E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adults with congenital or acquired B cell/antibody deficiency |
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E.1.1.1 | Medical condition in easily understood language |
Adults with congenital or acquired B cell/antibody deficiency |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084465 |
E.1.2 | Term | COVID-19 vaccination |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase I: The primary objective of phase I of this trial is to evaluate the safety and tolerability of CoVac-1 in adults with congenital or acquired B cell/antibody deficiency.
Phase II: The primary objective of phase II of this trial is to evaluate the efficacy of the CoVac-1 vaccine in terms of induction of SARS-CoV-2 specific T cells.
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E.2.2 | Secondary objectives of the trial |
Phase I: The secondary objective of phase I of this trial is to evaluate the efficacy of the CoVac-1 vaccine. In addition, humoral immune responses will be assessed.
Phase II: The secondary objectives of phase II of this trial are to evaluate the safety and tolerability of CoVac-1. In addition, humoral immune responses will be assessed.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult (≥18 years) male or non-pregnant, non-lactating female 2. Primary antibody deficiency syndrome or Secondary antibody deficiency syndrome, defined by one of the following: - IgG < 5.5 g/l - Ongoing substitution of immunoglobline for hypogammaglobinemia - Anti-CD20 antibody (monospecific) therapy for malignant disease: after combined Anti-CD20 antibody therapy with chemotherapy (e.g. fludarabin, cyclophosphamid, bendamustin, anthracycline, vincristin) (within 1-6 months post therapy) ongoing or up to 6 months after single agent Anti-CD20 antibody therapy ongoing or up to 6 months after combined Anti-CD20 antibody therapy with BTKinhibitors or BCL2-inhibitors Anti-CD20 antibody maintenance therapy 3. Ability to understand and voluntarily sign an informed consent form 4. Ability to adhere to the study visit schedule and other protocol requirements 5. Female patients of child bearing potential (FCBP) and male patients with partners of child bearing potential, who are sexually active, must agree to the use of two effective forms (at least one highly effective method) of contraception. This should be started from the signing of the informed consent and continue until three months after vaccination. Furthermore, contraception must be carried on by patients receiving B-cell depleting therapies for the whole duration of the treatment. 6. Postmenopausal or evidence of non-child-bearing status. For women of childbearing potential: negative urine or serum pregnancy test within 7 days prior to study treatment. Postmenopausal or evidence of nonchildbearing status is defined as: - Amenorrhoea for 1 year or more following cessation of exogenous hormonal treatments - Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50 |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating females
2. Participation in any clinical trial with intake of any investigational or non-registered vaccine product
3. Any concomitant disease affecting the effect of the therapeutic vaccine or interfering with the study primary endpoint: - Active infection - Psychiatric disorders - Known systemic anaphylaxis
4. Prior or current infection with SARS-CoV-2 as assessed by medical history, or by throat/nose swab (PCR) or serologically documented immunization against SARS-CoV-2 (after infection or vaccination) 5. persisting symptoms developed after vaccination against SARS-CoV-2 with one of the approved vaccines-products
6. HIV infection, chronic or active hepatitis B or C
7. History of relevant CNS pathology or current relevant CNS pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia/haemorrhage, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder, excluding febrile seizures as child)
8. Baseline laboratory CD4+ T cell count < 100 µl
9. The following pre-existing medical conditions: - Chronic liver failure defined as Child-Pugh Score ≥B - Chronic renal failure defined as GFR <40 ml/min/1,73m2 - Serious pre-existing cardiovascular disease such as NYHA ≥ III - Sickle cell anemia
10. Known hypersensitivity to any of the components included in the CoVac-1 vaccine
11. Pre-existing auto-immune disease except for Hashimoto thyroiditis and mild (not requiring immunosuppressive treatment) psoriasis
12. Patient receiving active treatment with Proteosome- Inhibitors (e.g. Bortezomib), Phosphoinositid-3-Kinase-Inhibors (e.g. Idelalisib) 13. Patient receiving active treatment with small molecules, including Tyrosine Kinases-Inhibitors (e.g. Ibrutinib), Proteosome-Inhibitors (e.g. Bortezomib), Bcl-2-Inhibitors (Venetoclax) or Phosphoinositid-3-Kinase-Inhibors (e.g. Idelalisib) 14. Intention of receiving one dose of an already approved vaccine against SARS-CoV-2 before day 56 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I Based on the primary objective the primary endpoint is defined as: • The nature, frequency, and severity of AEs and/or SAEs associated with CoVAC-1: - Solicited: ADRs/AEs occurring from the time of each injection throughout V4 days following the procedure, facilitated by use of a patient diary - Unsolicited: AEs from the time of injection throughout V5 following injection - SAEs from the time of injection until the final study visit for each subject - Incidence of AESIs until the final study visit for each subject Phase II: Based on the primary objective the primary endpoint is defined as: • Development of a CoVac-1 specific T cell response to at least one of the single SARS-CoV-2 T cell epitopes included in the CoVac-1 vaccine in > 80% of the patients until V4 measured by IFN-γ ELISpot ex vivo and after in vitro T cell amplification (compared to Visit 1)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 98, Month 5 and 8 after peptide vaccination |
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E.5.2 | Secondary end point(s) |
Phase I Cellular immunity: Development of a CoVac-1 specific T cell response to at least one of the single SARS-CoV-2 T cell epitopes included in the CoVac-1 vaccine on Visits 2, 3, 4, 5, 6 measured by IFN-γ ELISpot ex vivo and after in vitro T cell amplification (compared to Visit 1), this includes: Cellular conversion rate (CCR) at Visits 2, 3, 4, 5, 6 after immunization Assessment of humoral immune response: Development of SARS-CoV-2 specific antibodies at Visits 2, 3, 4, 5, 6 after immunization (measured by Siemens sCOVG Assay at the Central Laboratory of the University Hospital Tubingen). Phase II - Solicited: ADRs/AEs occurring from the time of each injection throughout V4 following the procedure, facilitated by use of a patient diary - Unsolicited: AEs from the time of injection throughout V5 following injection - SAEs from the time of injection until the final study visit for each subject - Incidence of AESIs until the final study visit for each subject Assessment of humoral immune response: Development of SARS-CoV-2 specific antibodies at Visits 2, 3, 4, 5, 6 after immunization (measured by Siemens sCOVG Assay at the Central Laboratory of the University Hospital Tubingen). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 98, Month 5 and 8 after peptide vaccination |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of Study for a subject enrolled in this trial is defined as the last study visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |