The overall objective of this trial is to evaluate the concept of pharmacological activity of BI 767551 in non-hospitalized patients with mild to moderate COVID-19 symptoms and to identify a potentially efficacious and safe dose regimen from Phase…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint in Phase II is the time-weighted change from baseline in
viral shedding over 8 days (in site collected) nasopharyngeal swabs by RT-qPCR,
defined as a change from baseline in log10 viral load. Refer to Section 7.2.3
of the protocol for further details.
The primary endpoint in Phase III is hospitalization or death from any cause by
Day 29.
Secondary outcome
The secondary endpoints in Phase II are:
* Time-weighted change from baseline in viral shedding over 29 days in site
collected NP
swabs by RT-qPCR, defined as a change from baseline in log10 viral load.
* Loss of detection of SARS-CoV-2 RNA by site collected NP swab at Day 4, 8,
15, 22
and 29.
2.1.3.2 Secondary endpoints in Phase III
The secondary endpoints in the Phase III are:
* Time to death over 29 days
* Hospitalization by Day 29
* Hypoxia or hospitalization or death from any cause by Day 29
* Hypoxia by Day 29
* Time to clinical improvement over 29 days, defined as the time to either an
improvement
of two points on the 11-point WHO Clinical Progression Scale or a score of 0 on
the
Clinical Progression Scale, whichever comes first.
* Time to loss of detection of SARS-CoV-2 RNA by site collected NP swabs over
29 days
Background summary
People with mild to moderate COVID-19 symptoms may benefit from treatment with
BI 767551 by reducing the risk of worsening the condition, reducing
hospitalization or death.
We think that BI 767551 can help the body prevent further virus uptake and
break down the virus more quickly.
Study objective
The overall objective of this trial is to evaluate the concept of
pharmacological activity of BI 767551 in non-hospitalized patients with mild to
moderate COVID-19 symptoms and to identify a potentially efficacious and safe
dose regimen from Phase II part to take into the Phase III part.
The Phase II part of the trial will aim to prove the concept of pharmacological
activity of different dose levels of BI 767551 i.v. in comparison to placebo
and to identify efficacious and safe dose regimens in non-hospitalized patients
with mild to moderate COVID-19 symptoms.
The Phase II part of the trial will support the decision on whether to move to
Phase III and which i.v. dose to take to the Phase III part of the study. The
lowest efficacious dose showing adequate viral clearance with an acceptable
safety profile will be taken into Phase III. The inhaled route administration
is further evaluated in a different confirmatory trial conducted by NIAID
(ACTIV-2).
The Phase III part of the trial will aim to confirm efficacy, safety and
tolerability of the dose regimen of BI 767551 selected from the Phase II part
in comparison to placebo in non-hospitalized patients with mild to moderate
COVID-19 symptoms.
Study design
This is a Phase II/III seamless, randomised, double-blind, placebo controlled,
parallel group, group-sequential study
Intervention
In the Phase II part, the study medication.is administered via an infusion
(i.v.) or by inhalation.
The i.v. dose is dependent on the weight of the patient, and the dose for
inhalation (nebulized) is fixed with the following treatment arms:
* Placebo i.v. + Placebo inhaled
* BI 767551 i.v. 10 mg/kg + Placebo inhaled
* BI 767551 i.v. 40 mg/kg + Placebo inhaled
* Placebo i.v. + BI 767551 250 mg inhaled
In Phase III, the medication will be administered via i.v as a fixed dose with
the following
potential treatment arms:
* BI 767551 i.v. 700 mg or 2800 mg
* Placebo
Study burden and risks
Burden:
Patients eligible for this study are not admitted to the hospital for their
COVID-19 infection. So if a patient chooses to participate in this study, they
will have to come to the hospital for study visits which are all extra. Of the
10 visits 2 may be done remotely. Additionally, extra assessments will be done:
- 11-point WHO Clinical Progression Scale 9x
- Physical examination: 6x
- COVID-19 test at site: nasofarynx (nose)swab 6x
- COVID-19 test at site: orofarynx (throat)swab 6x
- COVID-19 test at home nasofarynx (nose)swab 11x
- Vital functions (blood pressure, heart rate, temperature, respiratory rate):
7x
- Blood draws: 7x
- Urine collection 5x
- Pregnancy test (if applicable): 6x
The patients are also asked to maintain a diary to document the symptoms they
are experiencing from day 2-29. They also will document their temperature and
oxygen saturation values in this diary.
