A Phase I Study on the Safety and Immune-modulatory Effect of Intratumoral (i.t.) Administration of mRNA (Messenger RNA) Encoding Dendritic Cell Activating Proteins in Patients With Early, Resectable Breast Cancer

Patients with early breast cancer and accessible tumor lesions (1.00 to 10 ml volume) that are eligible to either surgical removal of their tumor or neoadjuvant chemotherapy will be injected with the IMP. Patients will be either treated with placebo (buffer alone, 12 patients) or with TriMix mRNA at three dose levels [8 at dose level I (1mg/ml), 8 at dose level II (3mg/ml), and 8 at dose level III (6mg/ml). The volume injected in this group will be adjusted to the tumour volume to ensure a perfusion of around 33% of the tumour volume (33% +/- 5%). Therefore, depending on the patients' tumour size, 500, 1000 or 2000 µl of TriMix mRNA solution or placebo solution will be injected into each tumor. Each patient will receive three administrations of TriMix prior to start of general treatment (surgery or neoadjuvant chemotherapy) separated by one week (7 days +/- 2 days) interval. The last administration will be performed 2 days preoperatively or start of neoadjuvant chemotherapy.
The tumor and peripheral blood samples will be analyzed for immunological changes. If it is decided by the multidisciplinary team that neoadjuvant therapy is more appropriate for the patient, a second tumor biopsy (instead of surgical resection) will be taken 2 days after third administration of TriMix mRNA to assess immunological changes within the tumor. Similarly, patients that refuses to undergo surgery or to receive neoadjuvant chemotherapy can be enrolled into the trial, if they accept three administrations of TriMix followed by a second tumor biopsy.
The study will start with recruitment of the placebo group. The enrollment of the first three patients in each cohort with Trimix mRNA will be staggered with at least one day between the first dose of each individual patient. One week after the third patient of a cohort received the third TriMix mRNA administration, an overall evaluation of the safety and tolerability of this cohort will be done by the principal investigator. The results will be reviewed by an in-house dose evaluation committee overseeing the safety and tolerability of TriMix mRNA.

Start Date12 Nov 2018

Sponsor / Collaborator

Universitair Ziekenhuis Brussel

[+1]

NCT02888756 / TerminatedPhase 2IIT

A Phase IIa Randomized, Placebo Controlled, Double Blinded Study to Evaluate the Safety and Immunogenicity of iHIVARNA-01 in Chronically HIV-infected Patients Under Stable Combined Antiretroviral Therapy

iHIVARNA-01 is a novel therapeutic vaccine for the treatment of HIV-1-infected patients based on in vivo modification of DCs. It consists of HIVACAT-TriMix: mRNA encoding a mixture of APC activation molecules (CD40L, a constitutively active variant of TLR4 and CD70) and the HIV target antigens contained in HIVACAT to be administered through the intranodal route. iHIVARNA-01 aims to achieve the 'functional cure' of HIV infection, i.e. controlling viral replication in the absence of anti-retroviral therapy.

Start Date04 Apr 2017

Sponsor / Collaborator

Vrije Universiteit Brussel

[+10]

100 Clinical Results associated with Trimix(eTheRNA Immunotherapies)

100 Translational Medicine associated with Trimix(eTheRNA Immunotherapies)

100 Patents (Medical) associated with Trimix(eTheRNA Immunotherapies)

Literatures (Medical) associated with Trimix(eTheRNA Immunotherapies)

28 May 2024·The Journal of Sexual Medicine

Delineating patient errors in an intracavernosal injection program

Article

Author: Ortega, Yanira ; Mulhall, John P ; Furtado, Thiago P ; Teloken, Patrick E ; Narus, Joseph ; Wolchasty, Natalie P

AbstractBackgroundIntracavernosal injection therapy (ICI) is a well-established therapeutic strategy for men with erectile dysfunction. Complications are often related to patient error when performong ICI.AimThe objective of this study was to examine patient errors in an established patient training program for performing ICI and identify factors that could predict major errors.MethodsPatients enrolled in our ICI program are trained on technical aspects, and dose titration is begun. Patients are given explicit instructions during training, both verbally and in written form. Records were reviewed for men using ICI for ≥6 months. Multivariable analysis was used to define predictors of major errors.OutcomesErrors were listed as minor (zero-response injection, penile bruising, expired medication) and major (errors potentially leading to priapism: dose self-titration, double injecting).ResultsOverall, 1368 patients met the inclusion criteria and were included in the analysis. The mean patient age was 66 ± 22 (range 29-91) years. Regarding education, 41% of patients had graduate-level education, 48% had college education, and 11% high school education. Mean follow-up was 3.2 ± 7.6 (range 0.5-12) years. The agents used were trimix (62%), bimix (35%), papaverine (2%), and prostaglandin E1 monotherapy (1%). At least 1 error occurred during self-administration in 42% of patients during their time in the program. Errors included zero response to medication due to technical error (8% of patients), penile bruising (34%), use of an expired bottle (18%), self-titration (5%), and double injecting (4% of patients); 12% of men committed ≥1 error during their time in the program. On multivariable analysis, independent predictors of the occurrence of a major error included: young age, graduate-level education, and <12 months of injection use.Clinical implicationsTo the best of our knowledge, this is the first reported study to investigate ICI errors and risk factors. The identification of factors predictive of major errors allows for more tailored and intensive training in this subset of patients.Strengths and limitationsStrengths of this study include a large patient population (1386 men) with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions, enhances the accuracy and reliability of the results. Despite the strengths of the study, recall bias may be a limitation concern.ConclusionThe majority of patients were error free, and the majority of the errors were minor in nature. Major errors occurred in <10% of patients. Younger age, graduate-level education, and less experience with ICI were independent predictors of major errors.

22 Dec 2023·The Journal of Sexual Medicine

Erectile response profiles of men using PDE5 inhibitors combined with intracavernosal injections as part of a penile rehabilitation program after radical prostatectomy

Article

Author: Deveci, Serkan ; Nelson, Christian ; Miranda, Eduardo P ; Mulhall, John P ; Jenkins, Lawrence ; Furtado, Thiago P ; Narus, Joseph

AbstractBackgroundPhosphodiesterase type 5 (PDE5) inhibitor labeling states that these agents should not be used in conjunction with other erectogenic medications for fear of priapism occurring.AimWe explored the risk of priapism and prolonged erections in men in our post–radical prostatectomy (RP) penile injection program who were using regular PDE5 inhibitor and intracavernosal injections (ICIs) as part of their rehabilitation program.MethodsThe study cohort included men on penile injection therapy who (1) were taking tadalafil 5 mg daily or taking sildenafil 25 mg on noninjection days, (2) had an RP, (3) were using their respective PDE5 inhibitor regularly at the time of penile injection training, and (4) complied with the program instructions regarding penile injection use. Demographics, comorbidity details, PDE5 inhibitor dose and utilization, and injection dose and utilization data were collected. All patients underwent in-office injection training and used trimix (papaverine/phentolamine/prostaglandin E1) as the intracavernosal medication.OutcomesPriapism was defined as a patient self-reported penetration hardness erection ≥4 hours in duration, while prolonged erection was defined as a penetration hardness erection lasting ≥2 hours.ResultsA total of 112 tadalafil users and 364 sildenafil users were compared. Mean age and duration post-RP were 62 ± 14 years and 5.2 ± 12 months, respectively, and there was no difference between tadalafil and sildenafil groups. The mean trimix dose was tadalafil 24 ± 24 units and sildenafil 31 ± 37 units (P < .05). Priapism occurred in 2 (1.7%) of 112 tadalafil users and 5 (1.4%) of 364 sildenafil users (P = .47). Excluding those men experiencing priapism on any occasion, those with any reported penetration hardness erection lasting ≥2 hours were 7 (6.3%) of 112 tadalafil users and 12 (3.3%) of 364 sildenafil users (P < .01). A total of 53% of these prolonged erections occurred within the first 6 injections at home (no difference between tadalafil and sildenafil groups).Clinical ImplicationsWe emphasize the need for continued monitoring and education on proper injection techniques to minimize the risk of adverse events in ICI and PDE5 inhibitor combination therapy.Strengths & LimitationsThis study has a relatively large patient population with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions for priapism and prolonged erections, enhances the accuracy and reliability of the results. However, there are some limitations, such as social desirability, confounding factors, and recall bias.ConclusionThere is no significant difference in the incidence of priapism in an ICI program in which men combine ICI with tadalafil or sildenafil. However, tadalafil patients had a higher rate of prolonged erections, which was found to occur mostly early during the titration phase.

