Covid-19 Living Data

Trial NCT05142553
Publication Corominas J, Lancet Reg Health Eur, 2023

Funding: Mixed (Hipra Scientific, S.L.U (HIPRA) ; Centre for the Development of Industrial Technology/Spanish Ministry of Science and Innovation.)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Spain Follow-up duration (months): 3.2
	PHH-1V booster (after 2 doses of BNT162b2 prime) (n = 522) BNT162b2 booster (after 2 doses of BNT162b2 prime)(n = 260)
Inclusion criteria	Aged 18 years or older who had received two doses of the BNT162b2 vaccine at least 182 days and less than 365 days after their second dose Body Mass Index (BMI) between 18 and 40 kg/m2 negative SARS-CoV-2 PCR test at the time of enrolment willingness to avoid all other vaccines within 4 weeks before and after vaccination in this study (seasonal influenza vaccination was allowed if it was received at least 14 days before or after the study booster) willing to refrain from blood donation during the study women of childbearing potential must have a negative blood or urine pregnancy test at Screening and Day 0 (before vaccination). Subjects who are women of childbearing potential must be willing to use highly effective contraceptive methods or have practiced sexual abstinence from the screening visit until 8 weeks after the vaccination (Day 0). Highly effective contraceptive methods include oral, intravaginal, or transdermal combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation intrauterine device intrauterine hormone-releasing system bilateral tubal occlusion vasectomised partner, condom and sexual abstinence Subjects who are men and not sterilised must be willing to avoid impregnating female partners from Screening until 8 weeks after vaccination (Day 0).
Exclusion criteria	Pregnancy or breastfeeding an ongoing serious psychiatric condition history of respiratory disease requiring daily medications history of significant cardiovascular disease history of neurological or neurodevelopmental conditions ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin any confirmed or suspected autoimmune, immunosuppressive or immunodeficiency disease/condition (iatrogenic or congenital) including human immunodeficiency virus infection use of immunosuppressants coagulation or bleeding disorder chronic liver disease history of SARS-CoV-2 infection close contact with anyone positive for SARS-CoV-2 infection within 15 days before screening life expectancy of less than 12 months any medical disease (acute, subacute, intermittent, or chronic) or condition that, in the opinion of the Investigator, compromises the subject’s safety, precludes vaccination, or compromises interpretation of the results an acute illness within 72 hours before Day 0 that, in the opinion of the Investigator, may interfere with the evaluation of safety parameters has received investigational drug within 90 days before Screening or plans to participate in another interventional clinical study (drug/biologic/device) within 12 months after vaccination (Day 0) a history of hypersensitivity or severe allergic reactions, including anaphylaxis, generalised urticarial, angioedema and other significant reactions related to food, drugs, vaccines, or pharmaceutical agents, which are likely to be exacerbated by any component of the COVID-19 vaccine HIPRA (including the oil in water adjuvant equivalent to MF59C.1) has received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days before vaccination (Day 0) Ever been included in a trial with an experimental vaccine against COVID-19.
Interventions
	Intervention 1 IM dose of 40 mcg PHH-1V booster, 182-364 days after 2 prime doses of BNT162b2
	Control 1 IM dose of 30 mcg BNT162b2 booster, 182-364 days after 2 prime doses of BNT162b2
Participants
	Randomized 782 participants
	Characteristics of participants Type of participants: Healthy adults N=782 281 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 19-76
	Description of participants Healthy adults with no history of COVID-19 and who had received two doses of the BNT162b2 in 10 centres in Spain.
Primary outcome
	In the register 1) Changes of the immunogenicity against Wuhan [Time Frame: 14 days]: Neutralisation titre measured as inhibitory concentration 50 (IC50) for each individual sample and geometric mean titre (GMT) for treatment group comparison at Baseline and Day 14. 2) Safety and tolerability of PHH-1V as third dose [Time Frame: 7 days]: Number, percentage, and characteristics of solicited local reactions through Day 7 after vaccination. 3) Safety and tolerability of PHH-1V as third dose [Time Frame: 28 days]: Number, percentage, and characteristics of unsolicited local and systemic adverse events (AEs) through Day 28 after vaccination. 4) Safety and tolerability of PHH-1V as third dose [Time Frame: 364 days]: Number and percentage of serious adverse events (SAEs), adverse event of special interest (AESI) and medically attended adverse events (MAAE) through Day 364. 5) Safety and tolerability of PHH-1V as third dose [Time Frame: Days 14, 28, 182, and 364]: Change from baseline in safety laboratory parameters at Days 14, 28, 182, and 364 after vaccination. 6)Changes of the immunogenicity against Omicron BA.1 [ Time Frame: Day 14 ] Neutralisation titre measured as inhibitory concentration 50 (IC50) by PBNA and reported as log10 concentration for each individual sample and GMT, at Day 14 post-dose 4 of PHH-1V in cohort 2 versus post-dose 3 in cohort 2 (cohort 2 having three doses of Comirnaty + the frouth dose of PHH-1V).
	In the report 1) Humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost 2) Safety and tolerability of PHH-1V as a boost
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes Data accessibility: All data relevant to the study are included in the article or uploaded as supplementary information. Further data are available from the authors upon reasonable request and with permission of HIPRA S.A. Corresponding author Teresa Prat: teresa.prat@hipra.com
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print, the study registry and protocol were used in data extraction and risk of bias assessment. This is an ongoing study reporting a preliminary analysis; study visits were scheduled on day 0, day 14, day 28 and at 3, 6 and 12 months - data up to day 98 are reported herein. The trial (n = 782) achieved the target sample size reported in the supplementary methods (n = 602), although recruitment is still listed as ongoing in the recently updated registry. The target sample size (N=1000) specified in the registry was not achieved, possibly because the registry mentions two parts to the trial. There is no change from the trial registration in the intervention and control treatments. This study was updated on January 23rd, 2023 after a new version of the preprint became available. This trial was updated on February 27th, 2023 with data extracted from the forth version of the preprint. This trial was updated on March 21th, 2023 with data extracted from the fifth version of the preprint. This trial was updated on May 15th, 2023 after publication of the study report.