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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Nasopharyngitis
• Intervention / Treatment: Drug: 2-Deoxyglucose; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: 2-Deoxyglucose; Intranasal administration; Other Names: 2-DG; 2-Deoxy-D-glucose
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.	Other: Placebo; Intranasal administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse drug reactions (ADRs)	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).	until 24 hours after single drug dosing
Adverse drug reactions (ADRs)	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).	until 168 hours after start of multiple drug dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biodistribution of a single dose of 2-DG	Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).	baseline,0.5 hours, 2 hours, 4 hours, 6 hours after single drug dosing
Biodistribution of multiple doses of 2-DG	Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).	baseline, 12 hours, 15 hours, 24 hours, 72 hours, 168 hours after start of multiple drug dosing
Local tolerability of a single dose of 2-DG	Abnormal physical examination findings in the nasal cavity (type, frequency, severity of medical abnormalities, scoring of self-reported symptoms).	baseline, 6 hours, 24 hours after single drug dosing
Local tolerability of multiple doses of 2-DG	Abnormal physical examination findings in the nasal cavity (type, frequency, severity of medical abnormalities, scoring of self-reported symptoms).	baseline, 3 hours, 12 hours, 24 hours after start of multiple drug dosing
Olfactory function after a single dose of 2-DG	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.	baseline, 24 hours after single drug dosing
Olfactory function after multiple doses of 2-DG	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.	baseline, 24 hours, 72 hours, 168 hours after start of multiple drug dosing
Premature terminations due to ADRs after a single dose of 2-DG	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).	until 24 hours after single drug dosing
Premature terminations due to ADRs after multiple doses of 2-DG	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).	until 168 hours after start of multiple drug dosing
Adverse events after single dose 2-DG	Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).	until 24 hours after single drug dosing
Adverse events after multiple doses 2-DG	Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).	until 168 hours after start of multiple drug dosing

Collaborators and Investigators

• Sponsor: G.ST Antivirals GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Actual): August 1, 2023
• Study Completion (Actual): September 27, 2023

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: March 29, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Respiratory infection; Rhinovirus; Virus disease; Common cold virus
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Picornaviridae Infections; Pharyngitis; Common Cold; Nasopharyngitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Deoxyglucose
• Other Study ID Numbers: 2-DG-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No