There have been reports of a more serious course of COVID-19 infections in patients with a reduced immune system, such as patients with congenital immune disorders, (haematological) malignancies or patients taking medications that suppress the…
ID
Source
Brief title
Condition
- White blood cell disorders
- Immunodeficiency syndromes
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The endpoint of this study is a severe course of disease, which is defined
until day 28 after randomization:
* Start of adjunctive ventilator support (HFNO, mechanical ventilation) or an
indication to do so but due to due to previously agreed treatment restrictions
HFNO or mechanical ventilation is not initiated..
* Admission to an intensive care unit for progression of respiratory
insufficiency..
* No clinical improvement on day 7 after randomization or any day thereafter
after first day of treatment (based on oxygen use in patients that require
oxygen and based on clinical disease burden (including fever) in patients that
require no oxygen).
* Readmission for COVID-19.
Secondary outcome
* Severity of COVID-19 disease in patients that have no anti SARS-CoV-2
antibodies upon inclusion (*per protocol* analysis).
* Duration of hospitalization.
* 28 days overall mortality.
* The four individual endpoints that compose the primary endpoint.
* Time to complete recovery from COVID-19 related symptoms.
* Rate of viral decay
* Development of long-term persistent neutralizing antibodies against SARS-COV-2
* T-cell immunity as measured by in vitro specific T cell response to COVID-19
tetrameric antigens.
Background summary
The COVID-19 pandemic has unfortunately caused many infections and deaths
around the world. COVID-19, the disease caused by infection with the SARS-CoV2
virus, can cause symptoms of varying degrees of severity. Some patients do not
show serious symptoms, and other patients sometimes show serious symptoms such
as pneumonia and thrombosis. There are a number of factors that increase the
risk of serious illness or death, of which advanced age is the most important
(Loannidis et al. 2020; Banerjee et al. 2020). Patients with a reduced immune
system, in which the blood cells in particular do not function properly, have
an increased risk of a serious course of various viral diseases (Chemaly et al.
2006; Aksoy et al. 2007) and therefore also run a higher risk of any course of
the disease. COVID-19 disease (Parra-Bracamonte et al. 2020; Jee et al. 2020).
To date, a number of treatment options have been proposed for all COVID-19
patients, of which steroid treatment in combination with supportive care
measures remains the cornerstone (WHO living guideline 2020). Treatment with
plasma antibodies has also been studied, but to date none of these therapies
have been successful in reducing the severity of the disease associated with
COVID-19 in hospitalized patients (covid19treatmentguidelines.nih.gov). This is
because 80% of the severe COVID-19 patients included in this study quickly
develop antibodies themselves. It has become clear that this treatment can help
in elderly patients in the first three days after complaints arise. All in all,
these antibodies seem to help early in the course of the disease when
complaints are still mild, but not after this. Whether this antibody treatment
still helps in the prevention of treatment of COVID-19 infections in
immune-compromised patients after admission has not been studied.
Study objective
There have been reports of a more serious course of COVID-19 infections in
patients with a reduced immune system, such as patients with congenital immune
disorders, (haematological) malignancies or patients taking medications that
suppress the immune system. These patients all have to deal with a reduced
immune system, which makes it more difficult for them to make antibodies
against the virus and to clear the virus from the body. Until now, no
treatments have been found with good results for these patients. Treatment with
antibodies from recovered COVID patients may be able to help patients with
reduced immunity to clear up the COVID infection more quickly. As a result, it
is expected that these patients will have to be admitted less long and the
course of the COVID-19 disease will be less severe.
Study design
A phase II, multicenter, cohort specific, randomized controlled, comparative
study.
Intervention
After randomization, one group (43 patients) receives treatment with Nanogam
containing high titre neutralizing anti-SARS-CoV-2 antibodies (further referred
to as Nanogam plus). The other group (43 patients) receives control treatment
with Nanogam without high titre anti SARS-CoV-2 antibodies as control for
Nanogam plus. Treatment is in a double blinded fashion.
Study burden and risks
Infusion of Nanogam plus or control (Nanogam); Viral PCR on day 1, 3, 7, 10, 14
and weekly until discharge, then on months 2, 3, 6, 12. Blood withdrawal weekly
until discharge (mostly covered during standard of care blood withdrawal) and
monthly
Monthly follow-up measurement of anti-SARS-CoV-2 antibodies in serum until 3
months after discharge. Monthly follow-up measurement of SARS-CoV-2 virus by
PCR until 3 months after discharge.
The risks of Nanogam infusion are small and widely known. These consist mainly
of infusion reactions or volume overload.
Benefits of this study may include a shorter disease course and a decrease in
mortality.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Patient is >= 18 years of age, diagnosed with COVID-19 based on a positive PCR
or antigen test in combination with COVID-19 related symptoms (e.g. Fever,
hypoxia, gastrointestinal symptoms).
- Hospitalized.
AND one of immunocompromised conditions/treatments below
B-cell inhibition related ICP
- Use of anti-CD19 or -CD20 directed antibody therapy in 6 months prior to
inclusion.
- Previous or current treatment with drugs that significantly impair B cell
function (e.g. ibrutinib, venetoclax, acalabrutinib, idelalisib etc) within 6
months prior to inclusion
Other immunosuppression/treatment related ICP
- Patients treated with bendamustine, purine analogues or anti-thymocyte
globulin within 6 months prior to inclusion.
- Solid organ transplant patients that are taking systemic immunosuppressive
drugs from at least three pharmacological classes. Or from at least two classes
in combination with negative anti-SARS-CoV-2 antibodies <= 96 hours prior to
inclusion.
Cellular therapy related ICP
- Allogeneic hematopoietic stem cell transplant (HSCT) in 12 months prior to
inclusion.
- HSCT for which systemic therapy against graft-versus-host-disease is used.
- Recipient of CAR-T cells < 2 years prior to inclusion.
Disease related ICP
- Chronic B-cell leukemia*s: CLL, HCL, PLL, multiple myeloma, Waldenströms
macroglobulinemia
Congenital ICP
- Congenital disorder resulting in severe B-cell dysfunction or depletion
requiring immunoglobulin suppletion (e.g. agammaglobulinemia).
Exclusion criteria
- Patient or legal representative is unable to provide written informed consent
- Life expectancy of < 28 days in the opinion of the treating physician
- Has previously participated in this study.
- Has previously received convalescent plasma with high level neutralizing
anti-SARS-CoV-2 antibodies (either in other study or in compassionate use
program).
- Known IgA deficiency (defined as absence of IgA and possibility of anti-IgA
antibodies), patients with disease related reduced levels of IgA (e.g. in
myeloma or lymphoma) may be included in the study.
- Known previous grade 3 or 4 hypersensitivity reactions to treatment with
immunoglobulins
- Patient who has reached endpoint already at admission (direct adjunctive
oxygen therapy in the form of high-flow nasal oxygen (HFNO), mechanical
ventilation or ICU admission for other reason).
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 | EUCTR2020-006075-15-NL |
| CCMO | NL76365.018.21 |