Pönitz, Germany

LSTR in Chevron Osteotomy

Evaluation of the Safety and Efficacy of Revita® DMR on Body Weight Maintenance in Subjects with Obesity Who Have Achieved At Least 15% Weight Loss on Tirzepatide

Title A Prospective, Randomized, Double-Blind, Sham-Controlled, Multicenter, Pivotal Study to Assess the Efficacy of Revita® Duodenal Mucosal Resurfacing (DMR) on Body Weight Maintenance in Participants with Obesity Who Have Achieved at Least 15% Weight Loss on GLP-1 Based Pharmacotherapy (REMAIN-1) Short Title Revita® Duodenal Mucosal Resurfacing for Weight Maintenance (REMAIN-1) Protocol Number C-00700 Study Population Male and non-pregnant non-lactating females aged 21 -70 years, who do not have type 1 or type 2 diabetes mellitus, and with a body mass index (BMI) ≥ 30 kg/m2 Trial Design Study C-00700 is a multi-Stage study which may be conducted in parallel. Stage 1 is an open-label training Stage enrolling participants already on GLP-1 based therapy (prior to study enrollment) with at least 15% total body weight loss (TBWL) since initiation of the GLP-1 based drug. Those participants who lost at least 15% total body weight on the GLP-1 based drug and wish to discontinue the use, will be eligible to receive Revita DMR procedure. An open-label training Stage (Stage 1) will require treating endoscopy sites without prior experience with Revita DMR to perform DMR in up to 4 participants per site prior to treating any participant in the randomization Stage (Stage 2) to ensure consistency of study procedures prior to initiating randomization. Sites with prior Revita DMR training and experience may, but are not required to, enroll participants from this stage in parallel to Stage 2. Stage 2 is a randomized, double-blind, sham-controlled trial that will investigate the impact of Revita® Duodenal Mucosal Resurfacing (DMR), compared with a sham endoscopic procedure, on the maintenance of body weight loss in participants with obesity (BMI ≥ 30 kg/m2). Eligible participants will receive an open-label, tirzepatide run-in, dose-escalation period of approximately 16-26 weeks duration. Those participants who lose at least 15% total body weight during the tirzepatide run-in treatment period will subsequently discontinue tirzepatide and be randomized to either Revita DMR or a sham procedure. Randomization at the end of the tirzepatide run-in period for eligible participants will be stratified by sex (male, female) and Baseline BMI (<30 or ≥30 kg/m2). Stage 2 will consist of two independent Stage parts, Stage 2a and Stage 2b, which will enroll sequentially. Both Stages will enroll, randomize, treat, and follow-up participants in the same manner (DMR vs Sham, 2:1, double blind). - Stage 2a will consist of approximately 45 randomized participants with a range of 30-60. An exploratory safety and efficacy analysis will be performed after the last participant in Stage 2a completes the 12-week visit or discontinues the study. - Stage 2b will consist of approximately 315 randomized participants. The final efficacy analysis will be performed after the last participant in Stage 2b completes the 52-week visit or discontinues the study. Phase Pivotal Sites/Facilities Multicenter trial with up to 35 Revita treatment centers with experience in advanced endoscopy procedures in the United States Study Intervention and Sham The Revita® System is an endoscopic treatment consisting of a single catheter and console designed to lift the duodenal mucosa with saline followed by controlled circumferential hydrothermal ablation of the mucosa. The sham procedure consists of placing the Revita® Catheter into the duodenum for a minimum of 30 minutes with no manipulation of the device or activation of the catheter. Number of Participants Approximately 865 participants will be screened for the entire study. Stage 1 (Open-label). Approximately 175 participants will be screened, and up to 100 participants will be treated with Revita DMR. Stage 2 (Randomized). For Stage 2a, approximately 90 participants will be screened, and approximately 60 participants will be enrolled into the tirzepatide run-in treatment period to successfully randomize approximately 45 participants with a range of 30-60 to DMR or sham in a 2:1 ratio. For Stage 2b, approximately 600 participants will be screened, and approximately 400 participants will be enrolled into the tirzepatide run-in treatment period to successfully randomize approximately 315 participants in a 2:1 DMR (n=210) or sham (n=105) treatment ratio. An upper limit of 75% enrollment of females will be used to ensure a sufficiently large sample of men. No more than 20% of total number of randomized subjects will be treated at any single site. Study Duration The total estimated time from open enrollment until completion of data analyses is 128 weeks. Participant Study Duration Stage 1 (Open-Label) The total participant study duration is approximately 54 weeks in Stage 1 of the study with the following study periods: - A screening period up to 1 week - A run-in period: - Participants enter the study having already achieved at least a 15% body weight loss on a GLP-1 based drug. After meeting all eligibility criteria in visit 1, participants will go directly to study visit 7, the baseline visit. Visit 7 (baseline visit): Eligible participants will advance from study visit 1 (screening) immediately to study visit 7 at which time their GLP-1 based drug will be discontinued. Visit 8 (study intervention): Participants will have study intervention (visit 8) one week after GLP-based drug discontinuation. For these participants, total participant study duration is approximately 54 weeks. • Study intervention and follow up: The study intervention and post-study intervention period (52 weeks)-An endoscopic evaluation will first be performed to confirm participant eligibility. Immediately following confirmation of participant eligibility, qualifying participants will receive the DMR intervention. The endoscopy evaluation and study intervention will take place during the same endoscopy session. Post- intervention follow up will occur until 52 weeks after intervention. Stage 2 (Randomized) The total participant study duration is approximately 68-78 weeks with the following study periods: - A screening period up to 1 week - A tirzepatide run-in dose-escalation period (approximately 16-26 weeks) during which time (and until) participants successfully achieve at least 15% body weight loss. - Visit 2-6 (tirzepatide run-in): Tirzepatide will be initiated at the end of visit 2, and dose escalation will occur, as tolerated, during study visits 2-6 up to a maximum tolerated dose as per the tirzepatide FDA approved prescribing information or investigator discretion. - Visit 7 (baseline visit): Once at least 15% weight loss is achieved at any of these visits 2-6, participants will immediately advance to study visit 7 as his/her next scheduled study visit. During the interval between the documented ≥ 15% weight loss and study visit 7, participants will continue to abide by the recommended tirzepatide dose-escalation regimen per protocol. At study visit 7, tirzepatide will be discontinued. - Visit 8 (study intervention): Participants will have visit 8 one week after tirzepatide discontinuation. The study intervention and post-study intervention period (52 weeks): An endoscopic evaluation will first be performed to confirm participant eligibility. Immediately following confirmation of participant eligibility, participants will be randomized to receive either the DMR or sham intervention. The endoscopy evaluation and study intervention will take place during the same endoscopy session. Post-study intervention follow up will occur in a blinded manner until 52 weeks after intervention.

