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

SARS-CoV-2 Clinical Trial

Official title:

Phase I/II, Open-Label Dose-Finding Trial of High-Dose mRNA-1273 Booster for Lung Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05280158
• Other study ID #: 22-000192
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 10, 2022
• Est. completion date: February 27, 2023

Study information

• Verified date: January 2024
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: February 27, 2023
• Est. primary completion date: February 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Immunosuppression
• Lung Transplant Recipient
• SARS-CoV-2

Intervention

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.

Locations

Country	Name	City	State
United States	UCLA Clinical Translational Research Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	ModernaTX, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (30)

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;

Adler Y, Charron P, Imazio M, Badano L, Baron-Esquivias G, Bogaert J, Brucato A, Gueret P, Klingel K, Lionis C, Maisch B, Mayosi B, Pavie A, Ristic AD, Sabate Tenas M, Seferovic P, Swedberg K, Tomkowski W; ESC Scientific Document Group. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015 Nov 7;36(42):2921-2964. doi: 10.1093/eurheartj/ehv318. Epub 2015 Aug 29. No abstract available. — View Citation

Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol. 1987 Jun;18(6):619-24. doi: 10.1016/s0046-8177(87)80363-5. No abstract available. — View Citation

Aversa M, Benvenuto L, Anderson M, Shah L, Robbins H, Pereira M, Scheffert J, Carroll M, Hum J, Nolan M, Reilly G, Lemaitre P, Stanifer BP, D'Ovidio F, Sonett J, Arcasoy S; From the Columbia University Lung Transplant Program. COVID-19 in lung transplant recipients: A single center case series from New York City. Am J Transplant. 2020 Nov;20(11):3072-3080. doi: 10.1111/ajt.16241. Epub 2020 Sep 5. — View Citation

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 Feb 4;384(5):403-416. doi: 10.1056/NEJMoa2035389. Epub 2020 Dec 30. — View Citation

Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, Hernan MA, Lipsitch M, Kohane I, Netzer D, Reis BY, Balicer RD. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N Engl J Med. 2021 Sep 16;385(12):1078-1090. doi: 10.1056/NEJMoa2110475. Epub 2021 Aug 25. — View Citation

Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, Garonzik-Wang JM. Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients. JAMA. 2021 Jun 1;325(21):2204-2206. doi: 10.1001/jama.2021.7489. — View Citation

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. — View Citation

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. — View Citation

Damluji AA, Christenson RH, deFilippi C. Clinical Application of Serologic Testing for Coronavirus Disease 2019 in Contemporary Cardiovascular Practice. J Am Heart Assoc. 2021 Feb;10(5):e019506. doi: 10.1161/JAHA.120.019506. Epub 2021 Feb 23. — View Citation

El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, Campbell TB, Clark J, Jackson LA, Fichtenbaum CJ, Zervos M, Rankin B, Eder F, Feldman G, Kennelly C, Han-Conrad L, Levin M, Neuzil KM, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Polakowski L, Mascola JR, Ledgerwood JE, Graham BS, August A, Clouting H, Deng W, Han S, Leav B, Manzo D, Pajon R, Schodel F, Tomassini JE, Zhou H, Miller J; COVE Study Group. Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase. N Engl J Med. 2021 Nov 4;385(19):1774-1785. doi: 10.1056/NEJMoa2113017. Epub 2021 Sep 22. — View Citation

Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018 Dec 18;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072. — View Citation

Gargano JW, Wallace M, Hadler SC, Langley G, Su JR, Oster ME, Broder KR, Gee J, Weintraub E, Shimabukuro T, Scobie HM, Moulia D, Markowitz LE, Wharton M, McNally VV, Romero JR, Talbot HK, Lee GM, Daley MF, Oliver SE. Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee on Immunization Practices - United States, June 2021. MMWR Morb Mortal Wkly Rep. 2021 Jul 9;70(27):977-982. doi: 10.15585/mmwr.mm7027e2. — View Citation

