Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of mRNA-1944 in Healthy Adults

Study Overview
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Brief Summary
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This is a Phase 1, FIH, single-center, randomized, placebo controlled, dose escalation study to evaluate the safety, tolerability, PK, and PD of mRNA-1944 in healthy adult subjects. Cohorts of mRNA-1944 are planned to be investigated in a sequential dose escalation manner.

Official Title
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A Phase 1, Randomized, Placebo-Controlled, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of mRNA-1944, Encoding for an Anti-Chikungunya Virus Monoclonal Antibody, in Healthy Adults

Conditions
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Prevention of Chikungunya Virus Infection

Intervention / Treatment
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* Biological: mRNA-1944
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 and ≤ 50 years of age Weight of 50 to 100 kg, inclusive In good general health as determined by medical history, clinical laboratory assessments, ECG results, vital sign measurements, and physical examination findings at screening Has access to consistent and reliable means of contact and agrees to stay in contact with the study site for the duration of the study Exclusion Criteria: Any acute or chronic clinically significant disease, as determined by physical examination or laboratory screening tests Elevated liver function tests or safety laboratory test results Positive screening test for the presence of anti-CHIKV IgG Administration of another investigational study involving any investigational product within 60 days or 5 half-lives, whichever is longer Has received any live attenuated or inactive vaccines within 4 weeks prior to check-in, or plans to receive any vaccine during the study Known or suspected immune-mediated disease or immunosuppressive condition (including lymphoproliferative disorders) Any neurologic disorder History of idiopathic urticaria Any bleeding disorder that is considered a contraindication to study drug infusion or blood collection Receipt of immunoglobulins, a monoclonal antibody or any blood products within the preceding 6 months Any acute illness at the time of enrollment A positive test result for drugs of abuse A positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus type 1 or 2 antibodies A history of active cancer (malignancy) in the last 3 years Donation of ≥ 450 mL blood or blood products within 30 days of study drug infusion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1944<br>Escalating dose levels | Biological: mRNA-1944<br>* mRNA encoding Chikungunya antibody<br>|
| Placebo Comparator: Placebo<br>Saline | Other: Placebo<br>* Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESI) and laboratory abnormalities |  | Through 13 months of study participation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration versus time curve (AUC) |  | Baseline through 28 days post dose | 
| Maximum observed serum concentration (Cmax) after administration of mRNA-1944 |  | Baseline through 28 days post dose | 
| Time of Cmax (tmax) |  | Baseline through 28 days post dose | 
| Terminal elimination half-life (t1/2) |  | Baseline through 28 days post dose | 
| Maximum observed effect (Emax) for chikungunya virus IgG |  | Baseline through 13 months | 
| Time to maximum observed effect for (TEmax) for chikungunya virus IgG |  | Baseline through 13 months | 
| Area under the effect curve (AUEC) for chikungunya virus IgG |  | Baseline through 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chikungunya fever, Alphavirus infections, Togavirus, Viral diseases