Onderzoek met geneesmiddelen

Fases onderzoek Fase I: veiligheid Fase II: Doeltreffendheid Fase III: I en II op grote schaal Fase IV: Opvolging van het geneesmiddel

overview of Tofacitinib UC Clinical development program

Tofacitinib UC Phase 3 Program OCTAVE Induction 1 Randomization Assessment 10 mg BID Nonresponders Placebo OCTAVE Sustain OCTAVE Open Responders† 8 weeks* N=598 (4:1) Re-randomization Assessment Enrollment Assessment 10 mg BID 5 mg BID‡ Completers & Treatment Failures 5 mg BID 10 mg BID‡ OCTAVE Induction 2 Placebo Randomization Assessment 52 weeks* N=593 (1:1:1) Responders† 10 mg BID Up to 1st approval Estimated N=944 Placebo 8 weeks* N=541 (4:1) Nonresponders * Final complete efficacy assessment at Week 8/52. Treatment continued up to Week 9/53. † “Responders” refers to subjects who achieved clinical response during OCTAVE Induction 1 or 2. ‡ Subjects in remission at Week 52 of OCTAVE Sustain were assigned to tofacitinib 5 mg BID; subjects who completed 8 weeks of treatment in OCTAVE Induction 1 or 2 and were classified as nonresponders, and subjects who completed OCTAVE Sustain but did not meet remission criteria or who withdrew from the study early due to treatment failure, were assigned to tofacitinib 10 mg BID. BID=twice daily; UC=ulcerative colitis. 1. Clinicaltrials.gov. NCT01465763. 2. Clinicaltrials.gov. NCT01458951. 3. Clinical trials.gov. NCT01458574. 4. Clinicaltrials.gov. NCT01470612. 5. Pfizer data on file.

Key Inclusion and Exclusion Criteria Inclusion Criteria Exclusion Criteria ≥18 years old with diagnosis of UC ≥4 months prior to screening Moderate to severe active UC defined by baseline total Mayo score ≥6, with rectal bleeding subscore ≥1, and endoscopic subscore ≥2 Based on central endoscopy reading History of failure or intolerance to ≥1 of the following therapies: Oral or intravenous corticosteroids Azathioprine or 6-MP TNF inhibitors Patients permitted to use the following medications for UC: Oral 5-ASA or sulfasalazine with stable dose ≥4 weeks prior to baseline Oral corticosteroids (prednisone up to 25 mg/day; budesonide up to 9 mg/day) with stable dose ≥2 weeks prior to baseline Chronic treatment with antibiotics with stable dose ≥2 weeks prior to baseline Indeterminate, microscopic, ischemic, or infectious colitis; or clinical findings suggestive of Crohn’s disease Disease limited to distal 15 cm No previous treatment for UC (ie, treatment naive) Signs of fulminant colitis or toxic megacolon Inadequate washout for the following medications prior to baseline: Azathioprine, 6-MP, MTX within 2 weeks TNF inhibitors or interferon therapy within 8 weeks Cyclosporine, mycophenolate mofetil/mycophenolic acid, or tacrolimus within 4 weeks Intravenous corticosteroids within 2 weeks Rectally administered corticosteroid or 5-ASA within 2 weeks Anti-adhesion molecule therapy within 1 year 5-ASA=5-aminosalicylic acid; 6-MP=6-mercaptopurine; MTX=methotrexate; TNF=tumor necrosis factor; UC=ulcerative colitis. A3921094 and A3921095 Final Protocols.

178 ziekenhuizen in 23 landen: 2011-2015 Dubbel blind placebogecontroleerde RCT

Eindpunten Primaire eindpunt: Major secondaire eindpunt: Klinische respons na week 6: afname 100 ptn CDAI score / CDAI <150 Major secondaire eindpunt: Klinische remissie na week 8 (CDAI <150) Klinische respons na week 8 Afname van baseline CDAI van ≥ 70 ptn op week 3 en 6

Studies in LUMC Stamcellen bij proctitis Poeptransplantatie (later in 2018) Dosis verlaging adalimumab Monitoren bijwerkingen diverse medicamenten …….