Hall VG, Ferreira VH, Ierullo M, Ku T, Marinelli T, Majchrzak-Kita B, Yousuf A, Kulasingam V, Humar A, Kumar D. Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients. Am J Transplant. 2021 Dec;21(12):3980-3989. doi: 10.1111/ajt.16766. Epub 2021 Aug 4. — View Citation

Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, Selzner N, Schiff J, McDonald M, Tomlinson G, Kulasingam V, Kumar D, Humar A. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. N Engl J Med. 2021 Sep 23;385(13):1244-1246. doi: 10.1056/NEJMc2111462. Epub 2021 Aug 11. No abstract available. — View Citation

Havlin J, Svorcova M, Dvorackova E, Lastovicka J, Lischke R, Kalina T, Hubacek P. Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients. J Heart Lung Transplant. 2021 Aug;40(8):754-758. doi: 10.1016/j.healun.2021.05.004. Epub 2021 May 21. — View Citation

Kamar N, Abravanel F, Marion O, Couat C, Izopet J, Del Bello A. Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients. N Engl J Med. 2021 Aug 12;385(7):661-662. doi: 10.1056/NEJMc2108861. Epub 2021 Jun 23. No abstract available. — View Citation

Kamp JC, Hinrichs JB, Fuge J, Ewen R, Gottlieb J. COVID-19 in lung transplant recipients-Risk prediction and outcomes. PLoS One. 2021 Oct 6;16(10):e0257807. doi: 10.1371/journal.pone.0257807. eCollection 2021. — View Citation

Larson KF, Ammirati E, Adler ED, Cooper LT Jr, Hong KN, Saponara G, Couri D, Cereda A, Procopio A, Cavalotti C, Oliva F, Sanna T, Ciconte VA, Onyango G, Holmes DR, Borgeson DD. Myocarditis After BNT162b2 and mRNA-1273 Vaccination. Circulation. 2021 Aug 10;144(6):506-508. doi: 10.1161/CIRCULATIONAHA.121.055913. Epub 2021 Jun 16. — View Citation

Marion O, Del Bello A, Abravanel F, Couat C, Faguer S, Esposito L, Hebral AL, Izopet J, Kamar N. Safety and Immunogenicity of Anti-SARS-CoV-2 Messenger RNA Vaccines in Recipients of Solid Organ Transplants. Ann Intern Med. 2021 Sep;174(9):1336-1338. doi: 10.7326/M21-1341. Epub 2021 May 25. No abstract available. — View Citation

Messika J, Eloy P, Roux A, Hirschi S, Nieves A, Le Pavec J, Senechal A, Saint Raymond C, Carlier N, Demant X, Le Borgne A, Tissot A, Debray MP, Beaumont L, Renaud-Picard B, Reynaud-Gaubert M, Mornex JF, Falque L, Boussaud V, Jougon J, Mussot S, Mal H; French Group of Lung Transplantation. COVID-19 in Lung Transplant Recipients. Transplantation. 2021 Jan 1;105(1):177-186. doi: 10.1097/TP.0000000000003508. — View Citation

Oliver SE, Wallace M, See I, Mbaeyi S, Godfrey M, Hadler SC, Jatlaoui TC, Twentyman E, Hughes MM, Rao AK, Fiore A, Su JR, Broder KR, Shimabukuro T, Lale A, Shay DK, Markowitz LE, Wharton M, Bell BP, Brooks O, McNally V, Lee GM, Talbot HK, Daley MF. Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine: Updated Interim Recommendations from the Advisory Committee on Immunization Practices - United States, December 2021. MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(3):90-95. doi: 10.15585/mmwr.mm7103a4. — View Citation

Oster ME, Shay DK, Su JR, Gee J, Creech CB, Broder KR, Edwards K, Soslow JH, Dendy JM, Schlaudecker E, Lang SM, Barnett ED, Ruberg FL, Smith MJ, Campbell MJ, Lopes RD, Sperling LS, Baumblatt JA, Thompson DL, Marquez PL, Strid P, Woo J, Pugsley R, Reagan-Steiner S, DeStefano F, Shimabukuro TT. Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021. JAMA. 2022 Jan 25;327(4):331-340. doi: 10.1001/jama.2021.24110. — View Citation

Patone M, Mei XW, Handunnetthi L, Dixon S, Zaccardi F, Shankar-Hari M, Watkinson P, Khunti K, Harnden A, Coupland CAC, Channon KM, Mills NL, Sheikh A, Hippisley-Cox J. Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection. Nat Med. 2022 Feb;28(2):410-422. doi: 10.1038/s41591-021-01630-0. Epub 2021 Dec 14. — View Citation

Rosenblum HG, Hadler SC, Moulia D, Shimabukuro TT, Su JR, Tepper NK, Ess KC, Woo EJ, Mba-Jonas A, Alimchandani M, Nair N, Klein NP, Hanson KE, Markowitz LE, Wharton M, McNally VV, Romero JR, Talbot HK, Lee GM, Daley MF, Mbaeyi SA, Oliver SE. Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices - United States, July 2021. MMWR Morb Mortal Wkly Rep. 2021 Aug 13;70(32):1094-1099. doi: 10.15585/mmwr.mm7032e4. — View Citation

Saez-Gimenez B, Berastegui C, Barrecheguren M, Revilla-Lopez E, Los Arcos I, Alonso R, Aguilar M, Mora VM, Otero I, Reig JP, Quezada CA, Perez V, Valle M, Laporta R, Deu M, Sacanell J, Bravo C, Gavalda J, Lopez-Meseguer M, Monforte V. COVID-19 in lung transplant recipients: A multicenter study. Am J Transplant. 2021 May;21(5):1816-1824. doi: 10.1111/ajt.16364. Epub 2020 Nov 7. — View Citation

Schramm R, Costard-Jackle A, Rivinius R, Fischer B, Muller B, Boeken U, Haneya A, Provaznik Z, Knabbe C, Gummert J. Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients. Clin Res Cardiol. 2021 Aug;110(8):1142-1149. doi: 10.1007/s00392-021-01880-5. Epub 2021 Jul 9. — View Citation

Shostak Y, Shafran N, Heching M, Rosengarten D, Shtraichman O, Shitenberg D, Amor SM, Yahav D, Ben Zvi H, Pertzov B, Kramer MR. Early humoral response among lung transplant recipients vaccinated with BNT162b2 vaccine. Lancet Respir Med. 2021 Jun;9(6):e52-e53. doi: 10.1016/S2213-2600(21)00184-3. Epub 2021 May 5. No abstract available. — View Citation

Simone A, Herald J, Chen A, Gulati N, Shen AY, Lewin B, Lee MS. Acute Myocarditis Following COVID-19 mRNA Vaccination in Adults Aged 18 Years or Older. JAMA Intern Med. 2021 Dec 1;181(12):1668-1670. doi: 10.1001/jamainternmed.2021.5511. — View Citation

Werbel WA, Boyarsky BJ, Ou MT, Massie AB, Tobian AAR, Garonzik-Wang JM, Segev DL. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series. Ann Intern Med. 2021 Sep;174(9):1330-1332. doi: 10.7326/L21-0282. Epub 2021 Jun 15. No abstract available. — View Citation

* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Humoral immunogenicity measured by anti-RBD and anti-spike (S-2P) IgG levels at Day 30.		Day 30 after study drug administration
Secondary	Humoral immunogenicity measured by neutralizing antibody titers from a pseudovirus neutralization assay at Day 30.		Day 30 after study drug administration
Secondary	Cellular immunogenicity measured by cellular response assays including flow cytometry with intracellular staining at Day 30.		Day 30 after study drug administration