CPRIT: Patient Adherence to Lung Cancer Screening

Primary Objectives/Aims 1. Determine rates of lung cancer scheduling and screening at the UTMB and UT Tyler LCS programs. 2. Using state-of-the-art machine learning (ML) approaches, develop prediction models for adherence to screening guidelines for newly eligible and established patients. Investigators will leverage data from BRFSS, UT Tyler and UTMB to develop and validate the prediction model, ensuring its generalizability and accuracy. 3. Survey participants in the LCS programs about their impressions and experience with the scheduling and completing screening; conduct interviews with participants who receive an order for LCS but do not complete screening by their due date. 4. Interview LCS program directors and staff about barriers and facilitators of increasing screening rates in their programs.

Supporting Informed Decision Making About Multi-cancer Early Detection Testing

To develop a prototype participant educational aid that can be used by participants to support informed decision making about MCED testing. The aims of the pilot project include the following: 1. Conduct focus groups to explore preferences and concerns about MCED testing among adults of screening age. 2. Based on salient themes from focus group discussion, develop and administer surveys to explore preferences and concerns about MCED testing among adults of screening age. 3. Using findings from the focus groups and surveys, develop prototype patient educational aids about MCED testing following a user-centered design strategy.

A Study of PHST001 in Advanced Solid Tumors

Target Muscle Re-innervation and Regenerative Peripheral Nerve Interfaces Alone and in Combination for the Treatment of Residual and Phantom Limb Pain in Cancer Patients Who Have Received an Amputation

PRIMARY OBJECTIVE: Determine the relative effectiveness of three surgical techniques, TMR, RPNI, and TMR with RPNI, on chronic and phantom limb pain in the oncologic amputee using the validated Numerical Rating Scale (NRS) and Patient-Reported Outcomes Measurement Information System (PROMIS) Behavior, Intensity, Interference, and Global Health Forms. SECONDARY OBJECTIVES: I. To estimate the rate and total quantity of any pain medication use among oncology amputees who received one of the three surgical techniques. II. To estimate the rate of prosthetic use among oncologic amputees. III. To compare NRS and PROMIS among three surgical techniques to calculate the effect size and project the sample size which will be used to plan a multi-institutional study. OUTLINE: Patients are randomized to 1 of 3 arms. ARM 1: Patients undergo TMR procedure. ARM 2: Patients undergo RPNI procedure. ARM 3: Patients undergo TMR in combination with RPNI. After completion of study procedure, patients are followed up at 3, 6, and 12 months.

A First-in-Human Open-label, Phase I/Ib Dose Escalation and Expansion Cohort Study of EOS006215 as Monotherapy and in Combination With Pembrolizumab or Other Anticancer Treatments in Participants With Advanced Solid Tumors

The study will be conducted in 2 parts: - Part 1 - Dose Escalation Phase I dose escalation cohorts for EOS006215 as monotherapy and in combination with anticancer treatments in participants with specific tumor types. - Part 2 - Dose Expansion Phase Ib dose expansion cohort(s) may be included to further evaluate the safety, tolerability, efficacy, PK and PD of EOS006215 as monotherapy or in combination with anticancer treatments in participants with specific tumor types.

A Study to Learn About Study Medicine ALTA3263 in Adults With Advanced Solid Tumors With KRAS Mutations

This is an open-label, multicenter, Phase 1/1b study of ALTA3263, an orally bioavailable KRAS isoform-selective inhibitor that inhibits multiple mutant forms of KRAS, in adults with advanced solid tumor malignancies with KRAS mutations. This study will evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity of ALTA3263, and aims to find the best dose. The study consists of two parts: Part 1 - Dose Escalation and Part 1b - Dose Expansion.

Phase I Trial of 5-Fluorouracil (5FU) -Based Therapy in Combination With Hydroxytyrosol (HT) in Patients With Advanced or Metastatic Colorectal Cancer

Efficacy and Safety Study of Halneuron in the Treatment of Chemotherapy-Induced Neuropathic Pain