Risks:
Risks of adverse reactions or allergic reaction to study medication.
Risks of adverse reactions to study procedures, such as bruising after
venapunction.
Comeniusstraat 6
Alkmaar 1817MS
NL
Comeniusstraat 6
Alkmaar 1817MS
NL
Listed location countries
Age
Inclusion criteria
1. * 18 years old, males and females.
2. Signed and dated written informed consent in accordance with ICH-GCP and
local legislation prior to admission to the trial.
3. Documentation of laboratory-confirmed SARS-CoV-2 infection, as determined by
a molecular test (antigen or nucleic acid) from any respiratory tract specimen
(NP or nasal swab or saliva) collected no more than 72 hours prior to start of
treatment.
4. Patients experienced mild to moderate COVID-19-related symptoms or measured
fever for no more than 5 days prior to start of treatment where symptoms are
defined by fever, feeling feverish, fatigue, cough, shortness of breath at rest
or during activity, sore throat, body pain or muscle pain/ aches, chills,
headache, nasal obstruction or congestion, loss of smell or taste, nausea,
diarrhea, vomiting, or dysgeusia.
5. One or more of the following signs/symptoms present on day of start of
treatment: fever, feeling feverish, fatigue, cough, shortness of breath at rest
or during activity, sore throat, body pain or muscle pain/ aches, chills,
headache, nasal obstruction or congestion, loss of smell or taste, nausea,
diarrhea, vomiting, or dysgeusia.
6. Women of childbearing potential (WOCBP) and men able to father a child must
be ready and able to use highly effective methods of birth control per ICH M3
(R2) that result in a low failure rate of less than 1% per year when used
consistently and correctly.
Exclusion criteria
1. Body weight of less than 40 kg.
2. Severe or critical COVID-19 including at least one of:
o Oxygen saturation (SpO2) * 93 % on room air or on their usual level of oxygen
supplementation in case of chronic oxygen use
o Ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to
fractional inspired oxygen (FiO2) < 300 (in case arterial blood sample was
taken)
o Respiratory rate * 30/min or heart rate * 125/min. Measure should be obtained
at rest by study staff within 24 hours of start of treatment.
o History of hospitalization for COVID-19
o Current or imminent need for hospitalization or immediate medical attention
in the clinical opinion of the site investigator. Does not include patients
hospitalized for isolation only.
3. Receipt of intraveneous immunoglobulin within 12 weeks prior to Visit 2.
4. Receipt of COVID-19 convalescent plasma treatment at any time prior to Visit
2.
5. Receipt of any SARS-CoV-2 monoclonal antibody treatment at any time prior to
Visit 2.
6. Receipt of SARS-CoV-2 vaccine at any time prior to Visit 2.
7. Receipt of an investigational product for COVID-19 within 5 half-lives prior
to Visit 2.
8. Receipt of systemic steroids (e.g. prednisone, dexamethasone) within 4 weeks
prior to Visit 2 unless used for chronic condition (see Section 4.2.2.1).
9. Patients who must or wish to continue the intake of restricted medications
or any drug considered likely to interfere with the safe conduct of the trial.
10. Any co-morbidity requiring surgery within 7 days prior to study entry, or
that is considered life threatening in the opinion of investigator within 30
days prior to study entry.
11. Have any serious concomitant systemic disease, condition or disorder that,
in the opinion of the investigator, should preclude participation in this study.
12. Patients not expected to comply with the protocol requirements or not
expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse
or any other condition that, in the investigator*s opinion, makes the patient
an unreliable trial participant).
13. Currently enrolled in any other type of medical research judged not to be
compatible with this study.
14. Known allergy/sensitivity or any hypersensitivity to any of the components
used in the formulation of the interventions.
15. Previous enrolment in this trial. Patients participating in Phase II are
not eligible for Phase III. Re-screening is allowed once, for repeat of RT-qPCR
or antigen SARS-CoV-2 test, if required. The test method used for initial
screening (RT-qPCR or antigen) should be used for re-screening.
16. Women who are pregnant, nursing, or who plan to become pregnant while in
the trial.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-005588-29-NL |
| ClinicalTrials.gov | NCTnummernognietbekend |
| CCMO | NL77209.078.21 |