Gout

Researchers are investigating the safety, tolerability, pharmacokinetics, and effectiveness of the drug IG3018 in people with high uric acid levels (hyperuricemia), including those with and without chronic kidney disease (CKD). This phase I/II clinical trial aims to better understand how IG3018 works in these groups and to explore appropriate dosing. The study is sponsored by Intelligem Therapeutics Australia Pty Ltd and includes participants aged 18 to 75 years. The trial has two parts. Part 1 is a randomized, double-blind, placebo-controlled dose escalation study in participants without CKD, testing increasing doses of IG3018 tablets (0.25 g, 0.5 g, and 1.0 g). Each dose cohort receives a single dose followed by four weeks of twice-daily maintenance dosing. Part 2 is an open-label study in participants with advanced predialysis CKD (Stages 3a, 3b, and 4), who receive either 0.5 g or 1.0 g of IG3018 twice daily for four weeks. Participants will attend study visits for blood and urine sample collection to analyze drug levels and kidney function. Safety and efficacy will be assessed through laboratory tests, gout attack monitoring, and uric acid measurements over about 46 days. The study tracks changes in serum uric acid levels, kidney function markers, and drug pharmacokinetics. Participants must provide consent and follow study procedures throughout the treatment and monitoring periods.

Researchers are studying pyrimidine and purine metabolism disorders (DPPMs), which affect how the body processes certain chemicals and can cause a range of symptoms from mild to severe, impacting the brain, blood, kidneys, and immune system. This research aims to better understand the causes, features, and outcomes of these disorders by comparing affected individuals, their unaffected family members, and healthy volunteers. The study focuses on both known and novel DPPMs and seeks to identify genomic, clinical, pharmacological, laboratory, and dietary factors influencing disease variability. Participants are divided into three groups: those diagnosed with DPPMs, their family members without the disorder, and healthy volunteers. Affected participants visit the clinic at least once a year, undergoing physical exams, sample collections (blood, urine, saliva, stool), and various tests depending on symptoms, which may include skin and mouth swabs, heart, kidney, brain, and nerve function tests, dental, hearing, and vision exams, learning assessments, physical activity monitoring, imaging scans, and photographs. These evaluations may be spread over up to seven days, and affected participants may remain in the study indefinitely. Family members and healthy volunteers have a single study visit with a physical exam and sample collections. Throughout the study, researchers collect DNA and biological samples for genetic, biochemical, enzyme, and microbiome analyses. The study includes detailed clinical and laboratory assessments to track disease features and variability. Participants' medical, laboratory, and imaging data are collected following standard care protocols. The primary outcome is to describe features of poorly characterized DPPMs, while secondary outcomes focus on identifying factors associated with different clinical results. The study involves long-term monitoring and may continue indefinitely for affected individuals.

Researchers are evaluating the effectiveness of dotinurad in reducing serum uric acid levels in adults with gout who cannot tolerate xanthine oxidase inhibitors (XOI) or who have not responded to uricase treatment. This Phase 2, randomized, double-blind, placebo-controlled study aims to better understand dotinurad's role in managing gout, particularly in those with previous treatment challenges. The study is sponsored by Crystalys Therapeutics and focuses on participants aged 18 to 75 years with a diagnosis of gout meeting specific criteria. Participants will be randomly assigned to one of two groups. One group will take dotinurad for 24 weeks, followed by an additional 12 weeks continuing dotinurad. The other group will receive a placebo for 24 weeks, then switch to dotinurad for the next 12 weeks. Dotinurad is given as oral over-encapsulated tablets, while the placebo contains inactive capsules. This two-part treatment period is designed to assess the drug's efficacy and safety over time. During the study, participants will have their serum uric acid levels measured at various points, including weeks 16, 20, 24, and up to week 40. Researchers will monitor the percentage of participants achieving specific uric acid level targets, changes from baseline, and any treatment-emergent or serious adverse events. The total study duration includes screening, treatment, and follow-up periods, allowing comprehensive evaluation of dotinurad's effects and safety profile in this population.

