Safety of Ascending Doses of Niclosamide (UNI911 INHALATION) in Healthy Volunteers

Phase 1 Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Assess the Safety of Ascending Doses of UNI911 INHALATION in Healthy Volunteers in Preparation for Evaluation in Adults With COVID-19

This is a Phase 1 Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Assess the Safety of Ascending Doses of UNI911 INHALATION in Healthy Volunteers in Preparation for Evaluation in Adults with COVID-19

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: UNI911 inhalation 1% and intranasal spray 1%; Drug: Placebo

Detailed Description

This is a Phase 1 Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Assess the Safety of Ascending Doses of UNI911 INHALATION in Healthy Volunteers in Preparation for Evaluation in Adults with COVID-19

64 subjects will be sequentially enrolled to receive dosage of UNI911 INHALATION or placebo. 4 sentinel subjects (one per cohort 1, 2 ,3 and 4 ) will be treated in an open-label manner to confirm the safety of each dose sequentially. 40 subjects will be randomly assigned (3:1) to either active or placebo. For the last 2 cohorts, a total of 20 healthy volunteers will be enrolled to receive multiple doses of UNI911 INHALATION.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • DanTrials ApS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria (main ones):

1. Signed Informed Consent Form (ICF)
2. Male or non-pregnant and non-lactating female who is abstinent or agrees to use effective contraceptive methods throughout the course of the study. Females must have a negative urine beta-human chorionic gonadotropin hormone (hCG) pregnancy test prior to dosing. (Women who are postmenopausal or who had tubal ligation/hysterectomy do not need to have a pregnancy test done and do not need to agree to use contraception.)
3. ECG without clinically significant abnormalities (including QTcF < 450 ms)
4. Age ≥ 18 and < 65 years at the time of signing ICF
5. Normally active and in good health by medical history and physical examination
6. Minimum 80% of predicted lung function, including FEV1 after beta2-agonist, TLC, DCO, and CPET with pulse oximetry
7. Chest X-ray without clinically significant abnormalities

Exclusion Criteria (main ones):

