Safety and Pharmacokinetic Study of Intranasal 2-DG in Healthy Volunteers

Overview

2-DG-01 is a randomized, double-blind, placebo-controlled, single and multiple ascending dose phase 1 study assessing safety, tolerability and pharmacokinetics of 2-DG in normal healthy volunteers (NHV). The safety and pharmacokinetics of 2-DG are assessed after single or multiple intranasal administrations.

Full Title of Study: “A Single/Multiple Ascending Dose Phase 1 Study Of The Safety, Tolerability, And Pharmacokinetics Of Intranasal 2-Deoxy-D-Glucose In Normal Healthy Volunteers”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Prevention
  • Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Study Primary Completion Date: June 2023

Detailed Description

2-DG-01 is a randomized, placebo-controlled, double- blind single and multiple ascending dose phase 1 study in normal healthy male and female volunteers aged 18 years or older. The primary objective of this study is to assess the clinical safety and tolerability of intranasal 2-DG in NHVs. The secondary objective of this study is to assess the human pharmacokinetics of 2-DG. The study is divided in two sub-parts: Part A, a single ascending dose (SAD) study of 2-DG and Part B, a multiple ascending dose (MAD) study. Part A consists of 3 cohorts: Cohorts 1 and 2 with a randomization ratio for 2-DG to placebo of 4:1 and Cohort 3 with a randomization ratio for 2-DG to placebo of 8:2. Part B consists of 3 cohorts: Cohort 4 with a a randomization ratio for 2-DG to placebo of 4:1 and Cohorts 5 and 6 with a randomization ratio for 2-DG to placebo of 8:2. Cohorts 1, 2 and 4 will also be controlled by randomized intranasal application of placebo into the opposite nostril to obtain an intra-individual estimate for local tolerability. Other cohorts will receive either 2-DG or placebo into both nostrils. Interim safety reviews are performed by a Data Monitoring Committee.

Interventions

• Drug: 2-Deoxyglucose
  • Intranasal administration
• Other: Placebo
  • Intranasal administration

Arms, Groups and Cohorts

• Active Comparator: Study drug
  • Each subject receives either a single dose (SAD) or a multiple dose (MAD) of a 3.5% 2-Deoxyglucose as nasal spray solution. The starting dose for the first cohort is 3.5 mg/day up to a maximum of 84 mg/day at cohort 6.
• Placebo Comparator: Placebo
  • Each subject receives either a single (SAD) or multiple (MAD) dose of placebo. The dose for each cohort is corresponding the amount of solution needed in the verum group.

Clinical Trial Outcome Measures

Primary Measures

• Adverse drug reactions (ADRs)
  • Time Frame: until 24 hours after single drug dosing
  • Number of ADRs after a single dose of 2-DG assessed by type, frequency and severity of ADRs graded as per Common Terminology Criteria for Adverse Events (CTCAE).
• Adverse drug reactions (ADRs)
  • Time Frame: until 168 hours after start of multiple drug dosing
  • Number of ADRs after multiple doses of 2-DG assessed by type, frequency and severity of ADRs graded as per Common Terminology Criteria for Adverse Events (CTCAE).

Secondary Measures

• Biodistribution of a single dose of 2-DG
  • Time Frame: baseline,0.5 hours, 2 hours, 4 hours, 6 hours after single drug dosing
  • Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).
• Biodistribution of multiple doses of 2-DG
  • Time Frame: baseline, 12 hours, 15 hours, 24 hours, 72 hours, 168 hours after start of multiple drug dosing
  • Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).
• Local tolerability of a single dose of 2-DG
  • Time Frame: baseline, 6 hours, 24 hours after single drug dosing
  • Abnormal physical examination findings in the nasal cavity (type, frequency, severity of medical abnormalities, scoring of self-reported symptoms).
• Local tolerability of multiple doses of 2-DG
  • Time Frame: baseline, 3 hours, 12 hours, 24 hours after start of multiple drug dosing
  • Abnormal physical examination findings in the nasal cavity (type, frequency, severity of medical abnormalities, scoring of self-reported symptoms).
• Olfactory function after a single dose of 2-DG
  • Time Frame: baseline, 24 hours after single drug dosing
  • Change in olfactory capacity using sniffing sticks measured by Threshold-Discrimination-Identification score (TDI score). Minimum value = 0 , maximum value= 48. A higher score means a better outcome.
• Olfactory function after multiple doses of 2-DG
  • Time Frame: baseline, 24 hours, 72 hours, 168 hours after start of multiple drug dosing
  • Change in olfactory capacity using sniffing sticks measured by Threshold-Discrimination-Identification score (TDI score). Minimum value = 0 , maximum value= 48. A higher score means a better outcome.
• Premature terminations due to ADRs after a single dose of 2-DG
  • Time Frame: until 24 hours after single drug dosing
  • Number of premature terminations due to ADRs that are assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
• Premature terminations due to ADRs after multiple doses of 2-DG
  • Time Frame: until 168 hours after start of multiple drug dosing
  • Number of premature terminations due to ADRs that are assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
• Adverse events after single dose 2-DG
  • Time Frame: until 24 hours after single drug dosing
  • Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
• Adverse events after multiple doses 2-DG
  • Time Frame: until 168 hours after start of multiple drug dosing
  • Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).

Participating in This Clinical Trial

Inclusion Criteria

• Healthy male or female volunteers, age ≥ 18 years old at screening – Females must be post-menopausal (> 1 year since last menstruation) – Able to comprehend and to give informed consent – Able to cooperate with the investigator, to comply with the requirements of the study, and to complete the full sequence of protocol-related procedures – Undergone full immunisation against SARS-CoV2 or status post infection with SARS-CoV2 (both as defined by the Austrian Ministry of Health) Exclusion Criteria:

• Frequent epistaxis (equal to or greater than 1/month) – Hypo- or anosmia – Symptoms of rhinitis, allergy or common cold disease at screening and at study initiation – Medical history of diabetes mellitus of any type – Clinically relevant abnormal findings at screening – Preceding nasal surgery or sinus surgery – Medical history of allergic rhinitis or chronic condition of the upper or lower respiratory tract with active symptoms within 30 days prior to screening – SARS-CoV-2 infection positive by PCR test at screening – Vulnerable subjects as defined by GCP – Subjects in a dependency relationship towards the investigators, e.g. as employees – Substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the investigator for the subject to be able to comply fully with study procedures – Use of medication (including prophylactic treatments) during 2 weeks before the start of the study, which in the judgment of the investigator may adversely affect the subject's welfare or the integrity of the study's results – Concurrent treatment with other experimental product or participation in another clinical trial with any investigational product within 30 days or 5 elimination half-lives (whichever is longer) prior to treatment start – Scheduled vaccination appointments during the study period

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 99 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • G.ST Antivirals GmbH
• Provider of Information About this Clinical Study
  • Sponsor