Clinical Trials and You. Annette Czernik, MD, FAAD Icahn School of Medicine at Mount Sinai

Transcription

1 Clinical Trials and You Annette Czernik, MD, FAAD Icahn School of Medicine at Mount Sinai

2 King Nebuchadnezzar ruled Babylon until 562 BCE (according to The Bible) Purpose and history of clinical trials

3 King Nebuchadnezzar ruled Babylon until 562 BC (according to The Bible) Purpose and history of clinical trials

4 First change in public health policy based on clinical trial data Higher intake of legumes is linked to a 35% reduction in diabetes A diet high in plant protein is linked to lower risk of heart disease, diabetes and obesity Purpose and history of clinical trials

5 Correlation does not equal causation Clinical trial is a study conducted by researchers on human subjects to test medical treatment or prevention strategy Purpose and history of clinical trials

6 Prevention Strategy Lifestyle change Dietary modifications Health education Medical Treatment Drug Surgical procedure Medical device Therapy Purpose and history of clinical trials

7 Scurvy putrid gums, the spots and lassitude, weakness of the knees Same rations Treatment: cider, acid, vinegar, seawater, nutmeg and barley, oranges and lemons Dr James Lind Purpose and history of clinical trials

8 Treatment group(s) Bias Blinding Double-blind study Randomization Endpoints Sample size Control (placebo) group Allow comparison Group characteristics and risk factors should be equal to treatment group Crossover Purpose and history of clinical trials

9 Clinical Trial Phases Phase I - evaluates safety, dose and side effects Phase II - evaluates efficacy Phase III confirms efficacy in larger group Phase IV post-market studies, affects on different populations and side effects of long-term use Purpose and history of clinical trials

10 1947 Nuremberg Code 1964 Declaration of Helsinki 1979 Belmont Report 1996 Good Clinical Practice Ethical advances

11 In 1892, Osler wrote the Principles and Practice of Medicine Prevailing medical text for over 50 years Medicine was a descriptive science Anatomy and clinical manifestations Little was known of etiology or treatment Bloodletting Benefits of clinical trials participation

12 Dermatology trials are lacking Immunobullous disease based on expert opinion Trials in pemphigus and pemphigoid Rarity and severity of disease Limited sample size Greater error and bias Benefits of clinical trials participation

13 Advancing the field Potential for cutting edge treatments Often no out of pocket expenses Greater monitoring Benefits of clinical trials participation

14 Clinicaltrials.gov Enter diagnosis and location Lists trial data if available near you Clinical trials near you

15 PEMPHIGUS STUDIES A RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, ACTIVE-COMPARATOR, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF RITUXIMAB VERSUS MMF IN PATIENTS WITH PEMPHIGUS VULGARIS A SAFETY STUDY OF SYNT001 IN SUBJECTS WITH PEMPHIGUS (VULGARIS OR FOLIACEOUS) POLYCLONAL REGULATORY T CELLS (POLYTREGS) FOR PEMPHIGUS Clinical trials near you

16 INCLUSION CRITERIA Moderate to severe pemphigus vulgaris Diagnosed within 24 months On prednisone mg/ day Phase III ENDPOINTS Evaluate the efficacy and safety of rituximab compared to MMF Safety follow up 48 weeks A RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, ACTIVE-COMPARATOR, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF RITUXIMAB VERSUS MMF IN PATIENTS WITH PEMPHIGUS VULGARIS

17 PEMPHIX Study Design- Phase III Active Comparator Superiority Trial Study Objec,ves To evaluate the efficacy and safety of rituximab compared to MMF in PV pa,ents. Cor,costeroid- related AEs in rela,on to cor,costeroid exposure will also be assessed Stratified according to duration since diagnosis: 1 year vs. > 1 year Region: North America vs. RoW CS = corticosteroid (prednisone or equivalent); IV = intravenous; MMF = mycophenolate mofetil; PO = by mouth; PV = pemphigus vulgaris; Q12H = every 12 hours; RTX = rituximab; SFU = safety follow-up. a Administrations of the first dose of study treatment (Day 1) should occur within 24 hours following the baseline assessments. However, administration up to 72 hours will be allowed when necessary. b Primary efficacy endpoint; sustained complete remission, evaluated by PDAI is to be measured at Week 52

18 INCLUSION CRITERIA Pemphigus vulgaris or foliaceous Open label 5 weekly IV infusions Phase I ENDPOINTS Safety Tolerability Pharmacokinetics/ dynamics Immunogenicity Pemphigus Ab levels Follow up 16 weeks A SAFETY STUDY OF SYNT001 IN SUBJECTS WITH PEMPHIGUS (VULGARIS OR FOLIACEOUS)

19 Pemphigus & SYNT001 Pemphigus is has pathogenic autoantibodies FcRn enables these autoantibodies to persist SYNT001 targets FcRn It is predicted to dismantle and eliminate the inflammatory activities of IgG, including autoantibodies in pemphigus

20 INCLUSION CRITERIA Pemphigus vulgaris or foliaceous Open label a single IV infusion of Tregs Anticipated start date Sept 2017 Phase I ENDPOINTS Safety Effect of Treg therapy Follow up 52 weeks POLYCLONAL REGULATORY T CELLS (POLYTREGS) FOR PEMPHIGUS

21 PEMPHIGOID STUDY EVALUATION OF SAFETY, EFFICACY AND PHARMACODYNAMIC EFFECT OF BERTILIMUMAB IN PATIENTS WITH BULLOUS PEMPHIGOID Clinical trials near you

22 INCLUSION CRITERIA 60 years old Bullous pemphigoid Newly diagnosed Moderate to extensive disease Open label (3 infusions of bertilimumab over 1 month) ENDPOINTS Safety Efficacy Pharmacokinetics/ dynamics Follow up 13 weeks EVALUATION OF SAFETY, EFFICACY AND PHARMACODYNAMIC EFFECT OF BERTILIMUMAB IN PATIENTS WITH BULLOUS PEMPHIGOID

23 Anti-eotaxin-1 Inhibits eosinophils Bullous pemphigoid high concentration of esinophils within lesions EVALUATION OF SAFETY, EFFICACY AND PHARMACODYNAMIC EFFECT OF BERTILIMUMAB IN PATIENTS WITH BULLOUS PEMPHIGOID

24 What are clinical trials? How are they structured? How will I benefits from participation? Are there clinical trials in my area? Conclusion

25 Thank you