Study to Evaluate Safety, Tolerability & PK of rhNGF in Healthy Volunteers

NCT03836859 | Completed Phase 1 Results FDA Drug

• 1 other identifier: NGF0117
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the safety and tolerability of a single short-term and a multiple dose scheme of rhNGF when administered as eye drops in healthy subjects of Japanese ethnicity. The secondary objective of this study is to assess the pharmacokinetics of single and multiple doses of rhNGF when administered as eye drops in healthy subjects of Japanese ethnicity.

Conditions

Healthy Volunteers

Keywords

Tolerability and PK

Outcome Measures

Primary Outcomes (5)

• Number of Treatment Emergent Adverse Events (TEAEs).

  TEAEs were defined as an adverse event (AE), which started after the first dose of study treatment. These comprise AEs during the treatment and follow-up period. For TEAE the number of events was provided.

  On Day 1 (single dose scheme), Days 2-6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3), and Day 35-42 (FU 4)

• Number of Treatment Emergent Adverse Events During First Dose Schedule (TEAEs Dose 1).

  TEAEs Dose 1 were defined as TEAEs, which started after the first dose of study treatment and before administration of the first dose at Treatment Day 2. For TEAE the number of events was provided.

  During first dose schedule (TEAE Dose 1, which started after first dose of study treatment at Day 1 till before administration of the first dose at Treatment Day 2)

• Number of Treatment Emergent Adverse Events During Second Dose Schedule (TEAEs Dose 2).

  TEAEs Dose 2 were defined as TEAEs, which started on/after the first dose at Treatment Day 2 and before Follow-Up Day 7 visit.

  During second dose schedule (TEAE Dose 2, which started on/after the first dose at Treatment Day 2 till before Follow-Up Day 7 (FU1) visit

• Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Single Dose

  Change from baseline in VAS ocular tolerability score in study eye at Treatment Day 2 predose (Tolerability of 1x0.70 μg rhNGF per day) for overall is presented. In this context, "Baseline" was defined as the pre-treatment assessment at the Baseline (D-1) visit. A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale.

  at Treatment Day 2 pre-dose

• Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Multiple Dose

  Change from baseline in VAS ocular tolerability score in study eye at Day 2 8h, Day 3 predose, Day 6 pre-dose, Day 6 8h, Day 7 (FU1), Day 8 (FU2), Day 16 (FU3) (Tolerability of 6x0.70 μg rhNGF per day) for overall is presented. In this context, "Baseline" was defined as the pre-treatment assessment at the Baseline (D-1) visit.A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale.

  at Day 2 8h, Day 3 predose, Day 6 pre-dose, Day 6 8h, Day 7 (FU1), Day 8 (FU2), Day 16 (FU3)

Secondary Outcomes (11)

• Number of Follow-Up AEs (FUAE)

  on or after Follow-Up Day 7 (FU1)

• Number of Ocular TEAEs by Eyes

  On Day 1 (single dose scheme), Days 2-6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3), and Day 35-42 (FU 4)

• Change From Baseline in Intraocular Pressure (IOP) by Eye Over All Visits

  on Day -1 and at Day 8 (Follow up [FU] 2) and Day 16 (FU3)

• Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits

  On Day 1 (single dose scheme), Days 2,3,6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3)

• Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.

  On Day 1 (single dose scheme), Days 2,3,6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3)

Study Arms (2)

rhNGF 20μg/mL

EXPERIMENTAL

rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.

Drug: rhNGF 20μg/mL

Placebo

PLACEBO COMPARATOR

Vehicle: formulation containing L-methionine as excipient.

Other: Placebo

Interventions

rhNGF 20μg/mL DRUG

Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF). Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF). Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.