01 Dec 2023·Current Urology

A novel technique for unilateral dissection of the penile neurovascular bundle to prevent loss of penile sensation during treatment of Peyronie’s disease—Initial results of a pilot study

Article

Author: Yakubov, Rachel ; Kravchick, Sergey ; Beamer, Matthew ; Pinkhasov, Esther ; Shulman, Daniel ; Pinkhasov, Alexandr M

AbstractBackgroundPlaque incision/excision and grafting are surgical techniques used to treat patients with Peyronie's disease who are refractory to less invasive interventions, have severe penile curvature, or have an hourglass deformity. However, the procedure carries the risk of penile sensory loss because of the need for dissection of the neurovascular bundle (NVB). The aim of this study was to assess the feasibility of a novel technique for unilateral NVB dissection and its ability to preserve penile sensitivity while maintaining adequate correction of the penile curvature.Materials and methodsCharts of patients who underwent unilateral NVB dissection during Peyronie's plaque incision/excision and grafting were retrospectively reviewed. All patients received preprocedural intracavernosal injections of TriMix, and the curvature was measured to be >70 degrees. In 3 cases, an incision and minimal excision of the plaque were performed at the point of maximum curvature on the concave side of the curvature. In 3 cases, Tutoplast allografts (Coloplast US, Minneapolis, MN) were used, whereas autografts were used in 2 other cases. All patients were examined at 1, 3, and 6 months after the procedure when curvature and penile sensation were assessed.ResultsFive patients underwent this procedure. The mean age of patients was 55 years (45–70 years). All plaques were dorsally located. The mean preoperative curvature was 78 degrees (75–90 degrees). At the 6-month follow-up, all patients had <15 degrees residual curvature and were satisfied with their cosmetic results. Only 1 patient continued with phosphodiesterase-5 inhibitors to improve potency at the 6-month follow-up. All patients reported normal penile glans sensation. Four patients experienced decreased sensation at the site of NVB dissection, but this was only detected when compared with the contralateral side. Only 2 patients reported a difference after 6 months, and only a minor area of involvement was noted.ConclusionsUnilateral NVB dissection is a feasible technique that does not compromise surgical success in curvature correction and helps avoid sensory injury to the penile glans.

100 Deals associated with Trimix(eTheRNA Immunotherapies)

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Indication	Highest Phase	Country/Location	Organization	Date
Early Stage Breast Carcinoma	Phase 1	BE	eTheRNA immunotherapies NV	12 Nov 2018
Early Stage Breast Carcinoma	Phase 1	BE	Universitair Ziekenhuis Brussel	12 Nov 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02888756 (iHIVARNA-01, CTgov)	Phase 2	HIV Infections	33	TriMix+iHIVARNA-01 (iHIVARNA-01)	axpfbehess(npamlnuach) = awsuelwgfb tdkdfftstb (peacjinfst, wdtifhewwf - qozyvxylmc) View more	-	09 Dec 2019
				TriMix (TriMix)	axpfbehess(npamlnuach) = rzgdhtwrcl tdkdfftstb (peacjinfst, tuarppuiut - gtfgzkurxv) View more

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