Pfizer B1371013 - Phase 2 PF-04449913 for Myelofibrosis

• Research type

  Research Study

• Full title

  A PHASE 2, DOUBLE-BLIND, RANDOMIZED SAFETY AND EFFICACY STUDY OF PF-04449913 VERSUS PLACEBO WITH DEFINED BEST SUPPORTIVE THERAPY ALLOWED IN BOTH ARMS IN PATIENTS WITH MYELOFIBROSIS PREVIOUSLY TREATED WITH ONE OR MORE JANUS KINASE INHIBITORS

• IRAS ID

  159374

• Contact name

  Claire Harrison

• Sponsor organisation

  Pfizer Inc. 235 East 42nd Street, New York, 10017

• Eudract number

  2014-001048-40

• Duration of Study in the UK

  3 years, 4 months, 4 days

• Research summary

  Myelofibrosis is a serious bone marrow disorder that disrupts the body's normal production of blood cells. The result is extensive scarring in the bone marrow, leading to severe anaemia, weakness, fatigue and often, an enlarged spleen and liver.

  Janus Kinase inhibitor(JAKi) works by targeting a certain pathway that may be causing cancer to grow, by stopping or inhibiting the cycle of development of the pathway. There is one JAKi that has been approved for the treatment of patients with myelofibrosis, called ruxolitinib.

  PF-04449913 is in a class of drugs known as hedgehog inhibitors and is designed to stop the growth of certain cancer stem cells which may be allowing cancer to grow. The hedgehog pathway is different from the JAK pathway. PF-04449913 is a small molecule inhibitor of the Sonic Hedgehog signalling pathway, which is currently under development for the treatment of haematologic malignancies and solid tumours.

  This Phase 2 study is conducted in two parts: a lead-in phase and a randomised phase. The lead-in phase (~20 participants) will be done to confirm that PF-04449913 100mg daily dose is safe and tolerated in patients with previously treated myelofibrosis. The double-blind randomised phase (~201 participants) will compare the effects of 100mg daily dose PF-04449913 versus placebo to find out which is better for treating patients with myelofibrosis who have been previously treated with one or more JAKi. Participants will be randomised 2:1 in the two treatment arms.

  Approximately 221 participants will be enrolled in this study at 70 different research sites in 11 countries.

  As part of this study participants will undergo:
  •Physical examinations, including manual palpation of the spleen and liver, and vital signs assessment;
  •Regular 12-led ECGs;
  •Blood sampling for laboratory analysis;
  •Health outcome assessment questionnaires;
  •Urinalysis and urine pregnancy testing.
  •Bone marrow aspirates and biopsies;
  •MRIs of abdomen (or CT if MRI is unsuitable)

• REC name

  London - Bloomsbury Research Ethics Committee

• REC reference

  14/LO/2150

• Date of REC Opinion

  10 Feb 2015

• REC opinion

  Further Information Favourable Opinion