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Phase I/II, Open-label Dose-Escalation Randomized Study of High-Dose mRNA-1273 Booster for Lung Transplant Recipients

Sponsor
University of California, Los Angeles (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05280158
Collaborator
ModernaTX, Inc. (Industry)
60
Enrollment
3
Arms
36
Anticipated Duration (Months)

Study Details

Study Description

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 doses of the COVID-19 vaccine.

Condition or Disease Intervention/Treatment Phase
  • Drug: mRNA-1273 (Moderna COVID-19 vaccine)
 Phase 1/Phase 2

Detailed Description

Lung transplant recipients have poor outcomes after COVID-19 infection with case fatality rates ranging between 14-39%. In contrast to immunocompetent participants in vaccine trials, solid organ transplant recipients have had poor responses to SARS-CoV-2 vaccines with several studies reporting anti-SARS-CoV-2 antibody detection in only 34-54% after the second dose. Lung transplant recipients generally require higher levels of immunosuppression due to the allograft's exposure to the external environment and active immune surveillance. Thus, vaccine responses have been even weaker for lung transplant recipients with several studies reporting antibody responses in less than 20% after the second dose. Booster vaccines (3rd dose) appear to improve immune responses for solid organ recipients, but has not been studied specifically for lung transplant recipients.

We propose a single center, Phase I/II open-label dose-escalation trial among lung transplant recipients who previously received all three of their mRNA-1273 vaccine doses after lung transplantation to: standard-dose (50 ug), mid-dose (100 ug) or high-dose (200 ug) booster vaccine. The 3 dose cohorts will be enrolled sequentially as follows: 1) Standard-dose (50 ug) - enroll entire cohort of 20 participants, 2) Mid-dose (100 ug) - enroll sentinel group of 2 participants, assess reactogenicity for 7 days, then enroll remaining cohort of 18 participants if no halting rules are met (Section 12.1), 3) High-dose (200 ug) - enroll sentinel group of 2 participants, assess reactogenicity for 7 days, then enroll remaining cohort of 18 participants if no halting rules are met. Enrollment of the high-dose sentinel group will begin once the mid-dose sentinel group completes their 7-day post-dose assessment without meeting any halting rules. On the study days where more than one cohort is enrolling, participants will be randomly selected into a dose-cohort. In-person visits will occur on Days 1 (booster vaccine), 7 and 30. Telephone visits will occur on Days 3, 90 and 180. Adverse events and reactogenicity will be assessed in person (Days 1, 7 and 30) and by telephone calls (Days 3, 90 and 180). All follow-up visits will include a detailed review for SAEs and AESIs.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
This is a Phase I/II open-label dose-escalation trial among lung transplant recipients who previously received all three of their mRNA-1273 vaccine doses after lung transplantation to: standard-dose (50 ug), mid-dose (100 ug) or high-dose (200 ug) booster vaccine. The 3 dose cohorts will be enrolled and randomized as follows: Standard-dose - enroll entire cohort of 20 participants Mid-dose - enroll sentinel group of 2 participants, assess reactogenicity for 7 days, then enroll remaining cohort of 18 participants if no halting rules are met (Section 12.1) High-dose - enroll sentinel group of 2 participants, assess reactogenicity for 7 days, then enroll remaining cohort of 18 participants if no halting rules are met. Enrollment of the high-dose sentinel group will begin once the mid-dose sentinel group completes their 7-day post-dose assessment without meeting any halting rules.This is a Phase I/II open-label dose-escalation trial among lung transplant recipients who previously received all three of their mRNA-1273 vaccine doses after lung transplantation to: standard-dose (50 ug), mid-dose (100 ug) or high-dose (200 ug) booster vaccine.The 3 dose cohorts will be enrolled and randomized as follows:Standard-dose - enroll entire cohort of 20 participants Mid-dose - enroll sentinel group of 2 participants, assess reactogenicity for 7 days, then enroll remaining cohort of 18 participants if no halting rules are met (Section 12.1) High-dose - enroll sentinel group of 2 participants, assess reactogenicity for 7 days, then enroll remaining cohort of 18 participants if no halting rules are met. Enrollment of the high-dose sentinel group will begin once the mid-dose sentinel group completes their 7-day post-dose assessment without meeting any halting rules.
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Phase I/II, Open-label Dose-Escalation Randomized Study of High-Dose mRNA-1273 Booster for Lung Transplant Recipients
Anticipated Study Start Date :
Mar 10, 2022
Anticipated Primary Completion Date :
Mar 10, 2025
Anticipated Study Completion Date :
Mar 10, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Standard-dose

