Sex: F
Vaccine: COVID19
Symptoms: Angioedema, Body temperature
Clinical narrative: ANGIOEDEMA [LIPS]; This 29-year-old female subject was participating in A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older (mRNA-1273-P301) and experienced angioedema [lips].  The subject's medical history, as provided by the investigator, included angioedema. Concomitant medications reported included drospirenone/ethinyl estradiol and paracetamol. The subject reported a previous history of receiving Restylane dermal filler (crosslinked hyaluronic acid) injections in her lips on 03 May 2019.  The subject was allocated to receive intramuscular mRNA-1273 or placebo for SARS-CoV-2 vaccination. The subject received the first dose of blinded study drug on 25 Aug 2020. The subject's last dose of study drug prior to event onset was on 22 Sep 2020.  On 23 Sep 2020, the subject experienced angioedema [lips]. The subject developed reactogenicity symptoms of fever ten hours after her second dose of study drug, with maximum temperature of 103.1 degrees Fahrenheit, accompanied by chills (grade 2), headache and fatigue (grade 3) and nausea (grade 1). Treatment for lip angioedema included oral diphenhydramine and famotidine.  On 24 Sep 2020, the subject woke with severe lip angioedema without hives, rash, tongue or mouth swelling, dysphagia, dyspnea, wheeze, or stridor. She also complained of painful muscles in the back of her neck and mental fogginess. All symptoms resolved within 48 hours. She had experienced similar lip angioedema following a flu vaccine, approximately one year ago, and had no known allergies or family history of angioedema.   Action taken with study drug in response to the event was not applicable, as the subject had already received both scheduled doses.  The event, angioedema [lips], was considered resolved on 25 Sep 2020.  The investigator assessed the event, angioedema [lips], as related to study drug and not related to study procedure.  Follow-up received on 08 Dec 2020 included updated cosmetic filler details.  Analysis of Similar Events: On 02 Dec 2020, the safety database was searched for events similar to Angioedema [lips] using the following search criteria: Swelling face and Angioedema.  As of 02 Dec 2020 under 019745 for mRNA-1273, two safety reports of similar adverse events have been previously submitted.  MOD-2020-000515:  An unexpected event of facial swelling occurred in a female subject with Juvederm dermal filler cosmetic injection in her cheeks, given on 02 Oct 2020. The event occurred 1 month 6 days after the first dose of blinded study vaccine administration and 2 days after the last dose administration. Contributing factors may include subjects Botox/Filler combination.  MOD-2020-000656: An unexpected event of cheek swelling, bilateral occurred in a female subject who received bilateral Juvederm Voluma (crosslinked hyaluronic acid) cheek injections, approximately 6 months prior to experiencing an unexpected event of cheek swelling, bilateral. The event occurred 1 month after the first dose of blinded study vaccine administration and 1 day after the last dose administration.   There were four cases that were not submitted as Safety Reports (unexpected and unrelated), and were not clinically similar, summarized below:  MOD-2020-000350: An event of laryngeal edema was reported in a subject with medical history of sulfa allergy (hives). The event occurred 4 days after the second dose of blinded study medication administration. The event of laryngeal edema was likely associated with lisinopril therapy which was discontinued due to adverse event.  MOD-2020-000315: An event of angioedema was reported in a subject taking concomitant lisinopril for hypertension. The event occurred 21 days after the first dose of the study medication. The event resolved 2 days later. The event was likely associated with lisinopril therapy, known to cause angioedema, which was discontinued following the adverse event.  MOD-2020-000323: An event of swelling face was reported in a subject with a recent dental history of root canal. One-sided facial swelling, localized to the jaw, occurred 7 days after blinded study vaccine administration and 14 days after root canal. A consultant ENT suggested the event may be due to an odontogenic infection.   MOD-2020-000442: An event of bilateral ankle edema (and concurrent shortness of breath) was reported in a subject with medical history of breast cancer, diabetes mellitus type 2 and hypertension. The event bilateral ankle edema occurred 11 days after the second dose of study drug.   Assessment of Relationship Based on review of available data, the Sponsor cannot rule out a possible cause and effect relationship between administration of blinded study vaccine and the occurrence of lip angioedema. There have been two previously reported, similar events with localized swelling in areas injected with crosslinked hyaluronic acid cosmetic dermal fillers after study drug administration (MOD-2020-000515 and MOD-2020-000656); however, these events involved localized swelling without a diagnosis of angioedema. Events will continue to be monitored for potential product interaction.  After review of the clinical details and investigator comments pertaining to this adverse event, and based upon experience to date, the Sponsor does not believe that changes to the conduct of this clinical trial are warranted. The Company will continue to monitor these, and other, serious adverse events reported in association and will communicate any relevant changes to the protocol, Informed Consent Form, Investigator's Brochure, and/or Core Safety Information.; Reporter's Comments: Company Comment: This case concerns a 29-year-old, white, female subject with a medical history of post-vaccination angioedema of the lips and dermal filler injections in her lips, who experienced an unexpected event of lip angioedema. The event occurred 30 days after the first dose of blinded study vaccine administration and 2 days after the last dose administration. The subject received Restylane dermal filler (hyaluronic acid) injections in her lips about 1 year 5 months before the event onset. The event was considered related to the study vaccine in agreement with the Investigator's assessment.