A Study to Assess the Safety, Tolerability and Pharmacokinetics of Inhaled HH-120 Aerosol in Healthy Volunteers

A Double-Blinded, Randomized, and Placebo-Controlled Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics Profile of Single and Multiple Ascending Doses of Inhaled HH-120 Aerosol in Healthy Volunteers

This is a Phase 1, randomized, double-blinded, placebo controlled, dose escalation study of HH-120 in healthy adult volunteers. HH-120 is a novel inhalable biologic being developed for COVID-19 treatment. The study aims to evaluate the safety, tolerability and pharmacokinetic profile of HH-120 administered by aerosol inhalation after single and multiple ascending doses.

Study Overview

• Status: Completed
• Conditions: COVID-19 Respiratory Infection
• Intervention / Treatment: Drug: Placebo; Biological: HH-120 Dose 1; Biological: HH-120 Dose 2; Biological: HH-120 Dose 3

Detailed Description

Approximately 48 participants will be sequentially enrolled into either 1 of 3 SAD cohorts (n=8 per cohort), or 1 of 3 MAD cohorts (n= 8 per cohort). An adaptive dose escalation schedule will be employed for both SAD and MAD parts of the study.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male or female volunteers aged 18 to 65 years (both inclusive)
2. Participants must have a body mass index between ≥ 18.0 and ≤ 32 .0 kg/m2 and a bodyweight of at least 45 kg at Screening.
3. Participants must be a non-smoker and must not have used any tobacco products within 90 days prior to Screening.
4. Participants must be in good general health, with no significant medical history, have no clinically significant abnormalities on physical examination at screening and/or before administration of the initial dose of IP.
5. Participants must have clinical laboratory values within normal range.
6. Females must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception from Screening until study completion, including the follow-up period.
7. Males must not donate sperm for at least 90 days after the last dose of IP.
8. Participants must have the ability and willingness to attend the necessary visits to the CRU.

Exclusion Criteria:

1. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
2. Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the PI's (or delegate's) opinion, could adversely affect the safety of the participant or that might interfere with the conduct of the study.
3. Presence of any underlying physical or psychological medical condition
4. Pre-existing severe obstructive disease of the respiratory system such as chronic obstructive pulmonary disease or asthma , including resolved childhood asthma, which may impact inhalation as judged by the PI, delegate, or Sponsor.
5. History or evidence o f any anatomical airway defect, which in the opinion of the PI, may impact inhalation.
6. Abnormal spirometry findings at Screening that are considered by the PI to be clinically significant, including FEV1 < 80% or FVC < 80%.
7. Blood donation of > 500 mL or significant blood loss within 60 days prior to the first IP administration or plasma donation within 7 days prior to IP administration.
8. Systemic or respiratory infection within 2 weeks before the Screening visit or fever (tympanic temperature > 37.5°C) or symptomatic viral or bacterial infection at time of Screening.
9. Current infection with SARS-CoV-2, infection within the 2 weeks prior to Screening, or a history of SARS-CoV-2 infection plus symptoms of post-COVID syndrome.
10. History of anaphylaxis or other significant allergy in the opinion of the PI or known allergy or hypersensitivity to any of the components of the IP.
11. History of malignancy, except for non-melanoma skin cancer, excised more than 2 years ago and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to Screening.
12. A personal history of unexplained blackouts or fainting or known risk factors for Torsade de Pointes (eg, hypokalemia, heart failure).
13. Abnormal 12-lead ECG findings at Screening that are considered by the PI to be clinically significant, including arrhythmias or marked QT interval abnormalities (QTcF < 300 msec or ≥ 450 msec at Screening).
14. Confirmed (eg, 2 consecutive triplicate measurements) average systolic blood pressure (SBP) > 140 or < 90 mmHg, and diastolic blood pressure (DBP) > 90 or < 45 mmHg at Screening.
15. Confirmed (eg, 2 consecutive triplicate measurements) average resting HR > 100 or < 45 beats per minute at Screening.
16. Vaccination with a live vaccine within the 4 weeks prior to Screening or that is planned within 4 weeks of dosing, and any non-live vaccination within the 2 weeks prior to Screening, or that is planned within 2 weeks of dosing or planned during study participation (including vaccines for COVID-19).
17. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening.
18. Participants with a positive toxicology screening panel (urine test including qualitative identification of barbiturates, tetrahydrocannabinol [THC], amphetamines, benzodiazepines, opiates, cocaine, and cotinine), or alcohol breath test at Screening or Day -1.
19. Participants with a history of substance abuse or dependency or history of recreational intravenous (IV) drug use over the last 6 months (by self-declaration).
20. Use of any IP or medical device within 30 days prior to screening.
21. Use of any prescription drugs for 14 days prior to dosing or over the counter medication, herbal remedies, supplements or vitamins 7 days prior to dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose Cohort A1; Subjects will receive a single dose of either dose level 1 of HH-120 or placebo	Drug: Placebo; Placebo to match; Biological: HH-120 Dose 1; Dose level 1 of HH-120; Other Names: HH-120
Experimental: Single Ascending Dose Cohort A2; Subjects will receive a single dose of either dose level 2 of HH-120 or placebo	Drug: Placebo; Placebo to match; Biological: HH-120 Dose 2; Dose level 2 of HH-120; Other Names: HH-120
Experimental: Single Ascending Dose Cohort A3; Subjects will receive a single dose of either dose level 3 of HH-120 or placebo	Drug: Placebo; Placebo to match; Biological: HH-120 Dose 3; Dose level 3 of HH-120; Other Names: HH-120
Experimental: Multiple Ascending Doses Cohort B1; Subjects will receive multiple doses of either Dose level 1of HH-120 or placebo	Drug: Placebo; Placebo to match; Biological: HH-120 Dose 1; Dose level 1 of HH-120; Other Names: HH-120
Experimental: Multiple Ascending Doses Cohort B2; Subjects will receive multiple doses of either Dose level 2 of HH-120 or placebo	Drug: Placebo; Placebo to match; Biological: HH-120 Dose 2; Dose level 2 of HH-120; Other Names: HH-120
Experimental: Multiple Ascending Doses Cohort B3; Subjects will receive multiple doses of either Dose level 3 of HH-120 or placebo	Drug: Placebo; Placebo to match; Biological: HH-120 Dose 3; Dose level 3 of HH-120; Other Names: HH-120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment emergent adverse events (TEAEs)	An Adverse Event (AE) is any event, side-effect or any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE that started on or after the first study treatment or that worsened after the first study treatment will be regarded as TEAEs.	Day 1- Day 15 (SAD) or Day 22 (MAD)
Severity of treatment emergent adverse events (TEAEs)as assessed by CTCAE v5.0	An Adverse Event (AE) is any event, side-effect or any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE that started on or after the first study treatment or that worsened after the first study treatment will be regarded as TEAEs.	Day 1- Day 15 (SAD) or Day 22 (MAD)
Duration of treatment emergent adverse events (TEAEs)	An Adverse Event (AE) is any event, side-effect or any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE that started on or after the first study treatment or that worsened after the first study treatment will be regarded as TEAEs.	Day 1- Day 15 (SAD) or Day 22 (MAD)
Number of participants with serious adverse events (SAEs)	A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of IP (active or placebo) that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect	Day 1- Day 15 (SAD) or Day 22 (MAD)
Severity of serious adverse events (SAEs) as assessed by CTCAE v5.0	A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of IP (active or placebo) that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect	Day 1- Day 15 (SAD) or Day 22 (MAD)
Duration of serious adverse events (SAEs)	A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of IP (active or placebo) that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect	Day 1- Day 15 (SAD) or Day 22 (MAD)
Number of participants with abnormal clinically significant physical examination findings	Complete and symptom directed physical examination will be performed	Day 1- Day 15 (SAD) or Day 22 (MAD)
Number of participants with abnormal clinically significant electrocardiogram (ECG)	Single resting 12- lead ECGs will be collected	Day 1- Day 15 (SAD) or Day 22 (MAD)
Number of participants with clinically significant change in vital signs from baseline	Vital signs include heart rate, blood pressure, respiratory rate and tympanic temperature	Day 1- Day 15 (SAD) or Day 22 (MAD)
Changes in the spirometry score from Baseline	Measured by Forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) after dosing	Day 1- Day 15 (SAD) or Day 22 (MAD)
Number of participants with abnormal clinically significant clinical laboratory parameters	Clinical laboratory test include hematology, coagulation, biochemistry and urinalysis	Day 1- Day 15 (SAD) or Day 22 (MAD)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax in SAD and MAD	Maximum observed HH-120 concentration	Day 1- Day 15 (SAD) or Day 22 (MAD)
Tmax in SAD and MAD	Time to the maximum observed HH-120 concentration	Day 1- Day 15 (SAD) or Day 22 (MAD)
t1/2 in SAD and MAD part	Terminal elimination half life calculated as ln (2)/λz	Day 1- Day 15 (SAD) or Day 22 (MAD)
AUC0-last	Area under the plasma concentration-time curve from time zero (from the start of inhalation time) to the last time point with measurable analyte concentration	Day 1- Day 15 (SAD) or Day 22 (MAD)
AUC0-inf	AUC from time zero (from the start of inhalation time) extrapolated to infinity	Day 1- Day 15 (SAD) or Day 22 (MAD)
%AUCextrap	The percentage of the AUC that has been extrapolated beyond the last observed data point	Day 1- Day 15 (SAD) or Day 22 (MAD)
Kel or λz	Apparent terminal elimination rate constant, calculated by linear regression of the terminal linear portion of the log concentration vs time curve	Day 1- Day 15 (SAD) or Day 22 (MAD)
CL/F	Apparent total body clearance	Day 1- Day 15 (SAD) or Day 22 (MAD)
Vz/F in SAD	Apparent volume of distribution during the terminal phase	Day 1- Day 15 (SAD) or Day 22 (MAD)
CL/Fss in MAD	Apparent total plasma clearance at steady state	Day 1-Day 22
Vz/Fss in MAD	Apparent terminal volume of distribution at steady state	Day1- Day 22
Accumulation ratio (RA)	AUC0-24 hours on Day 7/AUC0-24 hours on Day 1	Day 1- Day 7
Immunogenicity of HH-120	To determine the presence and levels of anti-drug antibody (ADA).	Day 1- Day 15 (SAD) or Day 22 (MAD)

Collaborators and Investigators

• Sponsor: Huahui Health
• Investigators: Study Director: Yongqing Lin, Huahui Health Ltd

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): May 26, 2022
• Study Completion (Actual): August 2, 2022

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections
• Other Study ID Numbers: HH120-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No