mRNA-1273 (Moderna COVID-19 vaccine) 50 ug

Drug: mRNA-1273 (Moderna COVID-19 vaccine)
Study Drug will be administered via intramuscular injection (IM). Only one dose of study drug will be administered for the study.
Experimental: Mid-Dose

mRNA-1273 (Moderna COVID-19 vaccine) 100 ug

Drug: mRNA-1273 (Moderna COVID-19 vaccine)
Study Drug will be administered via intramuscular injection (IM). Only one dose of study drug will be administered for the study.
Experimental: High-Dose

mRNA-1273 (Moderna COVID-19 vaccine) 200 ug

Drug: mRNA-1273 (Moderna COVID-19 vaccine)
Study Drug will be administered via intramuscular injection (IM). Only one dose of study drug will be administered for the study.

Outcome Measures

Primary Outcome Measures

  1. Frequency and grade of each solicited local and systemic reactogenicity AE will be recorded on a daily diary using the FDA Toxicity Grading Scale and collected from Day 1 until Day 7. [Day 1 - Day 7 after study drug administration]

  2. Frequency and grade of each unsolicited adverse events (AEs) will be recorded on a daily diary and collected from Day 1 until Day 30. [Day 1 - Day 30 after study drug administration]

  3. Frequency of any serious adverse experiences (SAEs) and adverse events of special interests (AESIs) will be collected from Day 1 until Day 180. [Day 1 - Day 180 after study drug administration]

Secondary Outcome Measures

  1. Humoral immunogenicity measured by anti-RBD and anti-spike (S-2P) IgG levels at Day 30. [Day 30 after study drug administration]

  2. Humoral immunogenicity measured by neutralizing antibody titers from a pseudovirus neutralization assay at Day 30. [Day 30 after study drug administration]

  3. Cellular immunogenicity measured by cellular response assays including flow cytometry with intracellular staining at Day 30. [Day 30 after study drug administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. All adult lung transplant recipients (age≥18) who received all of their COVID-19 vaccines after lung transplantation..

  2. Received three doses of the Moderna mRNA-1273 vaccine at least 3 months prior to study enrollment.

  3. Currently receiving standard regimen of three drug immunosuppression with prednisone, tacrolimus and mycophenolate (minimum 500 mg bid) or myfortic (minimum 360 mg bid).

  4. Agrees not to receive other investigational agents for prophylaxis against COVID-19 including Evusheld monoclonal antibodies for at least 30 days after the study vaccine.

  5. Understands and agrees to comply with the study procedures and provides written informed consent.

  6. Is in stable health without any new or worsening medical conditions in the opinion of the Investigator.

  7. Body mass index (BMI) of 16 kg/m2 to 36 kg/m2 (inclusive) at the Visit1 Day 1 (Booster day).

  8. Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:

  9. Has a negative pregnancy test at Visit 1 Day 1.

  10. Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1).

  11. Has agreed to continue adequate contraception or practice abstinence through 3 months following the booster injection (Day 90).

  12. Is not currently breastfeeding.

  13. Adequate female contraception is defined as consistent and correct use of a Food and Drug Administration (FDA) approved contraceptive method in accordance with the product label. For example:

  1. Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction with spermicide ii. Intrauterine device iii. Prescription hormonal contraceptive taken or administered via oral (pill), transdermal (patch), subdermal, or IM route iv. Sterilization of a female participant's monogamous male partner prior to entry into the study v. Note: periodic abstinence (e.g., calendar, ovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria:
Inclusion Criteria:

  1. All adult lung transplant recipients (age≥18) who received all of their COVID-19 vaccines after lung transplantation..

