Clinical trial NCT05069610: Evaluating Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adults With Mild to Moderate COVID-19
Official title: A Parallel Treatment, Phase 2a, Double-blind, Randomized, Placebo-controlled, 4-arm Study to Evaluate the Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adult Aged 20 to 70 Years With Mild to Moderate COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Keywords: SARS-CoV-2
COVID-19
Therapy, viral clearance, immunomodulator, IFN, innate
Lead sponsor: Advagene Biopharma Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2021-10-06
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: AD17002 has demonstrated superior safety and efficacy as a nasal adjuvant function to an influenza vaccine in two completed clinical studies, and has innate immune modulatory and anti-inflammatory properties which could potentially be an effective treatment for SARS-CoV-2 infection.

This Phase 2a, multi-center study is set up to assess the safety, tolerability, and potential efficacy of AD17002 in participants with mild to moderate COVID-19. The Immunogenicity of repeated doses of AD17002 will also be explored.

Detailed description: AD17002 has demonstrated superior safety and efficacy as a nasal adjuvant function to an influenza vaccine in two completed clinical studies and has innate immune-modulatory and anti-inflammatory properties which could potentially be an effective treatment for SARS-CoV-2 infection.

This Phase 2a, multi-center study is set up to assess the safety, tolerability, and potential efficacy of AD17002 in participants with mild to moderate COVID-19. The cycle threshold (Ct) was used as a surrogate biomarker for viral clearance in the exploratory study.

The COVID-19 pandemic has led to significant mortality in global populations and suppression of the economy. The prompt development of the vaccine for SARS-CoV-2 represents an unprecedented achievement for mankind, nevertheless, the unstoppable transmission of the virus highlights human's insufficient and lack of preparedness in mucosal immunity, which acts as the port of entries to not just SARS-CoV-2, but many viruses.

The AD17002, also known as LTh(αK), is an immunomodulator, which induces expression of type I and III interferons (IFN-I/III) from mucosal epithelial cells. The IFN-I/III are critical components to innate immunity, the first line defender against infection, and modulator and initiator of adaptive immunity. The IFN-I is antagonized by many SARS-CoV-2 viral proteins and studies have shown the association between IFN-I deficiency and severe COVID-19. In this study, we intended to treat subjects with AD17002, which induced nasal epithelial cells to express IFN-I/III.

Participants who meet the eligibility criteria will be isolated and confined to the study site to receive treatment for COVID-19. Eligible participants will be assigned to 2 cohorts, Cohort 1 and Cohort 2, sequentially. Cohort 1 will receive 3 doses of AD17002 or placebo weekly, while Cohort 2 will receive 3 doses of LTh(αK) or placebo every other day (Days 1, 3, and 5). Within each cohort, participants will be randomized in a 2:1 ratio to receive standard-of-care treatment and add-on therapy of AD17002 at 20 μg or placebo. Randomized participants will be assigned a participant number. The participants, site personnel, and the Sponsor will be blinded to the treatment assignment. Randomization will not be stratified and participants who withdraw from the study after starting treatment will not be replaced, except for participants who undergo sentinel dosing in Cohort 2.

Eligibility criteria: Inclusion Criteria:

1. Aged ≥ 20 and ≤ 70 years
2. SARS-CoV-2 infection confirmed by real-time RT-PCR ≤ 4 days before randomization.
3. Symptoms of mild to moderate illness with COVID-19 at Screening. At least one key COVID-19 symptom should have a score of 2 or higher using the scoring system in the diary card, with the exception of fever, sense of smell, and sense of taste where participants may be enrolled with a score of 1 or higher.
4. Have a negative serum pregnancy test at Screening (for female participants of childbearing potential). A female participant who is of childbearing potential agrees to remain abstinent or use (or have their partner use) two acceptable methods of birth control within the projected duration of the study. Acceptable methods of birth control are: intrauterine device, hormonal contraception, diaphragm with spermicide, contraceptive sponge, condom, vasectomy, as per local regulations or guidelines.
5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5-fold of upper limit of normal (ULN) and total bilirubin ≤ 1.5-fold of ULN.
6. Creatinine clearance ≥ 50 mL/min.
7. A female participant who is not of childbearing potential is eligible without requiring the use of contraception. A female participant who is not of childbearing potential is defined as one who has either:

   1. Reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels in the postmenopausal range as determined by the laboratory, or 12 months of spontaneous amenorrhea), or
   2. At least six weeks postsurgical documented total hysterectomy and/or bilateral salpingo-oophorectomy, or
   3. Bilateral tubal ligation
8. Participant or the participant's legal representative understands the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
9. Provide written informed consent for the study and willing to adhere to dose regimen and visit schedules.

Exclusion Criteria:

1. Participant has clinical signs suggestive of moderate (pneumonia) or more severe illnesses with COVID-19 (as defined in the Taiwan CDC "Interim Guideline for Clinical Management of SARS-CoV-2 Infection Version 13" (Taiwan CDC, Clinical Management of SARS-CoV-2 Infection).
2. Participation in any other clinical study of an investigational agent treatment for SARS- CoV-2 infection within 30 days prior to the first IMP dosing.
3. Participant who has a history of confirmed SARS-CoV-2 infection.
4. Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 \< 24 hours prior to the first IMP dosing.
5. History of severe renal disease (treatment with dialysis or phosphate binders) or clinically apparent hepatic impairment (e.g., jaundice, cholestasis, hepatic synthetic impairment, active hepatitis).
6. Impaired cardiac function or clinically significant cardiac diseases as judged by the Investigator.
7. History of anaphylaxis reaction to any known or unknown cause.
8. Immunosuppressed persons as result of illness (e.g., HIV infection) or treatment.
9. Documented history of Bell's palsy.
10. History of allergic reaction to kanamycin.
11. Immunosuppressive treatment within 3 months prior to the Screening Visit.
12. Ongoing treatment with any specific immunotherapy at the time of the Screening Visit.
13. Assessed by the Investigator to be ineligible to participate in the study.

Primary outcomes:
measure: The proportion of participants who experience adverse events
timeFrame: 7 weeks
measure: The proportion of participants with treatment-emergent adverse events (TEAE) leading to investigational medicinal products (IMPs) discontinuation
timeFrame: 7 weeks
measure: The nasal tolerability to investigational medicinal products (IMPs)
timeFrame: 7 weeks
Secondary outcomes:
measure: The time to proportions of participants have a Ct≥30
timeFrame: 7 weeks
measure: Time to recovery* of fever (days)
timeFrame: 7 weeks
measure: Time to recovery* of sore throat (days)
timeFrame: 7 weeks
measure: Time to recovery* of cough (days
timeFrame: 7 weeks
measure: Time to recovery* of fatigue (days).
timeFrame: 7 weeks
measure: Time to recovery* of muscle/body pain (days)
timeFrame: 7 weeks
measure: Time to recovery* of other symptoms (days)
timeFrame: 7 weeks
measure: The mean change from baseline to each specified time point on National Early Warning Score 2 (NEWS2)
timeFrame: 7 weeks
Other outcomes:
measure: Changes to anti-SARS CoV-2 antibody titers from baseline
timeFrame: 7 weeks
measure: Changes to pre-specified immunological markers
timeFrame: 7 weeks
measure: Viral genome integrity analysis
timeFrame: Cohort 1, 3 weeks; Coohort 2, 8 days
Locations:
city: Taipei
country: Taiwan
facility: Advagene Biopharma
city: Taoyuan
country: Taiwan
facility: Chang Gun Medical Foundation
Study officials:
affiliation: Advagene Biopharma
name: Mingi Chang, PhD
role: STUDY_DIRECTOR
References: