This study has been transitioned to CTIS with ID 2024-518686-10-00 check the CTIS register for the current data. To describe and investigate safety and tolerability of the intradermal delivery of two fractional doses of 3/3 µg Comirnaty Original/…
ID
Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
- Musculoskeletal and connective tissue disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Nature, frequency and severity of local reactions. Solicited adverse events
include: pain, redness and swelling at the injection site and pain and swelling
at the regional lymph nodes
Nature, frequency and severity of systemic events. Solicited adverse events
include: flare-up, fever, fatigue, headache, chills, vomiting, diarrhoea, new
or worsened muscle pain, and new or worsened joint pain.
Use of corticosteroids, antipyretics and painkillers
Secondary outcome
• SARS-CoV 2 WT neutralising antibody titres rate on Day 1 and Day 43
• SARS-CoV-2-spike protein-specific binding IgG level on Day 1 and Day 43
• B-cell and T-cell responses on day 1 and day 43
Background summary
Patients with Fibrydysplasia Ossificans Progressiva (FOP) have an increased
risk of fatal SARS-CoV-2 infection due to their restricted pulmonary function
though are unable receive the approved intramuscular vaccination. Intramuscular
vaccination will likely cause a flare-up and subsequent heterotopic
ossification (HO). Current treatment guidelines also recommend to avoid all
intramuscular (IM) vaccinations and advise to immunize through subcutaneous
vaccination when possible. Actual data on vaccine tolerability, safety and
immunogenicity is however limited. Lanchoney et al reported that IM injection
of diphtheria-pertussis-tetanus (DPT) vaccines caused flare-ups and subsequent
HO in 27% of children with FOP. Kou et al. followed up on patients who had
received mRNA COVID-19 vaccination and reported that 1 out of 12 patients
experienced a flare-up and subsequent HO after IM vaccination.
Normally, vaccines are administered into the muscle. However, the skin (dermis)
contains a much higher density of antigen presenting dendritic cells than does
muscle. The skin lymphatic system is extensively organised into several plexus
systems, which aids efficient transport of vaccine antigen and antigen
presenting dendritic cells to the regional lymph nodes. A fractional vaccine
dose introduced directly into the papillary dermis (intradermal administration,
ID) might be as effective as the intramuscular administration of the full
standard dose to achieve a protective immune response. This principle has
already been demonstrated for rabies, yellow fever, inactivated polio and
seasonal influenza vaccine. At the moment, a
research group at the LUMC is performing the IDSCOVA-trial, evaluating the
tolerability, safety and immunogenicity of intradermal mRNA SARS-CoV-2
vaccination compared to standard intramuscular vaccination.
In preclinical studies the intradermal route has been shown to be a very
effective way for mRNA vaccine administration. At the moment, a research group
at the LUMC is performing the IDSCOVA-trial, evaluating the tolerability,
safety and immunogenicity of intradermal mRNA SARS-CoV-2 vaccination compared
to standard intramuscular vaccination in healthy adults. Results in a preprint
show that 20µg ID elicited a sufficient antibody response in all subjects with
significantly less systemic sides effects such as fever, myalgia, joint pains
and headaches. If the intradermal route is also a safe and effective route of
vaccination in patients with FOP, it would prove a preferred alternative to
intramuscular vaccination in patients
with FOP.
At the moment, the omicron variant is the dominant variant in the Netherlands.
Due to policy decisions, the moderna vaccine is not currently available in the
Netherlands. To best accomodate the current corona situation in the
Netherlands, we will vaccinate the patients with the 3/3 µg Comirnaty
Original/Omicron BA.4-5 vaccin intradermally.
Study objective
This study has been transitioned to CTIS with ID 2024-518686-10-00 check the CTIS register for the current data.
To describe and investigate safety and tolerability of the intradermal delivery
of two fractional doses of 3/3 µg Comirnaty Original/Omicron BA.4-5 vaccin in
patients with Fibrodysplasia Ossificans Progressiva. Additionally to measure
the immunogenicity through SARS-CoV 2 neutralising antibody, SARS-CoV-2-spike
protein-specific binding IgG and IgA antibody levels and RBD-specific IgG
antibody levels with be measures in all participants at D0, D29 and D57.
Study design
Prospective interventional cohort study
Intervention
Participants will receive 3/3 µg Comirnaty Original/Omicron BA.4-5 vaccine
followed by a second dose on day 28 through the intradermal route.
Study burden and risks
FOP patients have an increased risk of severe SARS-CoV-2 infection due to
(severe) reduced lung function, but can usually not be vaccinated
intramuscularly because of the risk of heterotopic ossification. Previous
research has shown that intradermal COVID19 vaccination is safe and effective
in healthy volunteers. If this also turns out to be the case in FOP patients,
this vulnerable population can be protected against serious disease. This
justifies the potential risk of more pronounced local side effects from
intradermal injection and venipuncture.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
• Fibrodysplasia ossificans progressiva as determined by confirmation of any
causative genetic mutation in the ACVR1 gene
• 18 years or older
• Participants who are willing and able to comply with all scheduled visits,
vaccination tests and other study procedure
• Capable of giving personal signed consent as described in appendix 1, which
includes compliance with the requirements and restrictions listed in the ICD
and this protocol
Exclusion criteria
• History of severe adverse reaction associated with a vaccine and/or severe
allergic reaction (eg, anaphylaxis) to any component of the study
intervention(s).
• Receipt of medications intended to prevent SARS-CoV-2 infection.
• Current clinical complaints consistent with SARS-CoV-2 infection (three or
more of the following complaints: headache, loss of smell, sore throat,
hoarseness, cough, chest pain, shortness of breath, fatigue, diarrhea, fever).
• SARS-CoV-2 vaccination 6 months prior to participation.
• Immunosuppressed individuals with known or suspected immunodeficiency, as
determined by history.
• Individuals with a history of autoimmune disease or an active autoimmune
disease requiring therapeutic intervention.
• SARS-CoV-2 PCR-positive EMA approved lateral flow test at the screening
before receipt of fist vaccine dose
• Receipt of any other non-study vaccine within 28 days, before first study
dose.
• Anticipated receipt of any other non-study vaccine within 28 days, after last
study dose administration.
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 |
|---|---|
| EU-CTR | CTIS2024-518686-10-00 |
| EudraCT | EUCTR2022-000692-39-NL |
| CCMO | NL83562.018.22 |