Also known as: cenegermin

rhNGF 20μg/mL

Placebo OTHER

Vehicle: formulation containing L-methionine as excipient.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects of Japanese ethnicity, aged between 18 and 60 years inclusive, who must have all four Japanese grandparents who were born in Japan.
• Subject has to be able to communicate well with the investigator, understands and complies with the requirements of the study, and understands and signs the written volunteer informed consent form.
• Subject's systemic and ocular medical history must be considered normal in the opinion of the investigator at the Screening and Baseline visits.
• Subject with Best corrected distance visual acuity (BCDVA) score ≥83 ETDRS letters, ≤ 0.00 LogMAR \[20/20 Snellen or 1.0 decimal fraction\] in each eye at the Screening and Baseline visits.
• Normal anterior segment on external and slit lamp examination in both eyes at the Screening and Baseline visits.
• Normal posterior segment on fundus ophthalmoscopic examination in both eyes at the Screening and Baseline visits.
• Subject must be considered in good systemic health in the opinion of the investigator at the Screening and Baseline visits, as determined by:
• Subject's body mass index is between 18.5 and 30.4 kg/m2 inclusive
• A pre-study physical examination with no clinically significant abnormalities.
• Vital signs within clinically acceptable ranges for the purposes of the study (sitting systolic blood pressure \[BP\] ≥ 90 mmHg and ≤ 150 mmHg; diastolic BP ≥ 50 mmHg and ≤ 95 mmHg; heart rate ≥ 40 and ≤ 100 beats per minute; oral body temperature ≥ 35.5°C and ≤ 37.5°C).
• An ECG with no clinically significant abnormalities.
• Pre-study clinical laboratory findings within normal range or not deemed clinically significant in the opinion of the investigator if outside of the normal range
• Woman subject who meets the criteria for post-menopausal stage (post menopause is defined as the period following peri-menopause, i.e. postmenopausal after 12 months without a menstrual period and with a serum FSH value within the reference range for postmenopausal females at Screening) or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) or woman subject using oral, injected or implanted hormonal methods of contraception or with a double barrier methods of contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. A female condom and a male condom should not be used together as friction between the two can result in either product failing.
• Male subjects with female partners of child-bearing potential must use 2 different forms of highly effective contraception throughout the study and for a further 3 months after the follow-up visit and all male subjects must be willing to avoid donating sperm during this time. The following methods of contraception are considered to be highly effective: established use of oral, injected or implanted hormonal contraception; placement of an intrauterine device or intrauterine system; use of a barrier method of contraception (condom or occlusive cap with use of a spermicide); male sterilisation (post-vasectomy documentation of the absence of sperm in the ejaculate must be provided).

You may not qualify if:

• Subjects meeting any of the following criteria at Screening will be excluded from entry into the study:
• Subject has had a clinically significant illness in the 6 weeks before screening in the opinion of the investigator.
• Subject is not suitable to participate in the study in the opinion of the investigator
• Subject has participated in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
• Subject has had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or has a clinically significant allergy to drugs, foods or other materials (in the opinion of the investigator).
• amiodarone and hydroxychloroquine (210 days),
• monoclonal antibodies/ immunoglobulins/ other therapeutic proteins (120 days)
• Experimental drugs with a half life known to the Study Unit: Five half lives plus 2 weeks
• Experimental drugs with a half-life unknown to the Study Unit: 120 days
• chloroquine and flunarizine (100 days)
• fluoxetine (75 days),
• benzodiazepines different from midazolam, lorazepam and triazolam, chlorpromazine, mephenytoin, nortryptyline, phenobarbital, primidone, carbamazepine, phenytoin and phenprocoumon (35 days).
• Subject has a significant history of drug/solvent abuse or a positive drugs of abuse test at any time during the study.
• Subject has a history of alcohol abuse or currently drinks in excess of 28 units per week or has a positive alcohol breath test at any time during the study.
• Subject is a smoker or has smoked in the 6 months prior to dosing.

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead
• Cromsource: collaborator

Study Sites (1)

WCCT Global

Cypress, California, 90630, United States

Location

MeSH Terms

Interventions

cenegermin

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé farmaceutici s.p.a.

clinical.trials@dompe.com

+39 02 513831

Study Officials

• Flavio Mantelli, MD, PhD

  Dompé SpA Milan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (subject, Investigator, site staff and Sponsor's clinical research personnel)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel assignment

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: February 11, 2019
• Study Start: March 30, 2018
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: December 26, 2023
• Results First Posted: June 11, 2020

Record last verified: 2023-12

Locations

US (1)