A phase Ia, dose-finding study to assess the safety and immunogenicity of an Orf virus-based COVID-19 vaccine booster (Prime-2-CoV_Beta) in healthy adults

Phase 1

Suspended

Conditions: The clinical trial itself does not investigate a medical condition or disease. Rather, the safety and immunogenicity of a vaccine against SARS-CoV-2 infection is being investigated.

Interventions: Biological: Prime-2-CoV_Beta

Registration Number: 2024-511266-36-00

Lead Sponsor: Universitaetsklinikum Tuebingen AöR

Brief Summary: This is an open-label, first-in-human, dose-finding study to evaluate the safety and immunogenicity of a booster vaccination of Prime-2-CoV_Beta in healthy participants who had received the full course of vaccination, including booster vaccination (i.e., having received 3 doses) with the Pfizer/BioNTech-BNT162b2 vaccine (Comirnaty).

Detailed Description: Eligible participants will undergo baseline assessments and will receive 1 injection of Prime-2-CoV_Beta at Day 1. Participants will be followed up through 6 months post-booster vaccination. Follow-up visits will be performed at Days 4, 8, 15, 29, and Months 3 and 6, to assess the safety, tolerability, and immunogenicity of Prime-2-CoV_Beta. Additional safety and tolerability data will be assessed 1 day and 2 days after booster vaccination (Days 2 and 3) by telephone. A total of 60 participants is planned to be vaccinated in 5 cohorts of 12 participants each. Dose ranging of Prime-2-CoV_Beta will be done by dose escalation with doses ranging from 3x10000 plaque forming units (PFUs) up to 3x10 000 000 PFUs

Recruitment & Eligibility

Status: Temporarily halted

Sex: Not specified

Target Recruitment: 72

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Prime-2-CoV_Beta	Prime-2-CoV_Beta, dose: 30 000 PFUs
Cohort 2	Prime-2-CoV_Beta	Prime-2-CoV_Beta, dose: 300 000 PFUs
Cohort 3	Prime-2-CoV_Beta	Prime-2-CoV_Beta, dose: 3 000 000 PFUs
Cohort 4	Prime-2-CoV_Beta	Prime-2-CoV_Beta, dose: 150 000 000 PFUs
Cohort 5	Prime-2-CoV_Beta	Prime-2-CoV_Beta, dose: 30 000 000 PFUs

Primary Outcome Measures

Name	Time	Method
Proportion of participants with unsolicited treatment-emergent adverse events throughout the study	Day 1 (vaccination day) to month 6 (end of study visit, ±14 days)	All unsolicited adverse events which occur after the first administration of investigational product are defined as treatment-emergent adverse events. Treatment-emergent adverse events will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events) and presented by system organ class and preferred term, as well as by severity.
Proportion of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) throughout the study	Day 1 (vaccination day) to month 6 (end of study visit, ±14 days)	All safety data will be summarized descriptively overall and by cohort. TEAEs will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events) and presented by system organ class and preferred term, as well as by severity.
Proportion of participants with solicited local adverse events (first 7 days after Prime-2-CoV_Beta booster vaccination): pain at injection site, redness, induration, and swelling.	Day 1 (vaccination day) to day 8 (Visit 3; ±1 day)	Solicited local adverse events will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events).
Proportion of participants with solicited systemic adverse events (first 7 days after Prime-2-CoV_Beta booster vaccination): fever, fatigue, headache, chills, vomiting, nausea, diarrhea, new or worsened muscle pain, new or worsened joint pain.	Day 1 (vaccination day) to day 8 (Visit 3; ±1 day)	Solicited systemic adverse events will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events).

Secondary Outcome Measures

Name	Time	Method
Geometric mean titers (GMT) of receptor-binding protein-specific IgG antibodies	Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days)	Immunogenicity endpoints will be descriptively analyzed by cohort and visit. Separate analyses will be done for the different parameters, e.g., different antibodies evaluated with different serological immunogenicity assays.
Proportion of participants with adverse events of special interest throughout the study	Day 1 (vaccination day) to day 8 (Visit 3; ±1 day)	Adverse events of special interest will be summarized by descriptive statistics using contingency tables (counts of events,number and proportion of participants with events) and presented by system organ class and preferred term, as well as by severity. The frequency (% of participants) of adverse events of special interest throughout the study will be tabulated.
Level of neutralizing antibody titers versus SARS CoV-2 (Wuhan wild type) at each post-booster vaccination assessment	Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days)	Immunogenicity endpoints will be descriptively analyzed by cohort and visit. Separate analyses will be done for the different parameters, e.g., different antibodies evaluated with different serological immunogenicity assays.
Geometric mean fold rise (GMFR) of neutralizing antibodies (versus Wuhan wild type) from Baseline to each post-booster vaccination assessment	Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days)	The fold change from Baseline will be computed for each participant. The fold rise is calculated as the ratio of the post- vs pre-vaccination titer value. The fold change from Baseline will be summarized using descriptive statistics by cohort and visit. Additionally, the GMFR with 95% CI will be presented.
IgG antibody titer versus SARS-CoV-2 receptor-binding protein	Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days)	Immunogenicity endpoints will be descriptively analyzed by cohort and visit. Separate analyses will be done for the different parameters, e.g., different antibodies evaluated with different serological immunogenicity assays.
Geometric mean fold rise of receptor-binding protein-specific IgG antibodies from Baseline	Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days)	The fold change from Baseline will be computed for each participant. The fold rise is calculated as the ratio of the post- vs pre-vaccination titer value. The fold change from Baseline will be summarized using descriptive statistics by cohort and visit. Additionally, the geometric mean fold rise with 95% confidence interval will be presented.

Trial Locations

Locations (2): Bernhard-Nocht-Institut Fuer Tropenmedizin
🇩🇪
Hamburg, Germany
Eberhard Karls Universitaet Tuebingen
🇩🇪
Tuebingen, Germany
Bernhard-Nocht-Institut Fuer Tropenmedizin
🇩🇪Hamburg, Germany
Johanna Fischer-Herr
Site contact
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studien@bnitm.de