A Study of Guselkumab in Participants With Familial Adenomatous Polyposis | oneFAPvoice

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A Study of Guselkumab in Participants With Familial Adenomatous Polyposis

study id #: NCT03649971

condition: Adenomatous Polyposis Coli

status: recruiting

purpose:

The purpose of this study is to determine the effect of treatment with guselkumab in participants with familial adenomatous polyposis (FAP) on rectal/pouch polyp burden.

intervention: Guselkumab, Placebo

start date: November 19, 2018

estimated completion: August 31, 2020

last updated: February 28, 2019

phase of development: Phase 1

size / enrollment: 72

primary outcomes:

  • Percentage Change from Baseline in Rectal/pouch Polyp Burden at Week 24 [ Time Frame: Baseline, Week 24 ]
    Percentage change from baseline in rectal/pouch polyp burden (sum of the polyp diameters) at Week 24 will be determined through endoscopy.

secondary outcomes:

  • Percentage Change from Baseline in Number of Colorectal Polyps [ Time Frame: Baseline, Weeks 24 and 52 ]
    Percentage change from baseline in number of colorectal polyps will be determined.
  • Percentage Change from Baseline in Number of J-pouch Polyps [ Time Frame: Baseline, Weeks 24 and 52 ]
    Percentage change from baseline in number of J-pouch polyps will be determined.
  • Percentage Change from Baseline in J-pouch Polyp Burden [ Time Frame: Baseline, Weeks 24 and 52 ]
    Percentage change from baseline in J-pouch polyp burden (sum of polyp diameters) will be determined.
  • Percentage Change from Baseline in Number of Duodenal Polyps [ Time Frame: Baseline, Weeks 24 and 52 ]
    Percentage change from baseline in number of duodenal polyps will be determined.
  • Percentage Change from Baseline in Duodenal Polyp Burden [ Time Frame: Baseline, Weeks 24 and 52 ]
    Percentage change from baseline in duodenal polyp burden (sum of polyp diameters) will be determined.
  • Change in International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Stage [ Time Frame: Baseline, Weeks 24 and 52 ]
    Change in InSiGHT stage will be determined. Various stages of InSiGHT staging system are defined as: Stage 0: 0-10 polyps, all less than (<)5 millimeter (mm); Stage 1: 10-25 polyps, most < 5 mm, none greater than (>) 1 centimeter (cm); Stage 2: 10-25 polyps, any > 1 cm, amenable to complete removal; Stage 3: > 25 polyps amenable to complete removal, or any incompletely removed sessile polyp, or any evidence of High-Grade Dysplasia (HGD), even if completely excised; and Stage 4: > 25 polyps amenable to complete removal, or any incompletely excised sessile polyp showing HGD, any invasive cancer).
  • Change in Spigelman Stage Score [ Time Frame: Baseline, Weeks 24 and 52 ]
    Change in Spigelman stage score will be determined. Spigelman classification system measures risk of developing duodenal cancer in familial adenomatous polyposis (FAP). It has been classified in following stages- Stage 0 (0 points); Stage 1 (1-4 points); Stage 2 (5-6 points); Stage 3 (7-8 points); and Stage 4 (9-12 points). The total score ranges from 0 to 12. Points are accumulated for polyps' number, size, histology and severity of dysplasia. Stage 1 indicates mild disease, whereas stage 3-4 indicates severe duodenal polyposis.
  • Trough Concentration of Guselkumab [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    Serum samples will be analyzed to determine trough concentrations of guselkumab using a validated specific, and sensitive method.
  • Number of Participants with Anti-guselkumab Antibodies [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    Number of participants with Anti-guselkumab antibodies will be determined.
  • Anti-guselkumab Antibodies Serum Titers [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed positive samples will be reported.
  • Number of Participants with Adverse Events as a Measure of Safety [ Time Frame: From Screening up to 52 Weeks ]
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
  • Number of Participants with Vital Sign Abnormalities as a Measure of Safety and Tolerability [ Time Frame: From Screening up to 24 Weeks ]
    Number of participants with vital sign abnormalities will be reported. Vital signs includes temperature, pulse/heart rate, respiratory rate and blood pressure.
  • Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability [ Time Frame: From Screening up to 24 Weeks ]
    Number of participants with clinical laboratory abnormalities will be reported. Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.
  • Relative Changes to Baseline in Levels of Interleukin (IL)-23 Effector Proteins in Biopsy Tissue [ Time Frame: Baseline, Weeks 12 and 24 ]
    Relative Changes to Baseline in levels of IL-23 effector proteins in biopsy tissue will be measured.

inclusion criteria:
• Phenotypic familial adenomatous polyposis (FAP) with disease involvement of the colorectum by either genetic or clinical diagnosis: Adenomatous polyposis coli (APC) germline mutation with or without family history, or with greater than (>)100 adenomas in large intestine and a family history of FAP, attenuated FAP is allowed. FAP phenotype post colectomy for polyposis with a family history of FAP may be allowed
• Post-colectomy or subtotal colectomy
• Polyps with a sum of diameters greater than or equal to (>=)10 millimeter (mm) in the rectum or pouch on biopsy at screening
• A woman of childbearing potential must agree not to get pregnant during the study and at least 12 weeks after the last dose of study administration
• A woman must agree not to breast feed or donate eggs (ova, oocytes) during the study and for a period of 12 weeks after the last administration of study drug

exclusion criteria:
• Prior use of any biologic therapy targeting interleukin (IL)-12/23, IL-17, or IL-23 receptor
• Use of non-steroidal anti-inflammatory drugs other than aspirin during the study. The use 81 milligram (mg) of aspirin a day or 650 mg of aspirin per week is allowed
• Treatment with other FAP-directed drug therapy (including NSAID [Nonsteroidal anti-inflammatory drug] drugs), unless completes a 4-week washout period prior to randomization
• Duodenum or colon/rectum/pouch with high grade dysplasia or cancer on biopsy at screening
• Duodenal or colorectal polyp >1 centimeter (cm) not excised at the screening evaluation

sponsor: Janssen Research & Development, LLC

contacts: Study Contact: 844-434-4210, JNJ.CT@sylogent.com

investigators: Janssen Research & Development, LLC Clinical Trial

locations: United States