We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled APN01 Developed as Treatment for COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05065645
Recruitment Status : Completed
First Posted : October 4, 2021
Last Update Posted : September 23, 2022
Sponsor:
Collaborator:
Apeiron Respiratory Therapies GmbH
Information provided by (Responsible Party):
Apeiron Biologics

Brief Summary:

APN01 is a soluble recombinant form of the human angiotensin-converting enzyme 2 (rhACE2) that is currently under development as a therapy for corona-virus-disease 2019 (COVID-19). By effectively mimicking ACE2 within the body, APN01 is designed to block the SARS-CoV-2 from binding to the ACE2 receptor and infecting cells while at the same time downregulating the renin-aldosterone-angiotensin system (RAAS) to help prevent inflammation and organ injury - critical components involved in the cytokine storm response. ACE2 is the key entry receptor for the SARS-CoV-2. Competitive binding by exogenous angiotensin-converting enzyme 2 (ACE2) may block viral entry, thereby decreasing viral replication in ACE2 expressing organs and protecting the lungs and distal organs from injury induced by SARS-CoV-2.

APN01 has been developed as an IV agent to treat acute lung injury and pulmonary arterial hypertension, and moderate to severe COVID-19 infection. Encouraged by the favorable safety profile of IV APN01, we have developed the nebulized APN01 formulation to deliver the drug directly to the respiratory tract, where the virus is mainly found, decreasing systemic exposure and increasing local pulmonary concentration. APN01 intravenously and as inhalation in preclinical studies has been well tolerated with no overall difference in clinical studies from placebo in human trials to date.

This study will investigate nebulized APN01 safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity before stepping forward in proof-of-concept studies in patients with COVID-19.


Condition or disease Intervention/treatment Phase
Covid19 Drug: Angiotensin Converting Enzyme 2 Drug: Sodium chloride Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I, Double-blind, Placebo-controlled, Dose-escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Inhaled APN01
Actual Study Start Date : October 19, 2021
Actual Primary Completion Date : May 27, 2022
Actual Study Completion Date : May 27, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: APN01
Angiotensin Converting Enzyme 2: 1.25 mg/ml, 2.5 mg/ml or 5 mg/ml
Drug: Angiotensin Converting Enzyme 2
SAD: single dose; MAD: dosage 2x daily for 7 days
Other Name: Inhalation solution

Placebo Comparator: NaCl
Sodium Chloride: 0.9% NaCl solution
Drug: Sodium chloride
SAD: single dose; MAD: dosage 2x daily for 7 days
Other Name: Inhalation solution




Primary Outcome Measures :
  1. Adverse events [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Incidence of adverse events (AEs), serious AEs (SAEs), study withdrawals due to AEs, adverse drug reactions (ADRs), and all-cause death,

  2. Vital signs: Supine blood pressure assessed by systolic and diastolic blood pressure in mmHg [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Systolic and diastolic blood pressure in mmHg

  3. Vital signs: Resting pulse rate measured in beats per minute [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Resting pulse rate measured in beats per minute

  4. Vital signs: Body temperature assessed contactless via TriTemp thermometer in degree C [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Body temperature measured in degree C

  5. Vital signs: Respiratory rate measured in breaths/min [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Respiratory rate measured in breaths/min

  6. Vital signs: Peripheral oxygen saturation (SaO2) measured in % [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Peripheral oxygen saturation (SaO2) measured in %

  7. Clinical laboratory tests: Clinically significant changes of hematology, clinical chemistry and coagulation assessed via blood sample collection [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Clinically significant changes of hematology, clinical chemistry, coagulation and urinalysis assessed via blood sample collection

  8. Clinical laboratory tests: Clinically significant changes of urinalysis measurement assessed via urin collection [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Clinically significant changes of urinalysis measurement assessed via urin collection

  9. Physical examination: Abnormal findings of the general appearance [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of general appearance

  10. Physical examination: Abnormal findings of the ears [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the ears

  11. Physical examination: Abnormal findings of the nose [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the nose

  12. Physical examination: Abnormal findings of the head [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the head

  13. Physical examination: Abnormal findings of the eyes [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the eyes

  14. Physical examination: Abnormal findings of the dermatologic system [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the dermatologic system

  15. Physical examination: Abnormal findings of the mouth/throat/neck [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the mouth/throat/neck

  16. Physical examination: Abnormal findings of the thyroid [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the thyroid

  17. Physical examination: Abnormal findings of the lymph nodes [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the lymph nodes

  18. Physical examination: Abnormal findings of the respiratory system [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the respiratory system

  19. Physical examination: Abnormal findings of the cardiovascular system [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the cardiovascular system

  20. Physical examination: Abnormal findings of the gastrointestinal system [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the gastrointestinal system

  21. Physical examination: Abnormal findings of the extremities [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the extremities

  22. Physical examination: Abnormal findings of the musculoskeletal system [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the musculoskeletal system

  23. Physical examination: Abnormal findings of the neurologic system [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the neurologic system

  24. Physical examination: Abnormal findings of the psychiatric system [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Abnormal findings of the psychiatric system

  25. Heart function: QT interval corrected for heart rate (QTc) (Bazett's correction [QTcB]) in msec assessed via Twelve lead ECG [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Twelve lead ECG: QT interval corrected for heart rate (QTc) (Bazett's correction [QTcB]) measured in msec

  26. Pulmonary function assessed via Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) measured in L by spirometry [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) measured in L

  27. Pulmonary function assessed via Peak expiratory flow (PEF) measured in L/s by spirometry [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Peak expiratory flow (PEF) measured in L/s

  28. Pulmonary function assessed via FEV1/FVC ratio measured in % by spirometry [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    FEV1/FVC ratio measured in %

