Pizzicato Study: A Phase 2A, double-blind, randomized, placebo-controlled, parallel group study to evaluate the efficacy and safety of oral PF-06651600 AND PF-06700841 as induction and open label extension treatment in patients with moderate to severe...
Published: 05/24/2018
General Information:
Full Title Study: Pizzicato Study: A Phase 2A, double-blind, randomized, placebo-controlled, parallel group study to evaluate the efficacy and safety of oral PF-06651600 AND PF-06700841 as induction and open label extension treatment in patients with moderate to severe Crohn's disease
To evaluate the effectiveness of study drug PF 06651600 and study drug PF 06700841 compared to placebo (harmless pill) at Week 12 in participants with moderate to severe Crohn's Disease.
Eligibility:
Inclusion criteria:
- Adult > 18 years < 75 years (For Korea >19 and < 75 years)
- Diagnosis of Crohn's Disease at least 3 months ago
- must have inadequate (poor) response, loss of response or intolerance to traditional Crohn's treatment (steroids, Immunosuppressants (AZA, 6-MP, or MTX); Anti TNF inhibitors (eg, infliximab, adalimumab, or certolizumab); Anti-integrin inhibitors (eg, vedolizumab), Anti_IL_12/23 inhibitor (ustekinumab)
- Current treatment for Crohn's must be stable (same) dose 2- 4 weeks prior to starting study treatment (study drug)
Study Details:
Study Description
- Eligible patients will have at least 15 site visits over approximately 18 months (74 weeks).
- There will be a screening period of up to 6-weeks. Then there is a 12 week induction phase where you will be assigned by chance (like the flip of a coin or drawing straws) to receive either PF-06651600 (study drug), PF-06700841 (study drug) or placebo (no active drug).
- After 12 weeks, all participants will receive one of the two study drugs (no placebo) possibly at a lower dose for 52 weeks.
- Finally, there will be a 4-week follow up period.
To learn more, click here or visit the Pizzicato Study site.
Description of Treatment or Intervention (Mechanism of Action)
PF-06651600 and PF-06700841 are investigational drugs. PF-06651600 is in a class called JAK3 inhibitors, which could be helpful in treating Crohn's disease (CD). PF-06700841 is in a class called TYK2 and JAK1 which together could be helpful in treating CD. PF-06651600 and PF-06700841 may decrease the inflammation and ulceration of CD by inhibiting production of cytokines (small proteins) which are thought to be key drivers of the disease. PF-06651600, PF-06700841 or placebo will be taken as oral tablets. These compounds inhibit either JAK3 or JAK1 and TYK2. As these kinases are required for transduction of cytokine signaling, blockade of these will result in decreased inflammation.
Patient Participation Requirements
- Eligible patients will have at least 15 site visits. The duration of participation of eligible patients will be approximately 18 months (74 weeks).
- Written informed consent must be obtained prior to performance of any protocol-specific procedures. Patients will be screened to confirm that they meet all inclusion/exclusion criteria for the study.
- Screening procedures include: Hearing test, ECG, vital signs, height, weight, complete medical history, medication history, and prior treatment for Crohn's Disease. A complete physical examination will be performed including collection of blood, urine, and stool samples. Women of childbearing potential will be tested for pregnancy and will need to adhere to strict contraception requirements throughout the study. You will have a chest X-ray, if you have not had one in the last 3 months. A screening endoscopy (colonoscopy) will be performed if it has not been done in the last 8 weeks.
- There is a 12 week induction phase where you will be assigned by chance (like the flip of a coin or drawing straws) to receive either PF-06651600, PF-06700841 or placebo. After 12 weeks, all participants will receive one of the two study drugs (no placebo) possibly at a lower dose for 52 weeks. Finally, there will be a 4-week follow up period.
- Throughout the study safety testing such as ECGs, hearing tests will be performed as well as blood and stool samples will be collected periodically for safety, effectiveness, and exploratory assessments. An additional endoscopy will be performed at week 12 and at week 64, after which participants will enter the follow-up period.
- Participants will be required to keep an electronic diary beginning with the first screening visit and ending at the final study visit. Participants will record information daily on their stool frequency and rectal bleeding. There will be quality of life questionnaires to complete throughout the study.
Possible Risks & Side Effects
Risks and side effects:
- PF-06651600 (Study Drug): may cause diarrhea, headache and erythema. May cause rashes or infections.
- PF-06700841 (Study Drug): may cause headache, constipation. May cause infections.
- At this time, the effects of PF-06700841 on male and female fertility, and pregnancy in humans, and effects on fetus or a nursing child are not known. For this reason strict use of birth control must be followed.
- Both PF-06651600 and PF-06700841 are investigational, so there may be other risks that are unknown.
Placebo Risk:
- Certain research participants in this research study will receive a placebo. Taking a placebo may be similar to not taking any medication. If you are one of the people who receive a placebo, your Crohn's Disease (CD) may stay the same or get worse, or your CD may suddenly get better just as it may have done without additional treatment.
Risks related to study procedures:
- Blood draws: A blood draw may cause faintness, inflammation of the vein, pain, bruising, or bleeding at the site of puncture.
- ECG: The risks from an ECG can include skin irritation and a rash from the gel that is used or from wearing or removing the patches.
- Hearing test (audiogram): no risks associated with having an audiogram.
- Chest X-ray: The amount of radiation from a chest x-ray will be about 0.1 millisievert (mSv). There is no significant risk from this total amount of radiation.
- Endoscopy (Colonoscopy): Complications of this procedure are very uncommon and may include bleeding and perforation (tear or hole in the bowel).
- Tissue biopsies: Small pinches of tissue from the intestine will be taken during endoscopy and may cause potential minor bleeding. You will not feel any pain from this.