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

Sponsor

UNION therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT04576312

Collaborator

(none)

Enrollment

Location

Arms

5.2

Actual Duration (Months)

12.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Covid19	Drug: UNI911 inhalation 1% and intranasal spray 1% Drug: Placebo	Phase 1

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Jun 29, 2020

Actual Primary Completion Date :

Dec 4, 2020

Actual Study Completion Date :

Dec 4, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Assess safety of UNI911 INHALATION in healthy volunteers: AE frequency [Up to Day 6]
AE frequency in each cohort and treatment group

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria (main ones):

Signed Informed Consent Form (ICF)
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.)
ECG without clinically significant abnormalities (including QTcF < 450 ms)
Age ≥ 18 and < 65 years at the time of signing ICF
Normally active and in good health by medical history and physical examination
Minimum 80% of predicted lung function, including FEV1 after beta2-agonist, TLC, DCO, and CPET with pulse oximetry
Chest X-ray without clinically significant abnormalities

Exclusion Criteria (main ones):

Enrollment in an UNI911 study in the previous 6 months
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.
Underlying condition that may interfere with inhalation of the IP
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
Renal impairment (eGFR < 60 mL/min/1.73m2) or hepatic impairment (as judged by the investigator)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DanTrials ApS	Copenhagen		Denmark

Sponsors and Collaborators

UNION therapeutics

Investigators

Principal Investigator: Jesper Sonne, MD, DMSci, Dantrials Aps

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

UNION therapeutics

ClinicalTrials.gov Identifier:

NCT04576312

Other Study ID Numbers:

UNI911-101
2020-002049-40

First Posted:

Oct 6, 2020

Last Update Posted:

Aug 26, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

COVID-19

Study Results

No Results Posted as of Aug 26, 2021