A First-in-Human Study in Adult Subjects Hospitalized with Covid-19 to Investigate a new product called ARGX-117

• Register: EUCTR
• Last refreshed on: 17 May 2021
• Main ID: EUCTR2020-001546-19-BE
• Date of registration: 09/04/2020
• Prospective Registration: Yes
• Primary sponsor: argenx BV
• Public title: A First-in-Human Study in Adult Subjects Hospitalized with Covid-19 to Investigate a new product called ARGX-117
• Scientific title: A First-in-Human Study in Adult Subjects Hospitalized with Covid-19 to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Efficacy of ARGX-117
• Date of first enrolment: 21/04/2020
• Target sample size: 6
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-001546-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium

Contacts

• Name: Regulatory
• Affiliation: argenx BV

• Name: Regulatory
• Affiliation: argenx BV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female and at least 18 years of age, inclusive, on the day that the informed consent form (ICF) is signed. Subjects older than 75 years must have a clinical frailty score of 1, 2 or 3 before hospitalization for COVID-19 infection (Appendix 6).
2. COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 (within 4 weeks prior to first dose administration)
For part B and C of the trial only: in some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis prior to first dose administration because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion.
3. Is in a specialized COVID-19 ward
4. Part A only:
First symptoms suggestive for COVID-19 infection appeared at least 12 days prior to dosing on day 1
Presents with PaO2/FiO2 >350 mmHg while breathing ambient air in an upright position
Is recovering from COVID-19 infection as demonstrated by declining CRP levels preceding the first dose per judgement of the investigator
5. Part B and part C only:
• Presents with bilateral infiltrates (within 48 hours of screening) on chest X-ray or CT scan
• First symptoms suggestive of COVID-19 infection appeared between 6 and 16 days prior to dosing on day 1
• Presents with hypoxemia as defined by PaO2/FiO2 <350 mmHg while breathing ambient air in an upright position
6. All female subjects must have a negative serum pregnancy test at screening.
7. All female subjects of childbearing potential for at least 1 month before dosing on day 1 have been on a stable regimen of at least one highly effective method of contraception (ie, failure rate of less than 1% per year) during the study and for 90 days after the last administration of ARGX-117
8. Nonvasectomized male subjects who are sexually active with female partners of childbearing potential: must agree to use condoms during every penile-vaginal intercourse for the entire duration of the study and up to 90 days after the last ARGX-117 administration.
The female partner of childbearing potential of a nonvascetomized male subject will be required to use an adequate form of contraception.
9. Male subjects must agree not to donate semen until 90 days after the last ARGX-117 administration.
10. Body mass index (BMI) between 18-40 kg/m2, inclusive, at screening.
11. Understands the purpose and risks of the study, will be available for all study visits, and will provide signed and dated informed consent prior to any study-related procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
1. Known hypersensitivity to one of the components of the ARGX-117, or a history of a significant allergic reaction to any drug, per judgement of the investigator
2. Known active hepatitis B or C infection or a known human immunodeficiency virus infection
3. History of severe allergic or anaphylactic reactions
4. Receiving high dose systemic steroids (>8 mg methylprednisolone or equivalent for more than 1 month) for a disorder unrelated to COVID-19 infection
5. Admitted to a specialized COVID-19 ICU
6. Receiving mechanical ventilation longer than 24 hours prior to screening
7. Known history or any symptoms of a clinically significant illness in the 6 months before the first ARGX-117 administration that could put the subject at unacceptable risk per judgement of the investigator
8. Clinically significant active or chronic bacterial, viral – except COVID-19 – or fungal infection at screening that could put the subject at unacceptable risk per judgement of the investigator
9. Presents with abnormal laboratory parameter result at screening that may confound the data or pose a clinically significant safety risk for the subject per judgement of the investigator
10. Estimated glomerular filtration rate <60 mL/min/1.73 m² as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
11. History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for =3 years before the first administration of the ARGX-117. Subjects with the following cancer can be included at any time:
• Adequately treated basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
12. Known genetic deficiencies for the complement cascade system
13. Clinically relevant abnormalities detected on the ECG regarding either rhythm or conduction. A first-degree heart block or sinus arrhythmia will not be considered a significant abnormality
14. Used an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the ARGX-117
15. Is unlikely to survive longer than 7 days
16. Is an investigator, sub-investigator, research assistant, pharmacist, study coordinator, or other staff or a relative who is directly involved in the conduct of the study.
17. Any condition or circumstance that in the opinion of the investigator may make a subject unlikely or unable to complete the study or comply with study procedures and requirements



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

PCR-confirmed Covid-19 infection

Intervention(s)

Product Name: ARGX-117
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ARGX-117
Other descriptive name: ARGX-117
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of ARGX-117 IV administered in adult subjects initially hospitalized with COVID-19 infection

In part B and part C of the trial the primary objectives will be to investigate efficacy and safety of ARGX-117 IV administered in subjects initially hospitalized with Covid-19

Secondary Objective: 1. To investigate the pharmacokinetics (PK) of ARGX-117 IV administered in differing dose regimens in subjects initially hospitalized with Covid-19
2. To investigate the pharmacodynamics (PD) and immunogenicity (ADA) effects of ARGX-117 IV administered in differing dose regimens in subjects initially hospitalized with Covid-19
3. To investigate the preliminary efficacy of ARGX-117 IV administered in differing dose regimens in subjects initially hospitalized with Covid-19

Primary end point(s): The safety and tolerability of ARGX-117 will be assessed by the totality of safety and tolerability data, including incidence and frequency of AEs and SAEs; vital sign results; physical examination findings; ECG recordings; and clinical laboratory tests (routine hematology, clinical chemistry, and urinalysis), and specialty laboratory testing (CRP, ferritin, procalcitonin, D-dimer, cytokine panel).

Timepoint(s) of evaluation of this end point: Safety will be continuously monitored until end of study
other endpoints D1 until D4, D6, D8, D15, D22, D29, D36, D50, D64, D92 or end of study

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: D1 until D4, D6, D8, D15, D22, D29, D36, D50, D64, D92 or end of study

Secondary end point(s): • PK parameters of ARGX-117: single-dose, dose normalized
• PD markers: free C2 concentration, total C2 concentration, and CH50
• Incidence of ADA subject status to ARGX-117
• Efficacy endpoints
? Clinical status according to the Ordinal scale (Appendix 6)
? Duration hospitalization since first treatment with ARGX-117
? Time to progression to invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) since first treatment with ARGX-117
? Time to progression to high-flow oxygen device since first treatment with ARGX 117
? Time to hospital discharge since first treatment with ARGX-117

Secondary ID(s)

ARGX-117-2001

Source(s) of Monetary Support

argenx BV

Ethics review

Status: Approved
Approval date: 20/04/2020
Contact: