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

NCT ID: NCT04576312

Last Updated: 2021-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-29
• Study Completion Date: 2020-12-04

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

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: EXPERIMENTAL

UNI911 inhalation 1% and intranasal spray 1%

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Cohort 2

Single dose of UNI911 inhalation (1 mL 1% \~ 8,4 mg) and intranasal spray (2 x 150 µL, 1% \~ 2,5 mg)

Group Type: EXPERIMENTAL

UNI911 inhalation 1% and intranasal spray 1%

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Cohort 3

Single dose of UNI911 inhalation (3 mL 1% \~ 25,2 mg) and intranasal spray (2 x 150 µL, 1% \~ 2,5 mg)

Group Type: EXPERIMENTAL

UNI911 inhalation 1% and intranasal spray 1%

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Cohort 4

Single dose of UNI911 inhalation (6 mL 1% \~ 50,4 mg) and intranasal spray (2 x 150 µL, 1% \~ 2,5 mg)

Group Type: EXPERIMENTAL

UNI911 inhalation 1% and intranasal spray 1%

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

UNI911 inhalation 1% and intranasal spray 1%

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

UNI911 inhalation 1% and intranasal spray 1%

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

UNI911 inhalation 1% and intranasal spray 1%

Intervention Type: DRUG

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 (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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

UNION therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jesper Sonne, MD, DMSci

Role: PRINCIPAL_INVESTIGATOR

Dantrials Aps

Locations

DanTrials ApS

Copenhagen, , Denmark

Countries

Denmark

Other Identifiers

2020-002049-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UNI911-101

Identifier Type: -

Identifier Source: org_study_id