High-Dose Moderna mRNA-1273 Booster Study for Lung Transplant Recipients

Phase 1

Terminated

Conditions: Immunosuppression
Lung Transplant Recipient
SARS-CoV-2

Interventions: Drug: mRNA-1273 (Moderna COVID-19 vaccine)

Registration Number: NCT05280158

Lead Sponsor: University of California, Los Angeles

Brief Summary: Lung transplant recipients have poor outcomes after COVID-19 infection with mortality. Due to the immunosuppression, they have had poor responses to SARS-CoV-2 vaccine and remain at high risk of poor outcomes. This is a Phase I/II clinical trial to evaluate the safety and immune response from a higher dose mRNA-1273 vaccine among lung transplant recipients who have already received three or four doses of the COVID-19 vaccine.

Detailed Description: This is a Phase I/II open-label dose-finding trial among lung transplant recipients who received three or four mRNA vaccine doses (mRNA-1273 or BNT162b2) after lung transplantation to: standard-dose (50 ug), mid-dose (100 ug) or high-dose (200 ug) mRNA-1273 booster vaccine. Sixty participants will be enrolled into three dose groups: 1) Standard-dose - 20 participants, 2) Mid-dose - 20 participants, 3) High-dose - 20 participants. The first 2 participants in both the mid-dose and high dose groups will be considered the 'sentinel' group. Participants in the sentinel group will receive the vaccine and undergo a 7-day observation period for safety and reactogenicity before additional participants are enrolled into that dose group.

Overall study enrollment will begin with the mid-dose sentinel group (n=2). During the observation period for the mid-dose sentinel group, we will enroll two participants into the standard-dose group. Once the mid-dose sentinel group completes their 7-day observation period without triggering halting rules and is approved to proceed by the DSMB, we will enroll the next 27 participants (Cohort 1) with a 2:1 randomization into the mid-dose (n=18) and standard-dose (n=9) groups.

Once all 20 participants have received their mid-dose vaccine without triggering halting rules and is approved to proceed by the DSMB, we will enroll the high-dose sentinel group (n=2). Once the high-dose sentinel group completes their 7-day observation period without triggering halting rules and is approved to proceed by the DSMB, we will enroll the next 27 participants (Cohort 2) with a 2:1 randomization into the high-dose (n=18) and standard-dose (n=9) groups. All 20 participants in the mid-dose group will be enrolled prior to the enrollment of the high-dose group.

We will perform stratified randomization for the two cohorts based on: 1) the number of prior doses, and 2) prior receipt of any BNT162b2 vaccines. Randomization with be done by the UCLA Clinical and Translational Science Institute (CTSI) statistics team based on scheduled participants prior to the study visit. The 6 participants in the sentinel (n=4) and initial (n=2) groups (Table 1) will be assigned into the 3 groups based on their scheduled visit day.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Previous documented COVID-19 infection.
Use of investigational agents for prophylaxis against COVID-19 within 90 days of the start of the study, including Evusheld monoclonal antibodies.
Ongoing therapy for acute cellular or antibody mediated rejection.
Intravenous immunoglobulins (IVIG) administration within the prior 3 months or ongoing IVIG therapy.
Anaphylaxis or allergic reaction to any prior vaccines.
History of anaphylaxis or other significant adverse reaction requiring medical intervention after receipt of a vaccine.
Is acutely ill or febrile 24 hours prior to or at the Day 1 visit. Fever is defined as a body temperature ≥ 38.0°C/100.4°F. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
Pregnant or breastfeeding.
Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the investigator's judgment.
Known history of hypertension (HTN) with systolic blood pressure (BP) > 180 mm Hg at the Day 1 visit.
Known history of hypotension with systolic blood pressure < 85 mm Hg at the Day 1 visit.
Bleeding disorder considered a contraindication to IM injection or phlebotomy.
Active malignancy diagnosed within previous 4 years (excluding non-melanoma skin cancer).
Received a major surgery including lung transplantation in the past 3 months.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard-dose	mRNA-1273 (Moderna COVID-19 vaccine)	mRNA-1273 (Moderna COVID-19 vaccine) 50 ug
Mid-Dose	mRNA-1273 (Moderna COVID-19 vaccine)	mRNA-1273 (Moderna COVID-19 vaccine) 100 ug
High-Dose	mRNA-1273 (Moderna COVID-19 vaccine)	mRNA-1273 (Moderna COVID-19 vaccine) 200 ug

Primary Outcome Measures

Name	Time	Method
Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR)	Day 1 - Day 7 after study drug administration	Solicited local and systemic reactogenicity adverse events were documented daily in a dedicated diary, and assigned a grade 1-3 according to the "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" (FDA grading scale). Higher grades are assigned to more severe events.
Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary	Day 1 - Day 30 after study drug administration	Comprehensive recording of occurrence and severity grade of unsolicited adverse events (AEs) daily. These events were documented in a dedicated diary starting from Day 1 of the study and continued through to Day 30. Data collection encompassed adverse events not specifically solicited, with each event's frequency recorded for analysis.
Participants Reporting Any Serious Adverse Experiences (SAEs) and Adverse Events of Special Interests (AESIs) Related to the Intervention From Day 1 Until Day 180.	Day 1 - Day 180 after study drug administration	This comprehensive data collection is intended to provide insights into the occurrence of significant adverse events and specific adverse events of interest over an extended period

Secondary Outcome Measures

Name	Time	Method
Humoral Immunogenicity Measured by Anti-RBD and Anti-spike (S-2P) IgG Levels at Day 30.	Day 30 after study drug administration	This evaluation provides insights into the vaccine's ability to induce an immune response by quantifying specific antibody levels targeting key viral components, contributing to the understanding of vaccine efficacy and immune response dynamics.
Humoral Immunogenicity Measured by Neutralizing Antibody Titers From a Pseudovirus Neutralization Assay at Day 30.	Day 1, Day 30 after study drug administration	Provide a direct measure of the vaccine-induced immune response's ability to neutralize viral infection, offering critical insights into vaccine efficacy and immune response effectiveness
Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining.	Day 1, Day 30 after study drug administration	Percent of total CD8+ T Cells to quantify vaccine-induced cellular immune response, the activation and functionality of specific immune cell populations to contribute to understanding the vaccine's ability to elicit a robust cellular immune response, which is essential for effective protection against viral infections.
Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining.	Day 1, Day 30 after study drug administration	Percent of total CD4+ T Cells to quantify vaccine-induced cellular immune response, the activation and functionality of specific immune cell populations to contribute to understanding the vaccine's ability to elicit a robust cellular immune response, which is essential for effective protection against viral infections.