A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects

NCT05453279 | Unknown Phase 1

• 1 other identifier: COV0001
• Study Type: interventional
• Target: 8
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will be a single center, Phase I, randomized, double-blind, placebo controlled, single and multiple ascending dose (SAD/MAD) study evaluating the safety, tolerability, and PK of Delcetravir after administration via oral inhalation in healthy subjects.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (20)

• Number of subjects with chest pain after single and multiple ascending doses of active and placebo comparator

  Symptoms of chest pain

  22 days

• Number of subjects with shortness of breath after single and multiple ascending doses of active and placebo comparator

  Symptoms of shortness of breath

  22 days

• Number of subjects with cough after single and multiple ascending doses of active and placebo comparator

  Symptoms of cough

  22 days

• Number of subjects with sputum production after single and multiple ascending doses of active and placebo comparator

  Symptoms of sputum production

  22 days

• Hemoglobin assessment after active comparator and placebo.

  Hemoglobin in g/L

  22 days

• White cell count assessment after active comparator and placebo.

  White cell count differential in 109/L

  22 days

• Platelet count assessment after active comparator and placebo.

  Platelet count in 109/L

  22 days

• Laboratory meaurement of sodium concentration after active comparator and placebo.

  Serum sodium in mmol/L

  22 days

• Laboratory measurement of potassium concentration after active comparator and placebo.

  Serum potassium in mmol/L

  22 days

• Laboratory measurement of bicarbonate concentration after active comparator and placebo.

  Serum bicarbonate in mmol/L

  22 days

• Laboratory measurement of urea concentration after active comparator and placebo.

  Serum urea in mmol/L

  22 days

• Laboratory measurement of creatinine concentration after active comparator and placebo.

  Serum creatinine in umol/L

  22 days

• Laboratory measurement of ALT concentration after active comparator and placebo.

  Serum ALT in U/L

  22 days

• Laboratory measurement of AST concentration after active comparator and placebo.

  Serum AST in U/L

  22 days

• Laboratory measurement of alkaline phosphatase concentration after active comparator and placebo.

  Serum alkaline phosphatase in U/L

  22 days

• Heart rate after active comparator and placebo.

  Heart rate in beats per minute

  22 days

• Blood pressure after active comparator and placebo.

  Systolic and diastolic blood pressure in mmHg

  22 days

• Respiratory rate after active comparator and placebo.

  Respiratory rate in breaths per minute

  22 days

• Pulse oximetry measurement after active comparator and placebo.

  Pulse oximetry in blood oxygen saturation

  22 days

• ECG after active comparator and placebo.

  PR interval, QRS complex, QTc interval

  22 days

Study Arms (2)

Active (experimental)

ACTIVE COMPARATOR

Delcetravir inhalation via dry powder inhaler device administered up to 4 single ascending doses. According to tolerability of single ascending doses, delcetravir is then given as inhalation via dry powder device in multiple ascending doses, once daily for 7 days.

Combination Product: Delcetravir dry powder inhaler

Placebo comparator

PLACEBO COMPARATOR

Placebo inhaler, identical in appearance to the active comparator, administered doses up to 4 single ascending doses. According to tolerability of single ascending doses, placebo doses are then given as inhalation via dry powder device in multiple ascending doses, once daily for 7 days.

