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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Acute Nasopharyngitis

Intervention / Treatment
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* Drug: 2-Deoxyglucose
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study drug<br>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<br>* Intranasal administration<br>* Other names: 2-Deoxy-D-glucose;|
| Placebo Comparator: Placebo<br>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<br>* Intranasal administration<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Virus disease, Respiratory infection, Common cold virus, Rhinovirus