Researchers are studying the safety and tolerability of peguricase injections combined with methotrexate in adults with gout who have not responded well to standard uric acid-lowering treatments. This phase Ib trial also aims to understand how the drug behaves in the body and its initial effectiveness to help determine the best dose and treatment plan for future phase II trials. Participants receive peguricase injections in one of three dose groups: 4 mg, 8 mg, or 12 mg. Each group starts with a single dose followed by a 5-day safety observation. If no issues arise, participants then receive multiple doses combined with methotrexate, an oral medication at 15 mg. The multi-dose phase begins 2 to 4 weeks after the single dose phase. Each dose group includes 12 participants. Throughout the study, participants will be monitored for adverse and serious adverse events, and blood samples will be taken to measure how the drug is processed by the body. Researchers will track various markers including drug concentration over time and antibody responses for up to 14 weeks after the first dose. Participants must be able to attend all visits and complete assessments on schedule during the study period.

Researchers are evaluating the safety and performance of MagnetOs Putty and MagnetOs Easypack Putty, compared to autogenous bone graft, in patients undergoing hindfoot or ankle fusion surgeries. This phase IV post-marketing study focuses on treating hindfoot and ankle disorders, where synthetic bone graft extenders like MagnetOs products are routinely used by surgeons. The trial aims to assess bone fusion and functional outcomes in patients receiving these treatments. Patients will be randomly assigned to receive either MagnetOs Putty/Easypack Putty or a local autograft harvested from the calcaneus, distal tibia, or proximal tibia. Both treatments will be used with rigid hardware fixation during fusion surgeries such as ankle fusion, subtalar fusion, calcaneocuboid fusion, talonavicular fusion, or double fusion involving any two of these joints. The volume of MagnetOs or autograft used varies by joint, typically 1-5 cc for certain joints and up to 10 cc for the tibiotalar joint. Participants will be followed after surgery with visits at discharge and weeks 2, 6, 12, 24, and 52. Imaging evaluations, including radiographs and CT scans, will be performed at multiple time points to assess bone fusion and healing. The main outcome will be bone fusion measured by CT scan at 24 weeks post-operation. Additional assessments will include functional evaluations and further imaging up to one year post-surgery. Weight-bearing radiographs will begin at week 12, and safety monitoring will continue throughout the study period.

Researchers are studying the experiences of people who develop rheumatic immune-related adverse events (irAEs) after receiving immune checkpoint inhibitor immunotherapy. This study aims to understand how severe these events are, how they affect daily function, and the attitudes of patients towards different aspects of these side effects. The research focuses on conditions like arthritis and polymyalgia rheumatica that arise following this cancer treatment. This observational study does not involve any drug or treatment interventions. Instead, it gathers information through qualitative assessments from patients diagnosed by rheumatologists with inflammatory arthritis or polymyalgia rheumatica as irAEs after immune checkpoint inhibitor therapy. The study is sponsored by M.D. Anderson Cancer Center and will collect data over about one year. Participants will engage in interviews to share their experiences, which will help researchers evaluate the safety and adverse events associated with these immune-related conditions. The study includes monitoring adverse events throughout the study period. The total involvement duration averages one year, allowing for comprehensive understanding of the impact and progression of these rheumatic irAEs.

Researchers are evaluating an investigational drug called NNC4004-0002 to see if it can lower serum uric acid levels safely in adults with asymptomatic hyperuricemia. This is a Phase 1, double-blinded, placebo-controlled study where the safety and tolerability of a single dose of NNC4004-0002 will be tested for the first time in humans. The study aims to understand how the body handles this new medicine and its effects over time. Participants will receive either a single ascending dose of NNC4004-0002 or a matching placebo, both given as injections under the skin. The study includes up to six groups, each receiving different doses to assess safety and dose effects. Depending on the dose, participants may receive more than one injection. The study will last about 19 months in total, with each participant involved for approximately 7 months. During the study, participants will visit the clinic about 14 times, including a 4-night stay at the clinic. Researchers will monitor for any adverse events, measure the drug levels in the blood up to 72 hours after dosing, assess kidney clearance, and track changes in serum uric acid from baseline until about 28 weeks after dosing. Safety tests, physical exams, and lab tests will be conducted to ensure participant well-being throughout the study period.

