day -1;
• BCVA 20/30 or better (LogMAR and Snellen Equivalent) at both the screening visit and Day -1 in at least 1 eye;
• Normal vision as determined by comprehensive ocular examination;
• Able and willing to provide signed, written, informed consent;
• Willing to communicate with the Investigator and site staff and comply with all study procedures and requirements;
• Willing and able to be confined to the clinical study site as required by the protocol.

You may not qualify if:

• Any history of severe ocular trauma in either eye at any time;
• Any history of previous intraocular or ocular laser surgery within the past 3 months or any refractive surgery procedure within the past 6 months of the screening visit in either eye;
• Any condition preventing reliable ocular assessment (eg, applanation tonometry, fundus examination) in either eye;
• Intended use of contact lenses during this study or 1 week before Day -1;
• Current or chronic history of ocular disease within the past 3 months of screening visit in either eye;
• Current or chronic history of ocular infection (bacterial, viral or fungal) or corneal irritation within the past 3 months of screening visit in either eye OR ongoing or recurrent ocular inflammation (ie, moderate to severe blepharitis, allergic conjunctivitis, peripheral ulcerative keratitis, scleritis, uveitis) in either eye;
• Abnormal tearing, OR expected regular use of prescription or expected use of OTC tear substitutes within 4 weeks prior to Day -1, and for the duration of the study;
• Previous or expected use of ocular (topical, periocular, intravitreal), local (inhaled or nasal), or systemic steroid or glucocorticoid medications within 4 weeks prior to Day -1, and for the duration of the study;
• At the ophthalmic investigator's discretion, any volunteers who have a history of any significant ocular conditions in either eye that would contraindicate the use of the study medication, or that might affect the study conduct, or the interpretation of the study results;
• Use of any non-diagnostic topical ophthalmic solutions through the duration of the study;
• Clinically significant metabolic disease such as diabetes, asthma, or hypertension (ie, blood pressure \>120/80 mm Hg on two successive visits during screening);
• Taken any nicotine-containing products in the last 6 months prior to dosing or for the duration of the study;
• At the Investigator's discretion, any volunteers with a history or presence of clinically significant cardiovascular disorders, including a history of orthostatic hypotension, arrhythmia and syncope (including vasovagal syncope), or respiratory, metabolic, renal, hepatic, immunologic, endocrine, dermatologic, venereal, hematologic, neurologic, psychiatric (eg, major depression with suicidal ideation, or suicide attempt), malignant neoplasm, musculoskeletal, connective tissue, urinary disease or disorders;
• History of clinically significant drug or food allergy;
• Positive HIV, hepatitis B or C viral test at screening;

Sponsors & Collaborators

• US Biotest, Inc.: lead
• United States Department of Defense: collaborator

Study Sites (1)

WCCT Global, Inc.

Cypress, California, 90630, United States

Location

Related Publications (1)

• Abdallah WF, Louie SG, Zhang Y, Rodgers KE, Sivok E, S diZerega G, Humayun MS. NorLeu3A(1-7) Accelerates Clear Corneal Full Thickness Wound Healing. Invest Ophthalmol Vis Sci. 2016 Apr 1;57(4):2187-94. doi: 10.1167/iovs.15-18515.

  PMID: 27116546 BACKGROUND

MeSH Terms

Conditions

Corneal Injuries

Interventions

aclerastide; Ophthalmic Solutions

Condition Hierarchy (Ancestors)

Eye Injuries; Facial Injuries; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Corneal Diseases; Eye Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• Michael Sheety, MD

  WCCT Global, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 3, 2018
• Study Start: July 25, 2018
• Primary Completion: November 8, 2018
• Study Completion: April 2, 2019
• Last Updated: April 4, 2019

Record last verified: 2019-04

Locations

US (1)