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

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

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.

Study Overview

• Status: Completed
• Conditions: Prevention of Chikungunya Virus Infection
• Intervention / Treatment: Other: Placebo; Biological: mRNA-1944

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Phase 1 Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline	Other: Placebo; Saline
Experimental: mRNA-1944; Escalating dose levels	Biological: mRNA-1944; mRNA encoding Chikungunya antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Publications and helpful links

General Publications

• Deng YQ, Zhang NN, Zhang YF, Zhong X, Xu S, Qiu HY, Wang TC, Zhao H, Zhou C, Zu SL, Chen Q, Cao TS, Ye Q, Chi H, Duan XH, Lin DD, Zhang XJ, Xie LZ, Gao YW, Ying B, Qin CF. Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters. Cell Res. 2022 Apr;32(4):375-382. doi: 10.1038/s41422-022-00630-0. Epub 2022 Feb 24.
• August A, Attarwala HZ, Himansu S, Kalidindi S, Lu S, Pajon R, Han S, Lecerf JM, Tomassini JE, Hard M, Ptaszek LM, Crowe JE, Zaks T. A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus. Nat Med. 2021 Dec;27(12):2224-2233. doi: 10.1038/s41591-021-01573-6. Epub 2021 Dec 9. Erratum in: Nat Med. 2022 May;28(5):1095-1096.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2019
• Primary Completion (Actual): June 7, 2021
• Study Completion (Actual): June 7, 2021

Study Registration Dates

• First Submitted: February 1, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Chikungunya fever; Alphavirus infections; Togavirus; Viral diseases
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Alphavirus Infections; Togaviridae Infections; Chikungunya Fever
• Other Study ID Numbers: mRNA-1944-P101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No