Researchers are evaluating the effectiveness of dotinurad compared to allopurinol in lowering serum uric acid levels in adults with hyperuricemia related to gout. This phase 3, randomized, double-blind study focuses on adults aged 18 to 75 who have had gout for at least one year and experienced at least two gout flares in the past year. The study aims to measure how well dotinurad lowers serum uric acid at 24 weeks compared to allopurinol. Participants will stop their current allopurinol treatment and be assigned to one of three groups: continuing allopurinol at the same dose once daily for 64 weeks, starting dotinurad 1 mg daily for four weeks then 2 mg daily through week 64, or starting dotinurad 1 mg daily for four weeks, 2 mg daily for eight weeks, and then 4 mg daily through week 64. Both dotinurad and allopurinol are given as oral tablets. This treatment period is followed by ongoing monitoring up to week 68. During the study, participants will have regular visits to assess serum uric acid levels and record gout flares needing treatment. Safety will be monitored by tracking adverse events throughout the study. The main outcome is the percentage of participants achieving serum uric acid levels below 6.0 mg/dL at week 24. Other measures include gout flare rates, changes in uric acid levels over time, and safety assessments. The total participation time spans from screening through week 68, including treatment and follow-up visits.

Researchers are evaluating PRX-115, a recombinant pegylated Uricase given by intravenous infusion, for its safety, effectiveness, and best dosing schedule in adults with gout who have not normalized their serum uric acid levels despite treatment or cannot use standard drugs. This phase II, randomized, double-blind, placebo-controlled study compares infusions of PRX-115 with or without methotrexate to placebos over 24 weeks. The study is led by Protalix and aims to better understand PRX-115's impact on gout and its tolerability. Participants receive PRX-115 through intravenous infusions at varying intervals: every 4, 6, or 8 weeks, combined with either methotrexate or placebo methotrexate, or they receive placebo infusions on similar schedules. The study includes multiple dosing groups to find the optimal regimen, with up to six doses over 24 weeks depending on the schedule assigned. Methotrexate is given orally once a week at 15 mg where applicable. During the study, participants undergo regular monitoring including serum uric acid tests to measure treatment response, safety assessments, and evaluations of drug behavior in the body. Researchers track the percentage of participants who maintain serum uric acid below 6 mg/dL at 6 months as the primary outcome. Additional safety and tolerability data are collected for up to 8 months. The overall participation period covers treatment and follow-up to assess long-term effects and adverse events.

Researchers are evaluating the effectiveness of antigravity treadmill training and body weight-supported treadmill training for rehabilitation in elderly patients aged 60 to 75 years who have recently undergone hip or knee replacement surgery. The study compares these two methods to conventional gait training to see which approach may better support recovery and walking ability after surgery. Participants will be randomly assigned to one of three groups: antigravity treadmill training, body weight-supported treadmill training, or conventional rehabilitation. Each group will undergo a 6-week program with five sessions per week. The antigravity treadmill uses air pressure to reduce weight on joints with gradually decreasing support, while the body weight-supported treadmill uses a harness to partially offload weight with a steady level of support. The conventional group receives standard postoperative therapy including gait training and physical therapy techniques. During the study, participants will receive comprehensive daily therapy including kinesitherapy, ergotherapy, and individualized physical therapy procedures. Researchers will assess outcomes such as pain and function using the Western Ontario and McMaster Universities Osteoarthritis Index, balance, mental health, stress, and walking parameters both before and after the 6-week intervention. The total participation period includes baseline assessments and the 6-week therapy program under professional supervision.