  2. Received three doses of the Moderna mRNA-1273 vaccine at least 3 months prior to study enrollment.

  3. Currently receiving standard regimen of three drug immunosuppression with prednisone, tacrolimus and mycophenolate (minimum 500 mg bid) or myfortic (minimum 360 mg bid).

  4. Agrees not to receive other investigational agents for prophylaxis against COVID-19 including Evusheld monoclonal antibodies for at least 30 days after the study vaccine.

  5. Understands and agrees to comply with the study procedures and provides written informed consent.

  6. Is in stable health without any new or worsening medical conditions in the opinion of the Investigator.

  7. Body mass index (BMI) of 16 kg/m2 to 36 kg/m2 (inclusive) at the Visit1 Day 1 (Booster day).

  8. Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:

  9. Has a negative pregnancy test at Visit 1 Day 1.

  10. Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1).

  11. Has agreed to continue adequate contraception or practice abstinence through 3 months following the booster injection (Day 90).

  12. Is not currently breastfeeding.

  13. Adequate female contraception is defined as consistent and correct use of a Food and Drug Administration (FDA) approved contraceptive method in accordance with the product label. For example:

  1. Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction with spermicide ii. Intrauterine device iii. Prescription hormonal contraceptive taken or administered via oral (pill), transdermal (patch), subdermal, or IM route iv. Sterilization of a female participant's monogamous male partner prior to entry into the study v. Note: periodic abstinence (e.g., calendar, ovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria:

  1. Previous documented COVID-19 infection.

  2. Use of investigational agents for prophylaxis against COVID-19 within 180 days of the start of the study, including Evusheld monoclonal antibodies.

  3. Prior administration of any non-Moderna SARS-CoV-2 vaccine.

  4. Ongoing therapy for acute cellular or antibody mediated rejection.

  5. Intravenous immunoglobulins (IVIG) administration within the prior 3 months or ongoing IVIG therapy.

  6. Augmented immunosuppression from their baseline regimen.

  7. Anaphylaxis or allergic reaction to any prior vaccines.

  8. 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.

  9. Recent known exposure to someone with SARS-CoV-2 infection or COVID-19 in the prior 2 weeks

  10. Pregnant or breastfeeding.

  11. 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.

  12. Current use of any inhaled substance (eg, tobacco or cannabis smoke, nicotine vapors).

  13. History of illegal substance use or alcohol abuse within the past 2 years. This exclusion does not apply to historical cannabis use that was formerly illegal in the participant's state but is legal at the time of Screening.

  14. Known history of hypertension (HTN) with systolic blood pressure (BP) > 170 mm Hg at the Day 1 visit.

  15. Known history of hypotension with systolic blood pressure < 85 mm Hg at the Day 1 visit.

  16. History of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine.

  17. Bleeding disorder considered a contraindication to IM injection or phlebotomy.

  18. Diagnosis of malignancy within previous 4 years (excluding non-melanoma skin cancer).

  19. Has donated ≥ 450 mL of blood products within 28 days prior to the Day 1 visit or plans to donate blood products during the study.

  20. Received a major surgery including lung transplantation in the past 3 months.

  21. Recent changes to the immunosuppression regimen (prednisone, mycophenolate) over the past 2 months. Changes to tacrolimus dosing is not an exclusion criteria (acceptable).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • University of California, Los Angeles
  • ModernaTX, Inc.

Investigators

  • Principal Investigator: Michael Shino, MD, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Michael Y. Shino, MD, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT05280158
Other Study ID Numbers:
  • 22-000192
First Posted:
Mar 15, 2022
Last Update Posted:
Mar 15, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Michael Y. Shino, MD, Principal Investigator, University of California, Los Angeles
SARS-CoV-2
lung transplant recipient
immunosuppression

Study Results

No Results Posted as of Mar 15, 2022