Combination Product: Delcetravir dry powder inhaler

Interventions

Delcetravir dry powder inhaler COMBINATION_PRODUCT

Placebo dry powder inhaler

Active (experimental); Placebo comparator

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be included in the study:
• Male or female, non-smokers or casual smokers (defined as smoking the equivalent of less than an average of 5 cigarettes per week, and willing to abstain from smoking during involvement in the study), ≥18 and \<50 (For Parts A and B) or ≥50 and ≤80 (for Parts C and D) years of age, with BMI \>18.0 and \<32.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
• Healthy as defined by:
• the absence of clinically significant illness and surgery within 4 weeks prior to dosing.
• the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
• Females of childbearing potential who are sexually active with a male partner must be willing to use one of the following acceptable contraceptive methods throughout the study and for 30 days after the last study drug administration:
• Simultaneous use of intra-uterine device placed at least 4 weeks prior to study drug administration, and condom for the male partner;
• Simultaneous use of hormonal contraceptives started at least 4 weeks prior to study drug administration and condom for the male partner.
• Sterile male partner (vasectomized since at least 6 months).
• Females of non-childbearing potential must be:
• Post-menopausal (defined as absence of menses for at least 12 months prior to the first study drug administration) with confirmation of the post menopausal status by documented FSH level greater than 40 mIU/mL; or
• Surgically sterile (complete hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or tubal ligation at least 6 months prior to the first study drug administration).
• Male subjects who are not vasectomized for at least 6 months, and who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile) must be willing to use one of the following acceptable contraceptive methods from the first study drug administration until at least 90 days after the last study drug administration:
• a) Simultaneous use of a male condom and, for the female partner, hormonal contraceptives used since at least 4 weeks, or intra-uterine contraceptive device placed since at least 4 weeks;
• Male subjects who are sexually active with a same-sex partner must be willing to use a condom until study exit.

You may not qualify if:

• \) Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for HIV, hepatitis B, or hepatitis C found during medical screening.
• \) Any clinically significant illness, infection, medical/surgical procedure, or trauma within 4 weeks of check-in, or planned inpatient surgery or hospitalization during the study period.
• \) Any history of malignancy or neoplastic disease
• Positive urine drug screen, urine cotinine test, or alcohol breath test at screening.
• History of significant allergic reactions (e.g., drug reaction, anaphylactic reaction, hypersensitivity, angioedema) to any drug.
• Positive pregnancy test at screening.
• Clinically significant ECG abnormalities (QTc greater than 450 ms) or vital sign abnormalities (systolic blood pressure less than 90 or greater than140 mmHg, diastolic blood pressure less than 40 or greater than 90 mmHg, or heart rate less than 40 or greater than100 bpm, oxygen saturation less than 95% O2) at screening.
• History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit. Regular use of alcohol is defined as greater than 14 units of alcohol per week, where 1 unit is defined as 375 mL of beer at 3.5% a/v, 100 mL of wine at 13.5% a/v, or 30 mL of spirit at 40% a/v.
• History of drug abuse within 1 year prior to screening, recreational use of soft drugs (such as tetrahydrocannabinol \[THC\]) within 1 month prior to the screening visit, or hard drugs (amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methyledioxymethamphetamine \[MDMA\], and phencyclidine \[PCP\]) within 3 months prior to screening.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
• Use of medications for the timeframes specified below, with the exception of medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the PK profile of the study drug or subject safety (e.g., topical drug products without significant systemic absorption):
• Prescription medications (except for hormonal contraceptives) within 14 days prior to the first dosing;
• Over-the-counter products and natural health products (including herbal remedies, such as St. John's wort, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to the first dosing, with the exception of the occasional use of acetaminophen/paracetamol (up to 2 g/day), ibuprofen (up to 800 mg/day), and topical formulations without significant systemic absorption;
• Depot injection or implant (except for hormonal contraceptives) of any drug within 3 months prior to the first dosing.
• Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.

Sponsors & Collaborators

• Esfam Biotech Pty Ltd: lead

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Albert G Frauman, MD

  Esfam Biotech Pty Ltd

  STUDY DIRECTOR

Central Study Contacts

Albert G Frauman, MD

CONTACT

+61 416198042; albert@esfambiotech.com.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind allocation to inhalation formulation (active or placebo)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study will be a single center, Phase I, randomized, double-blind, placebo controlled, single and multiple ascending dose (SAD/MAD) study evaluating safety, tolerability, and PK after administration via oral inhalation in healthy subjects.

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: July 12, 2022
• Study Start: September 1, 2022
• Primary Completion: November 1, 2022
• Study Completion: January 1, 2023
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share