1. Enrollment in an UNI911 study in the previous 6 months
2. Clinically significant allergy (as judged by the investigator) or history of significant adverse reaction to niclosamide or related compounds, to any of the excipients used.
3. Underlying condition that may interfere with inhalation of the IP
4. Current acute or chronic condition (incl. COPD, asthma, or other severe respiratory disease, CV disease, diabetes mellitus, obesity, malignant and autoimmune diseases) unless considered clinically irrelevant and stable by the investigator
5. Renal impairment (eGFR < 60 mL/min/1.73m2) or hepatic impairment (as judged by the investigator)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: QUADRUPLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; Single dose of UNI911 inhalation (4 mL 0.1% ~ 3,4 mg) and intranasal spray (2 x 150 µL, 1% ~ 2,5 mg)	Drug: UNI911 inhalation 1% and intranasal spray 1%; Niclosamide is a broad spectrum, host tageting antiviral that inhibits viral replication (by neutralizing endosomal pH) and increases viral clearance (by increasing the autophagic flux). The niclosamide 1% solution is administered as inhalation by nebulization and intranasal by a nasal spray.; Drug: Placebo; The placebo formulation contains the vehicle. The solution is administered in the same way as the active drug. Placebo was only administered for cohorts 1-5.
EXPERIMENTAL: Cohort 2; Single dose of UNI911 inhalation (1 mL 1% ~ 8,4 mg) and intranasal spray (2 x 150 µL, 1% ~ 2,5 mg)	Drug: UNI911 inhalation 1% and intranasal spray 1%; Niclosamide is a broad spectrum, host tageting antiviral that inhibits viral replication (by neutralizing endosomal pH) and increases viral clearance (by increasing the autophagic flux). The niclosamide 1% solution is administered as inhalation by nebulization and intranasal by a nasal spray.; Drug: Placebo; The placebo formulation contains the vehicle. The solution is administered in the same way as the active drug. Placebo was only administered for cohorts 1-5.
EXPERIMENTAL: Cohort 3; Single dose of UNI911 inhalation (3 mL 1% ~ 25,2 mg) and intranasal spray (2 x 150 µL, 1% ~ 2,5 mg)	Drug: UNI911 inhalation 1% and intranasal spray 1%; Niclosamide is a broad spectrum, host tageting antiviral that inhibits viral replication (by neutralizing endosomal pH) and increases viral clearance (by increasing the autophagic flux). The niclosamide 1% solution is administered as inhalation by nebulization and intranasal by a nasal spray.; Drug: Placebo; The placebo formulation contains the vehicle. The solution is administered in the same way as the active drug. Placebo was only administered for cohorts 1-5.
EXPERIMENTAL: Cohort 4; Single dose of UNI911 inhalation (6 mL 1% ~ 50,4 mg) and intranasal spray (2 x 150 µL, 1% ~ 2,5 mg)	Drug: UNI911 inhalation 1% and intranasal spray 1%; Niclosamide is a broad spectrum, host tageting antiviral that inhibits viral replication (by neutralizing endosomal pH) and increases viral clearance (by increasing the autophagic flux). The niclosamide 1% solution is administered as inhalation by nebulization and intranasal by a nasal spray.; Drug: Placebo; The placebo formulation contains the vehicle. The solution is administered in the same way as the active drug. Placebo was only administered for cohorts 1-5.
EXPERIMENTAL: Cohort 5; UNI911 inhalation (6 mL 1% ~ 50,4 mg) and intranasal spray (2 x 150 µL, 1% ~ 2,5 mg) BID for 2,5 days.	Drug: UNI911 inhalation 1% and intranasal spray 1%; Niclosamide is a broad spectrum, host tageting antiviral that inhibits viral replication (by neutralizing endosomal pH) and increases viral clearance (by increasing the autophagic flux). The niclosamide 1% solution is administered as inhalation by nebulization and intranasal by a nasal spray.; Drug: Placebo; The placebo formulation contains the vehicle. The solution is administered in the same way as the active drug. Placebo was only administered for cohorts 1-5.
EXPERIMENTAL: Cohort 6; UNI911 inhalation (1 mL 1% ~ 8,4 mg) and intranasal spray (2 x 150 µL, 1% ~ 2,5 mg) BID for 6,5 days.	Drug: UNI911 inhalation 1% and intranasal spray 1%; Niclosamide is a broad spectrum, host tageting antiviral that inhibits viral replication (by neutralizing endosomal pH) and increases viral clearance (by increasing the autophagic flux). The niclosamide 1% solution is administered as inhalation by nebulization and intranasal by a nasal spray.
EXPERIMENTAL: Cohort 7; UNI911 inhalation (3 mL 1% ~ 25,2 mg) and intranasal spray (2 x 150 µL, 1% ~ 2,5 mg) BID for 6,5 days.	Drug: UNI911 inhalation 1% and intranasal spray 1%; Niclosamide is a broad spectrum, host tageting antiviral that inhibits viral replication (by neutralizing endosomal pH) and increases viral clearance (by increasing the autophagic flux). The niclosamide 1% solution is administered as inhalation by nebulization and intranasal by a nasal spray.
PLACEBO_COMPARATOR: Placebo (applicable for cohorts 1-5); Placebo, administered in a double-blinded fashion (except for the first subjects of cohorts 1-4) at the same dose and frequency as UNI911 inhalation and intranasal spray.	Drug: Placebo; The placebo formulation contains the vehicle. The solution is administered in the same way as the active drug. Placebo was only administered for cohorts 1-5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess safety of UNI911 INHALATION in healthy volunteers: AE frequency	AE frequency in each cohort and treatment group	Up to Day 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameters: Cmax	Maximum concentration of active drug molecules in blood (Cmax)	Up to Day 4 of participant treatment
Pharmacokinetic Parameters: Tmax	Time to reach maximum level (Tmax)	Up to Day 4 of participant treatment
Pharmacokinetic Parameters: AUC	Area Under the Curve of drug level in blood versus time (AUC)	Up to Day 4 of participant treatment
Pharmacokinetic Parameters: Half life	Half life	Up to Day 4 of participant treatment

Collaborators and Investigators

• Sponsor: UNION therapeutics
• Investigators: Principal Investigator: Jesper Sonne, MD, DMSci, DanTrials ApS

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 29, 2020
• Primary Completion (ACTUAL): December 4, 2020
• Study Completion (ACTUAL): December 4, 2020

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (ACTUAL): October 6, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 26, 2021
• Last Update Submitted That Met QC Criteria: August 20, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: UNI911-101; 2020-002049-40 (EUDRACT_NUMBER)

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