We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05280158
Recruitment Status : Active, not recruiting
First Posted : March 15, 2022
Last Update Posted : December 16, 2022
Sponsor:
Collaborator:
ModernaTX, Inc.
Information provided by (Responsible Party):
Michael Y. Shino, MD, University of California, Los Angeles

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Lung Transplant Recipient SARS-CoV-2 Immunosuppression Drug: mRNA-1273 (Moderna COVID-19 vaccine) Phase 1 Phase 2

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.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Groups will be enrolled as follows:

  1. Mid-dose - Sentinel group, n=2
  2. Standard-dose - Initial group, n=2

  3. Cohort 1: 2:1 Randomization into

    • Mid-dose group, n=18
    • Standard-dose group, n=9
  4. High-dose - Sentinel group, n=2

  5. Cohort 2: 2:1 Randomization into

    • High-dose group, n=18
    • Standard-dose group, n=9

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.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase I/II, Open-Label Dose-Finding Trial of High-Dose mRNA-1273 Booster for Lung Transplant Recipients
Actual Study Start Date : March 10, 2022
Estimated Primary Completion Date : March 10, 2025
Estimated Study Completion Date : March 10, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Day 30 after study drug administration ]
  2. Humoral immunogenicity measured by neutralizing antibody titers from a pseudovirus neutralization assay at Day 30. [ Time Frame: Day 30 after study drug administration ]
  3. Cellular immunogenicity measured by cellular response assays including flow cytometry with intracellular staining at Day 30. [ Time Frame: Day 30 after study drug administration ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  1. All adult lung transplant recipients (age ≥ 18 at the time of consent) who received all of their COVID-19 vaccines after lung transplantation.
  2. Received three or four doses of either the Moderna mRNA-1273 or Pfizer BNT162b2 vaccine with the last dose received at least 4 months prior to study enrollment.
  3. Currently receiving standard regimen of three drug immunosuppression with prednisone, tacrolimus and mycophenolate mofetil (cellcept, minimum 250 mg bid) or mycophenolate sodium (myfortic, minimum 180 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. Female participants of childbearing potential (<1 year since start of menopause) may be enrolled in the study if the participant fulfills all the following criteria:

    1. Has a negative pregnancy test at Visit 1 Day 1.
    2. 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).
    3. Has agreed to continue adequate contraception or practice abstinence through 3 months following the booster injection (Day 90).
    4. Is not currently breastfeeding.
    5. 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:

    i. 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 90 days of the start of the study, including Evusheld monoclonal antibodies.
  3. Ongoing therapy for acute cellular or antibody mediated rejection.
  4. Intravenous immunoglobulins (IVIG) administration within the prior 3 months or ongoing IVIG therapy.
  5. Anaphylaxis or allergic reaction to any prior vaccines.
  6. History of anaphylaxis or other significant adverse reaction requiring medical intervention after receipt of a vaccine.
  7. 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.
  8. Pregnant or breastfeeding.
  9. 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.
  10. Known history of hypertension (HTN) with systolic blood pressure (BP) > 180 mm Hg at the Day 1 visit.
  11. Known history of hypotension with systolic blood pressure < 85 mm Hg at the Day 1 visit.
  12. Bleeding disorder considered a contraindication to IM injection or phlebotomy.
  13. Active malignancy diagnosed within previous 4 years (excluding non-melanoma skin cancer).
  14. Received a major surgery including lung transplantation in the past 3 months.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05280158


Locations
Layout table for location information
United States, California
UCLA Clinical Translational Research Center
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
ModernaTX, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Yusaku Michael Shino, MD University of California, Los Angeles
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:
Corbett KS, Flynn B, Foulds KE, Francica JR, Boyoglu-Barnum S, Werner AP, Flach B, O'Connell S, Bock KW, Minai M, Nagata BM, Andersen H, Martinez DR, Noe AT, Douek N, Donaldson MM, Nji NN, Alvarado GS, Edwards DK, Flebbe DR, Lamb E, Doria-Rose NA, Lin BC, Louder MK, O'Dell S, Schmidt SD, Phung E, Chang LA, Yap C, Todd JM, Pessaint L, Van Ry A, Browne S, Greenhouse J, Putman-Taylor T, Strasbaugh A, Campbell TA, Cook A, Dodson A, Steingrebe K, Shi W, Zhang Y, Abiona OM, Wang L, Pegu A, Yang ES, Leung K, Zhou T, Teng IT, Widge A, Gordon I, Novik L, Gillespie RA, Loomis RJ, Moliva JI, Stewart-Jones G, Himansu S, Kong WP, Nason MC, Morabito KM, Ruckwardt TJ, Ledgerwood JE, Gaudinski MR, Kwong PD, Mascola JR, Carfi A, Lewis MG, Baric RS, McDermott A, Moore IN, Sullivan NJ, Roederer M, Seder RA, Graham BS. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. N Engl J Med. 2020 Oct 15;383(16):1544-1555. doi: 10.1056/NEJMoa2024671. Epub 2020 Jul 28.
Corbett KS, Nason MC, Flach B, Gagne M, O'Connell S, Johnston TS, Shah SN, Edara VV, Floyd K, Lai L, McDanal C, Francica JR, Flynn B, Wu K, Choi A, Koch M, Abiona OM, Werner AP, Moliva JI, Andrew SF, Donaldson MM, Fintzi J, Flebbe DR, Lamb E, Noe AT, Nurmukhambetova ST, Provost SJ, Cook A, Dodson A, Faudree A, Greenhouse J, Kar S, Pessaint L, Porto M, Steingrebe K, Valentin D, Zouantcha S, Bock KW, Minai M, Nagata BM, van de Wetering R, Boyoglu-Barnum S, Leung K, Shi W, Yang ES, Zhang Y, Todd JM, Wang L, Alvarado GS, Andersen H, Foulds KE, Edwards DK, Mascola JR, Moore IN, Lewis MG, Carfi A, Montefiori D, Suthar MS, McDermott A, Roederer M, Sullivan NJ, Douek DC, Graham BS, Seder RA. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Science. 2021 Sep 17;373(6561):eabj0299. doi: 10.1126/science.abj0299. Epub 2021 Sep 17.
Abu S, Roguin A, Hellou E, Ishai A, Shoshan U, Mahamid L. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company ' s public news and information . 2020;

Layout table for additonal information
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: March 15, 2022    Key Record Dates
Last Update Posted: December 16, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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, University of California, Los Angeles:
SARS-CoV-2
lung transplant recipient
immunosuppression