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

Sponsor

G.ST Antivirals GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05314933

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

6.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Nasopharyngitis	Drug: 2-Deoxyglucose Other: Placebo	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Mar 3, 2022

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Adverse drug reactions (ADRs) [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) [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 Outcome Measures

Biodistribution of a single dose of 2-DG [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 [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 [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 [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 [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 [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 [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 [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 [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 [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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
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