E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal failure stage 4 and 5. |
Njursvikt stadium 4 och 5 |
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E.1.1.1 | Medical condition in easily understood language |
Kidney disease |
Njursjukdom |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
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 |
To investigate the proportion of patients with renal failure stadium 4 and 5, with or without dialysis, who have seroconverted 2 weeks after vaccine dose 2 or have at least 10^2 increase of neutralizing antibodies towards SARS-CoV-2 compared with baseline. |
Att undersöka hur stor andel av patienter med kronisk njursvikt stadium 4 och 5 med eller utan dialys har serokonverterat 2 veckor efter vaccindos 2 eller har minst 10^2 ökning av neutraliserande antikroppar mot SARS-CoV-2 jämfört med baseline.
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E.2.2 | Secondary objectives of the trial |
- What proportion of patients with chronic renal failure stadium 4 or 5, with or without dialysis, have remaining immunity, i.e. continual detection of antibodies towards SARS-CoV-2, 3, 6 and 12 months after the second vaccine dose.
-Difference in immune response before and two weeks after an extra/booster dose, if relevant
- How common are side effects for covid-vaccination and what side effects occurs (AE/SAE/SUSAR) |
- Hur stor andel av patienter med kronisk njursvikt stadium 4 och 5 med eller utan dialys har kvarstående immunitet, dvs fortsatt påvisade antikroppar mot SARS-CoV-2, 3, 6 och 12 månader efter andra vaccindosen.
-Skillnad i immunsvar före och två veckor efter extrados/boosterdos om aktuellt.
- Hur vanligt är det med biverkningar på covid-vaccinen och vilka biverkningar förekommer (AE/SAE/SUSAR) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult 18-65 years old. - Chronic renal failure stadium 4 or 5 with or without dialysis. - The study patient has given her/his consent to participate in the study. |
- Vuxen mellan 18-65 år - Kronisk njursvikt stadium 4 eller 5 med eller utan dialys - Forskningspersonen har gett sitt skriftliga samtycke till att delta i studien.
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E.4 | Principal exclusion criteria |
- Previous renal transplantation - Concomitant medication with immune-modulating agent - Current or previous known covid-19 infection at inclusion (i.e previous PCR positive for SARS-CoV-2 or previous detection of SARS-CoV-s antibodies). Antibodies detected during screening for this study is not an exclusion criterion. - Information in the Health declaration for covid-19 vaccination (17) which suggests that vaccination is inappropriate. - Vaccinated or planned vaccination with other vaccine within the next 14 days that can not be rescheduled. - Pregnancy - Hypersensitivity for any substance in the vaccine - Mental impairment, reluctance to participate or language difficulties which entail difficulties to understand the implication of the study - Individual who is not considered appropriate for study participation due to any other reason. |
• Tidigare njurtransplantation • Samtidig medicinering med immunmodulerande läkemedel • Vid inklusion pågående eller tidigare känd covid-19 sjukdom( dvs tidigare PCR positiv för SARS-CoV-2 eller tidigare påvisade antikroppar mot SARS-CoV-2). Antikroppar som påvisas först i samband med screening för studien är inte ett exklusionskriterium. • Uppgifter i Hälsodeklaration inföor covid-19 vaccination (17) som gör vaccination olämpligt: • Vaccinerad eller planerad vaccination med annat vaccin inom 14 dagar som inte kan flyttas • Graviditet • Överkänslighet mot någon substans i vaccinet • Mental oförmåga, ovilja eller språksvårigheter som medför svårighet att förstå innebörden av att delta i studien • Individ som prövaren av annan anledning inte uppfattar som lämplig att delta.
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E.5 End points |
E.5.1 | Primary end point(s) |
SARS-CoV-2 IgG directed towards the spike protein in blood collected before the vaccination and 2 weeks after the second vaccine dose. The analysis will be performed by ELISA. |
SARS-CoV-2 IgG riktade mot spike proteinet mäts i blod taget före vaccination och 2 veckor efter andra vaccindosen. Analysen görs med ELISA. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before vaccination (screening visit), Visit 2 (dose 2), Visit 3 (+14 days from dose 2) See table 1 in the study protocol. |
Innan vaccinering (screeningbesök), Besök 2 (dos 2), Besök 3 (+ 14 dagar från dos 2). See tabell 1 i studieprotokollet. |
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E.5.2 | Secondary end point(s) |
- SARS-CoV-2 IgG and IgA will be measured in blood collected before the vaccination and at 4 other timepoints during one year after the second vaccine dose, and two weeks after an extra/booster dose if relevant
- Epitope mapping of the antibody response as well as binding strength of the antibody may be evaluated.
- Analysis for cellular immunity will be performed on an ongoing basis throughout the study and after all participants have been included.
- The number of memory B-cells targeted towards the SARS-CoV-2 spike protein will be measured.
- Memory B-cells may be sorted and genetic analysis (e.g. sequensing of the B cell receptor) may be carried out in order to examine how polyclonal and differentiated the humoral immune response is after vaccination.
- The number of T cells targeted towards the SARS-CoV spike protein will be measured with in vitro stimulation with spike and with analysis of intracellular cytokine production. Polarisation of Th1 vs. Th2 response will be measured with the represenation of different cytokine profiles, e.g. IFN gamma vs IL-4.
- Proportion of reported side effects (AE/SAE/SUSAR). |
- SARS-CoV-2 IgG samt IgA mäts i blod taget före vaccination och vid upprepade tillfällen under ett år efter andra vaccindosen, och två veckor efter en extra/booster dos om relevant.
- Epitopmapping av antikroppssvaret samt mätning av bindningsstyrka av antikropparna (som ett kvalitetsmåttt på humorala svarets mognad) kan komma att göras.
- Analyser för cellulär immunitet kommer utföras både fortlöpande under studien och efter att samtliga forskningspersoner inkluderats .
- Antalet minnes B celler mot SARS-CoV-2 spike protein kommer mätas.
- Även minnes B celler kan komma att sorteras och genetiska analyser utföras såsom sekvensering av B cellsreceptorn för att utvärdera hur polyklonalt och differentierat den humorala svarat är efter vaccination.
- Antalet minnes T celler mot SARS-CoV-2 spike protein mäts med stimulering in vitro med peptider av spike och analys av intracellulär cytokinproduktion med hjälp av flödescytometri. Polarisering av Th1 vs Th2 svar mäts med representation av olika cytokinprofiler tex IFN-gamma vs IL4.
- Andel med rapporterade biverkningar (AE/SAE/SUSAR).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For SARS-CoV-2 IgG and IgA measurements: Visit 4 (+ 3 months from dose 2), Visit 5 (+ 6 months from dose 2), Visit 6 (+12 months from dose 2), and two weeks after an extra/booster dose if relevant (Extra visit 2).
Cellular immunity is measured at all study visits except for visit 4 (3 months). |
För SARS-CoV IgG and IgA mätningar: Besök 4 (+ 3 månader från dos 2), Besök 5 (+ 6 månader från dos 2), Besök 6 (+ 12 månader från dos 2), och två veckor efter en extra/booster dos om relevant (Extrabesök 2).
Cellulär immunitet mäts vid samtliga studiebesök förutom vid Besök 4 (3 månader).
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | No |
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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LPLV |
Sista patientens sista besök |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |