A Phase 1 interventional study of etoricoxib and H56:IC31 in Tuberculosis, sponsored by Anne Margarita Dyrhol Riise. Completed at 2 sites in Norway. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2022-04-08.
Sponsored by Anne Margarita Dyrhol Riise · Phase 1, Interventional, and Treatment
Tuberculosis (TB) is a global challenge and for the increasing epidemic of multi-drug resistant (MDR)-TB there is restricted treatment options. This calls for research of new immune-modulating treatment strategies that can strengthen the patients immune system to better fight the TB bacteria. The pro-inflammatory, but still immunosuppressive mediator prostaglandin E2 (PGE2) is produced by cyclooxygenase-2 (COX-2) in inflamed infected tissue. Studies from both human and animal models show that COX-2 inhibitors (COX-2i) can improve the immune system and strengthen vaccines responses.
Hypothesis
Approach to test the hypothesis
The hypothesis is that treating TB patients with a therapeutic TB vaccine and COX-2 inhibiting drugs in addition to standard antibiotic TB therapy will improve the patients immune system and boost TB vaccine responses.
The project will provide safety and immunogenicity data from a Norwegian phase 1 clinical trial of the therapeutic TB vaccine candidate H56:IC31 and the COX-2i etoricoxib given to TB patients together with standard TB antibiotics.
The investigators will also perform exploratory in-depth studies of immune regulatory mechanisms and try to identify biomarkers for efficacy of treatment both in humans and in a parallel mouse model. These results may further optimize the therapeutic strategy and prepare for larger clinical trials and finally contribute to new treatment options for MDR-TB.
Objectives:
1,417 studies on the registry are indexed under Tuberculosis; 208 are open to participants now.
This study's enrollment of 39 is below the median of 150 across 952 interventional studies indexed under Tuberculosis.
Browse Tuberculosis studies →This is the only study on the registry with Anne Margarita Dyrhol Riise as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Subjects may receive H56:IC31 vaccination (arm#2 and #4) if they meet the following criteria:
Exclusion Criteria:
Main exclusion criteria:
(i) Study-specific: Disseminated TB. Evidence of a new acute illness that may compromise the safety of the subject in the trial on study day 0. History of autoimmune disease or immunosuppression. History or laboratory evidence of any possible immunodeficiency state. Anemia (\<9 g/100 ml). HIV sero-positivity. Chronic hepatitis B (HBs antigen positive) with increased liver transaminases (ASAT, ALAT) or chronic hepatitis C (HCV RNA positive). Concomitant or sporadic use of NSAID or corticosteroids (>2 times per week). Other immune modulating therapies including DMARDS. Total cholesterol > 7 mmol/L. Hypertension >140/90 mm Hg (treated or untreated) or treated with >1 antihypertensive drug at any blood pressure. Cardiovascular events or stroke in parents, siblings or off-springs occurring \< 55 years of age. Serum creatinine above reference levels (females > 90 µmol/L; males > 105 µmol/L). Known diabetes mellitus type I or diabetes mellitus type II with HbA1c >7%. Pregnancy (S-hCG >5 IU/l for females at childbearing age). Breastfeeding.
arm#1 (n=10) receiving etoricoxib from inclusion day 0 and in 140 days. Step-wise inclusion starting with arm#1,arm#2 and arm#3 (first group) randomized (2:2:1) and if safety data are satisfactory proceeding with arm #4 and the rest of arm#3 randomized (2:2:1).
Drug: etoricoxib
arm#2 (n=10) receiving H56:IC31 vaccine at day 84 and 140 and no etoricoxib.
Biological: H56:IC31
arm#3 (n=10), the first group (n=5) serving as control to arm#1 and arm#2, the next group (n=5) serving as control to arm#4.
arm#4 (n=10) receiving etoricoxib from inclusion day 0 and in 140 days and H56:IC31 vaccine at day 84 and 140.
Drug: etoricoxib · Biological: H56:IC31
cyclooxygenase-2 inhibitor. Anti-inflammatory
Also known as: Arcoxia®
Therapeutic and prophylactic TB vaccine
Safety of etoricoxib (arm#1) assessed by the number of participants with adverse events
Number and % of study patients with AE or SAE
Time frame: From day 0 until day 238 (14 weeks after the last dose of etoricoxib)
Safety of H56:IC31 vaccine (arm#2) assessed by the number of participants with adverse events
Number and % of study patients with AE or SAE
Time frame: From day 0 until day 238. For vaccine related adverse events; immunisation (day 84 and day 140) and 14 days post-immunisation (day 98 and day 154).
Safety of combined etoricoxib and H56:IC31 vaccine (arm#4) assessed by the number of participants with adverse events
Number and % of study patients with AE or SAE
Time frame: From day 0 until day 238 (14 weeks after the last dose of etoricoxib). For vaccine related adverse events; from immunisation (day 84 and day 140) and 14 days post-immunisation (day 98 and day 154).
Immunogenicity of etoricoxib (arm#1)
Total CD4+ T cell cytokine (IFN-γ, IL-2, TNF-α) responses to sum TB peptides.
Time frame: Day 0 (baseline) to day 84
Immunogenicity of H56:IC31 vaccine (arm#2)
Total CD4+ T cell cytokine (IFN-γ, IL-2, TNF-α) responses to sum TB peptides.
Time frame: From before first immunisation (day 84) to 14 days after second immunisation (day 154).
Immunogenicity of combined etoricoxib and H56:IC31 vaccine (arm#4)
Total CD4+ T cell cytokine (IFN-γ, IL-2, TNF-α) responses to sum TB peptides.
Time frame: From before first immunisation (day 84) to 14 days after second immunisation (day 154).
Exploratory immune studies
Study in depth the effect of etoricoxib on immune activation, regulation and TB vaccine immunogenicity measured by the percentage of innate cells (monocytes/MDSC) and CD4+ and CD8+ T cells expressing various activation, supression and regulation markers in response to stimulation with TB antigenic peptide pools (Ag85B, ESAT-6, Rv2660c). Serologi to H56 and gene signature analyses.
Time frame: From day 0 (baseline) until day 238 (study end); 14, 28, 56, 84, 98, 140, 154, 182, 210, 238 days from baseline (selected timepoints for various analysis).
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — The study is published. https://doi.org/10.1038/s41467-021-27029-6
Supporting information: Study protocol, Sap, Analytic code
This study is completed, as verified in Apr 2022. You cannot join it, but the record below documents what was studied.
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