E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fibrodyplasia Ossificans Progressiva (FOP) |
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E.1.1.1 | Medical condition in easily understood language |
Genetic condition which causes abnormal formation of bone at abnormal locations such as in the muscles, tendons and ligaments. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10068715 |
E.1.2 | Term | Fibrodysplasia ossificans progressiva |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To describe and investigate safety and tolerability of the intradermal delivery of two fractional doses of 20 μg mRNA-1273 in patients with Fibrodysplasia Ossificans Progressiva. |
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E.2.2 | Secondary objectives of the trial |
To compare the immunogenicity of patients with FOP after intradermal delivery of two fractional doses of 20 μg mRNA-1273 with that of two doses of 20 μg mRNA-1273 vaccine through intramuscular delivery and intradermal delivery on Day 43, as previously investigated in LUMC cohort of healthy adults |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria: • Fibrodysplasia ossificans progressiva as determined by confirmation of any causative genetic mutation in the ACVR1 gene as previously described (1). • 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 • Females only: female volunteers of childbearing potential (i.e. have a uterus and are neither surgically sterilised nor post-menopausal) must not be pregnant or breastfeeding. They should agree to use adequate contraception at least up to four weeks following the final dose of mRNA-1273 vaccine.
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study: • 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. • Women who are pregnant or breastfeeding. • Planned pregnancy within four weeks after the final injection. • 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• 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
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |