Anti-Covid-19 vaccine protection in immunocompromised children (1-15 years) with acute leukemia and their siblings (= 12 years). Phase I-II trial evaluating safety and post-vaccination humoral and cellular immunogenicity / PACIFIC STUDY

Anti-Covid-19 vaccine protection in immunocompromised children (1-15 years) with acute leukemia and their siblings (= 12 years). Phase I-II trial evaluating safety and post-vaccination humoral and cellular immunogenicity / PACIFIC STUDY - PACIFIC

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-002966-41-FR

Enrollment

150

Registered

2021-06-28

Start date

2021-08-13

Completion date

Unknown

Last updated

2021-08-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Interventions

Trade Name: COMIRNATY® Pharmaceutical Form: Concentrate for dispersion for injection INN or Proposed INN: COVID-19 mRNA vaccine (nucleoside-modified) Other descriptive name: COVID-19 mRNA vaccine (nuc

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Children 1-15 years of age: • With acute lymphoblastic leukemia undergoing chemotherapy (minimum 2 weeks after the last PEG-ASPARAGINASE injection) or whose last chemotherapy is less than or equal to 12 months. • With acute myeloid leukemia within 12 months after the end of treatment - Brother or sister between 12 and 15 years of age living in the same household as the child with ALL more than 50% of the time - Informed consent of parents - Patient affiliated to a social security plan Are the trial subjects under 18? yes Number of subjects for this age range: 150 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - Documented SARS-CoV-2 infection in progress or within the last three months - Known clinical allergy to polyethylene glycol (PEG) - Pregnant in the first trimester or breastfeeding - Platelet count < 50 G/L or PNN count < 0.5G/L at time of vaccination - Vaccinated within 4 weeks prior to the first injection or scheduled to receive a licensed vaccine 4 weeks after the last injection. - Any bleeding disorder considered a contraindication to intramuscular injection - History of severe adverse events following vaccine administration including anaphylactic reaction and associated symptoms such as rash, difficulty breathing, angioedema, and abdominal pain, or a history of allergic reaction that may be exacerbated by a vaccine component - Participant who has been vaccinated with BCG within the past year.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the safety and immunogenicity of COMIRNATY® (BNT162b2) vaccine (two injections 21-28 days apart) in children with LA (1-15 years) and their siblings (=12 years);Secondary Objective: - To evaluate the level of anti-S IgG at incl., between D21 and D28, 6 and 12 months after the 1st dose. - Study the level of anti-N IgG at incl., between D21 and D28, 2 , 6 and 12 months of the 1st dose. - Anti-Spike IgG neutralization capacity (if anti-Spike IgG is detected) measured at D0, 2, 6 and 12 months after the 1st inj. - Specific T-cell response (Elispot) to SARS-CoV-2 at D0, 2, 6 and 12 months after the 1st inj. - SARS-CoV-2 PCR positivity in the nasopharynx at D8, D15 and D28 in case of infection - Incidence of symptomatic SARS-CoV-2 infections, AND a positive SARS-CoV-2 PCR, within 12 months of vaccination - Genotype of the SARS-CoV-2 strain in case of infection - Time between planned and actual date of chemotherapy in case of infection - 10-item WHO COVID-19 scale in case of infection - In case of infection in a vaccinated child, PCR SARS-CoV-2 of the entourage as soon as the diagnosis is made and within 7 d. of contact (if the 1st PCR is neg.);Primary end point(s): Primary co-criteria In children under 12 years of age: - Dose-limiting toxicity (DLT) defined on the presence within 7 days after vaccine injection of a vaccine-attributable adverse event of grade 3 or higher (detailed below) - Significant increase in anti-Spike IgG titer AND positive anti-S IgG neutralization test 2 months after the 1st injection 1) Tolerance criteria Dose-limiting toxicity (DLT) is defined according to the criteria listed in Table 1. They are derived from the CTCAE V5.0 (37) and the FDA guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" (38). Any other CTCAE V5.0 grade 3-4 unexpected clinical adverse events related to vaccination. A Critical Event and LDT Review Committee will validate	—

Measure

Time frame

Main Objective: To evaluate the safety and immunogenicity of COMIRNATY® (BNT162b2) vaccine (two injections 21-28 days apart) in children with LA (1-15 years) and their siblings (=12 years);Secondary Objective: - To evaluate the level of anti-S IgG at incl., between D21 and D28, 6 and 12 months after the 1st dose. - Study the level of anti-N IgG at incl., between D21 and D28, 2 , 6 and 12 months of the 1st dose. - Anti-Spike IgG neutralization capacity (if anti-Spike IgG is detected) measured at D0, 2, 6 and 12 months after the 1st inj. - Specific T-cell response (Elispot) to SARS-CoV-2 at D0, 2, 6 and 12 months after the 1st inj. - SARS-CoV-2 PCR positivity in the nasopharynx at D8, D15 and D28 in case of infection - Incidence of symptomatic SARS-CoV-2 infections, AND a positive SARS-CoV-2 PCR, within 12 months of vaccination - Genotype of the SARS-CoV-2 strain in case of infection - Time between planned and actual date of chemotherapy in case of infection - 10-item WHO COVID-19 scale in case of infection - In case of infection in a vaccinated child, PCR SARS-CoV-2 of the entourage as soon as the diagnosis is made and within 7 d. of contact (if the 1st PCR is neg.);Primary end point(s): Primary co-criteria In children under 12 years of age: - Dose-limiting toxicity (DLT) defined on the presence within 7 days after vaccine injection of a vaccine-attributable adverse event of grade 3 or higher (detailed below) - Significant increase in anti-Spike IgG titer AND positive anti-S IgG neutralization test 2 months after the 1st injection 1) Tolerance criteria Dose-limiting toxicity (DLT) is defined according to the criteria listed in Table 1. They are derived from the CTCAE V5.0 (37) and the FDA guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" (38). Any other CTCAE V5.0 grade 3-4 unexpected clinical adverse events related to vaccination. A Critical Event and LDT Review Committee will validate

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Secondary

Measure	Time frame
Secondary end point(s): - To evaluate the level of anti-S IgG at inclusion, between D21 and D28, 6 months and 12 months after the 1st dose. - Study the level of anti-N IgG at inclusion, between D21 and D28, 2 months, 6 months and 12 months of the 1st dose. - Anti-Spike IgG neutralization capacity (if anti-Spike IgG is detected) measured at D0, 2, 6 and 12 months after the 1st injection - Specific T-cell response (Elispot) to SARS-CoV-2 at D0, 2, 6 and 12 months after the first injection - SARS-CoV-2 PCR positivity in the nasopharynx at D8, D15 and D28 in case of infection - Incidence of symptomatic SARS-CoV-2 infections, defined as the presence of at least one of fever, dyspnea, cough, chest pain, anosmia, agueusia, diarrhea, or vomiting, AND a positive SARS-CoV-2 PCR, within 12 months of vaccination - Genotype of the SARS-CoV-2 strain in case of infection - Time between planned and actual date of chemotherapy in case of infection - 10-item WHO COVID-19 scale in case of infection - In case of infection in a vaccinated child, PCR SARS-CoV-2 of the entourage (contact cases) as soon as the diagnosis is made and within 7 days of contact (if the first PCR is negative);Timepoint(s) of evaluation of this end point: At inclusion, between D21 and D28, at 6 months and 12 months of the 1st dose.	—

Measure

Time frame

Secondary end point(s): - To evaluate the level of anti-S IgG at inclusion, between D21 and D28, 6 months and 12 months after the 1st dose. - Study the level of anti-N IgG at inclusion, between D21 and D28, 2 months, 6 months and 12 months of the 1st dose. - Anti-Spike IgG neutralization capacity (if anti-Spike IgG is detected) measured at D0, 2, 6 and 12 months after the 1st injection - Specific T-cell response (Elispot) to SARS-CoV-2 at D0, 2, 6 and 12 months after the first injection - SARS-CoV-2 PCR positivity in the nasopharynx at D8, D15 and D28 in case of infection - Incidence of symptomatic SARS-CoV-2 infections, defined as the presence of at least one of fever, dyspnea, cough, chest pain, anosmia, agueusia, diarrhea, or vomiting, AND a positive SARS-CoV-2 PCR, within 12 months of vaccination - Genotype of the SARS-CoV-2 strain in case of infection - Time between planned and actual date of chemotherapy in case of infection - 10-item WHO COVID-19 scale in case of infection - In case of infection in a vaccinated child, PCR SARS-CoV-2 of the entourage (contact cases) as soon as the diagnosis is made and within 7 days of contact (if the first PCR is negative);Timepoint(s) of evaluation of this end point: At inclusion, between D21 and D28, at 6 months and 12 months of the 1st dose.

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Countries

France

Contacts

Public ContactElodie SOLER

Assistance Publique – Hôpitaux de Paris

elodie.soler@aphp.fr01 44 84 17 35

Outcome results