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Clinical Trials
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Phase II trials are performed in the specific patient population for which the drug is being developed. The subjects receive the dose that was identified as optimal in phase I, and data is gathered on efficacy and safety and, often, also on more exploratory aspects such as biomarkers for prediction of efficacy or toxicity. The number of subjects required for reliable interpretation of the results in phase II is usually less than 100.
Designing and Running a Clinical Trial
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
We now concentrate on clinical trials giving a brief overview of trial set up and the running of a trial. Clinical trials are generally categorised into four phases. These are, Phase I Trials are “first in man” trials. Drugs will have been developed in a laboratory and then tested on animals, before trying them out on humans. They involve a small number of subjects, often healthy volunteers.Phase II Trials are relatively small trials, generally ranging from 30 to 120 patients, that glean more information about the safety and efficacy of the drug or treatment being tested, and help set the dose level for a Phase III trial.Phase III Trials are confirmatory trials, in that they are designed to give a definitive answer to the hypothesis being tested, for example “Does this new cancer drug increase the median survival time of patients compared to the existing treatments?” A sample size of 500 to 1000 patients is not uncommon, with many centres involved in collecting the patient data.Phase IV Trials are run after a drug has been licenced to collect data on the long-term effects of the drug.
Translation of Tissue Engineering Approach from to Clinics
Published in Vincenzo Guarino, Marco Antonio Alvarez-Pérez, Current Advances in Oral and Craniofacial Tissue Engineering, 2020
Daniel Chavarría-Bolaños, José Vega-Baudrit, Bernardino Isaac Cerda-Cristerna, Amaury Pozos-Guillén, Mauricio Montero-Aguilar
RCTs are classified according to their purpose and should follow a specific order. Phase I studies are designed to test the safety and maximum tolerated dose (when testing a drug). Since this will be the first contact of the experimental product with humans, this study design usually involves a small number of healthy test subjects (20–100) and the product is open-labeled. Volunteers are very closely monitored for signs of toxicity and, bioethical issues must be especially addressed during informed consent, in order to avoid the misconception that participants will receive a therapeutic intervention. The FDA estimates that approximately 70% of these studies move to the next phase. Phase II trials also include a small number of volunteers (100–300), but unlike Phase I, participants have the condition or disease of interest. This design is used to understand more of the pharmacokinetics and the pharmacodynamics of the tested product including optimal doses, frequency of intake, administration routes and endpoints. These trials could be designed to provide valuable information for a much larger Phase III trial. Phase II trials will use some exploratory methods to understand the therapeutic efficacy of the product, but since only a small number of participants are recruited, they lack statistical power to infer any effect. FDA reports that 33% of Phase II studies will move to the next phase, and usually sponsors, researchers and the regulatory agency will meet at this point to discuss the preliminary data, IND, methodology of Phase III trials and any safety concerns (Umscheid et al. 2011).
Drugs in phase I and II clinical development for the prevention of stroke in patients with atrial fibrillation
Published in Expert Opinion on Investigational Drugs, 2021
Robert Bentley, Lewis J. Hardy, Laura J Scott, Parveen Sharma, Helen Philippou, Gregory Y. H. Lip
In order to gain more confidence in the efficacy and safety of the novel therapeutics discussed here, it is essential that when phase II trials proceed to phase III, the selected patient cohorts accurately represent the observed patient population in terms of age, gender, race, existing comorbidities, and long-term therapeutic use. This will provide more realistic safety and efficacy data and result in greater understanding of the novel anticoagulants, ASOs, mAbs, and small molecule anticoagulants. There appears to be great potential for these new therapeutic avenues; however, due caution must be used and safety and efficacy profiles diligently obtained to ensure patient safety. Should there be superior safety and efficacy within the novel FXI and FXII inhibiting therapeutics compared to the NOACs, it is very likely that the new generation of anticoagulants could replace standard existing therapies.
The role of immune checkpoint inhibitors in advanced non-small cell lung cancer
Published in Expert Review of Respiratory Medicine, 2019
Nikolaos F Pistamaltzian, Vassilis Georgoulias, Athanasios Kotsakis
Nivolumab, a fully humanized IgG4 antibody, was the first ICI approved for second-line treatment of NSCLC. Following the above-mentioned trial, its clinical development evolved into phase II trials. CheckMate-063, a single-arm phase II trial, evaluated efficacy and safety of nivolumab in patients with advanced, refractory, squamous NSCLC. In this trial, 117 patients were treated with nivolumab every 2 weeks. The Objective Response Rate (ORR) was 14.5%, with a median OS of 8.2 months, and a 1-year survival rate of 40.8%. Tumor samples were assessed for PD-L1 in two-thirds of the patients, and a cut of point of 5% was considered as threshold for positivity. Patients with >5% PD-L1(+) tumor cells fared better in terms of response compared to patients with <5% PD-L1(+). Grade 3–4 treatment-related adverse events (TRAE) occurred in about a sixth of patients, most commonly fatigue, pneumonitis, and diarrhea [20,21].
A comparison of human natural monoclonal antibodies and aptamer conjugates for promotion of CNS remyelination: where are we now and what comes next?
Published in Expert Opinion on Biological Therapy, 2018
Maria K. Perwein, John A. Smestad, Arthur E. Warrington, Robin M. Heider, Mark W. Kaczor, Louis J. Maher, Bharath Wootla, Ahmad Kunbaz, Moses Rodriguez
One important aspect is how efficacy will be measured in patients as to their effect on promoting remyelination either by aptamers or antibodies. Phase I trials will be focused on treating patients with gradually increasing dosage of antibody or aptamer to determine possible toxicity. This has already been performed in the Phase I trials with rHIgM22. Phase II trials will be focused on determining clinically significant endpoints based on the clinical deficits of the patients. Therefore if the patient is presenting with optic neuritis then visual acuity, color vision, visual evoked responses, visual fields will be used as relevant endpoints. If the patient presents with motor deficits then increase in motor power, improved gait speed in a 25 foot gait analysis, 9 peg hole test in a patient with upper motor strength will be used. In patients with sensory deficits, a somatosensory evoked response test can be a non-biased approach to showing improvement since clinical sensory testing in patients may have bias. In all of these situations, patients with acute attacks not responding to conventional intravenous steroids will be first tested to see if the aptamer or antibodies improve function. If there is an effect on patients with acute attacks, then the aptamer or antibodies may be tried on patients with progressive deficits. The endpoints in these situations will likely be at 2 or 3 years following therapy. The issue of proving remyelination will be dependent on showing changes by newer methods of MRI, such as MTR and diffusion tensor imaging. The Phase III trials will be dependent on the findings in the Phase II trials.