  29. Pulmonary function assessed via Total lung capacity (TLC) and Residual volume (RV) measured in L by body plethysmography [ Time Frame: SAD cohort: 2 weeks, MAD cohort: 3 weeks ]
    Total lung capacity (TLC) and Residual volume (RV) measured in L

  30. Fractional Exhaled Nitric Oxide (FeNO) levels measured in parts per billion (ppb) - in MAD cohort only [ Time Frame: MAD cohort: 3 weeks ]
    Fractional Exhaled Nitric Oxide (FeNO) levels measured in parts per billion (ppb)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy males and females between 18 to 55 years of age, inclusive, at the screening visit.
  2. Subject voluntarily agrees to participate in this study and signs an Ethics Committee approved informed consent prior to performing any of the screening visit procedures.
  3. Subject is able to understand and is willing to comply with all study requirements, and willing to follow the instructions of the study staff.
  4. Women of childbearing potential must have a negative pregnancy test, should not be breastfeeding, and must be willing to use highly effective methods of contraception for at least 1 month before, while participating in this study and until 1 month after the end of the treatment. The following terms of contraception apply:

    4.1. Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

    4.2. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study intervention. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.

    4.3. Sterilization of male partner (at least 6 months prior to Screening) with post-procedural semen specimen to verify a successful procedure (the report of the male partner will not be collected since the partner is not study participant). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.

    4.4. Placement of an intrauterine device or intrauterine system, or other forms of non-hormonal contraception that have comparable efficacy (failure rate <1%).

    4.5. Women who are postmenopausal are not required to use contraception. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range (FSH > 40 U/ml at Screening) must be used to confirm a postmenopausal state.

  5. Male subject must agree to stay abstinent or must use together with his female partner(s) use a form of highly effective contraceptive from the time of signing the informed consent form (ICF) until up to 3 months after receiving the study drug.
  6. Nonsmokers (and/or no use of other nicotine products during 1 year before screening visit).
  7. Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, at the screening visit.
  8. Healthy with no clinically significant findings, determined by medical evaluation (medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluations) at Screening.
  9. Forced expiratory volume in 1 second (FEV1) ≥80%.

Exclusion Criteria:

  1. Female subjects who are breastfeeding or female subjects with a positive pregnancy test at the screening visit or admission.
  2. Study participant has a history of an anaphylactic reaction to study drug or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
  3. Subject has used an investigational drug within 30 days (or 5 half-lives whichever is longer) prior to the first dose of study drug.
  4. Subject is on any regular (more than 4 days a week) prescription or nonprescription over the counter medication, topical medications, vitamins, dietary or herbal (occasional use of acetaminophen, paracetamol or ibuprofen allowed).
  5. Subject has positive urine test for drugs of abuse at the screening visit or admission.
  6. Regular consumption of alcohol within 6 months prior to Screening (> 7 drinks/week for females, > 14 drinks/week for males where 1 drink = 5 ounces [150 ml] of wine or 12 ounces [360 ml] of beer or 1.5 ounces [45 ml] of hard liquor), or use of illicit substances (such as marijuana) within 3 months prior to the screening visit.
  7. Subject has positive test for SARS-CoV-2 antigen or real-time RT-PCR, HBsAg, anti-HBc antibodies, HCV antibody, and/or HIV antibody at screening visit.
  8. Donation or loss of 450 ml or more of blood within 4 weeks or 250 ml of plasma within 4 weeks prior to initial dosing.
  9. Subject has a history or current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, hematologic, autoimmune, mental or other medical disorder, including cirrhosis or malignancy.
  10. Subject has a history of a psychiatric disorder that will affect the subject's ability to participate in the study as determined by the Investigator.
  11. Subject has a clinically relevant abnormal ECG.
  12. Subject has clinically relevant abnormal laboratory values at the discretion of the Investigator.
  13. Subject has hypertension with a mean systolic BP >150 mmHg or mean diastolic BP >100 mm Hg. Screening and admission tests may be repeated once if abnormal.
  14. Subject has acute, clinically significant illness within 30 days prior to admission, or any other condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study.
  15. Subject is an employee of the clinical research team (any APEIRON Biologics AG or study center employee).
  16. Subject is unable to understand the protocol requirements, instructions, study-related restrictions, nature, scope and possible consequences of the clinical study. Subject is unlikely to comply with the protocol requirements, instructions and study-related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits and improbability of completing the clinical study.
  17. Subject judged inappropriate as participant for the study by the Investigator for other reasons.
  18. Any signs of respiratory tract infection within 6 weeks of screening.
  19. Subject previously diagnosed with COVID-19 pneumonia.
  20. Presence of acute infection in the preceding 14 days, or presence of fever (> 37.9°C oral or tympanic temperature assessment), or acute symptoms of any severity on the scheduled date of admission.
  21. Subject who has a current bacterial, parasitic, fungal, or viral infection; any infection requiring hospitalization or intravenous antibiotics within 6 weeks prior to Screening.
  22. Subject has any pathological condition of the oro-laryngeal or respiratory tract that hinders use of nebulizer.
  23. Any of the following laboratory abnormalities:

    White blood cells, hemoglobin, platelets, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ±15% outside of normal limits. Alkaline phosphatase (ALP), urea and creatinine above 15% outside of normal limits.

  24. Subject has received or plans to receive a coronavirus vaccine, or any other vaccine, within 7 days prior to the first dose of study drug or during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05065645


Locations
Layout table for location information
Austria
Medical University of Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Apeiron Biologics
Apeiron Respiratory Therapies GmbH
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Apeiron Biologics
ClinicalTrials.gov Identifier: NCT05065645    
Other Study ID Numbers: APN01-01-INHAL
First Posted: October 4, 2021    Key Record Dates
Last Update Posted: September 23, 2022
Last Verified: February 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Pharmaceutical Solutions