Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Guselkumab in Participants With Familial Adenomatous Polyposis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03649971
Recruitment Status : Recruiting
First Posted : August 28, 2018
Last Update Posted : December 30, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE August 27, 2018
First Posted Date  ICMJE August 28, 2018
Last Update Posted Date December 30, 2020
Actual Study Start Date  ICMJE November 19, 2018
Estimated Primary Completion Date July 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2019)
  • 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, 24, 32, 40, and 48 ]
    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, 24, 32, 40, and 48 ]
    Number of participants with Anti-guselkumab antibodies will be determined.
  • Anti-guselkumab Antibodies Serum Titers [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48 ]
    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 60 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 52 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 52 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, 24, and 52 ]
    Relative Changes to Baseline in levels of IL-23 effector proteins in biopsy tissue will be measured.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2018)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Guselkumab in Participants With Familial Adenomatous Polyposis
Official Title  ICMJE A Phase 1b, Multicenter, Randomized, Blinded, Placebo-controlled Study to Evaluate the Efficacy of Guselkumab in Subjects With Familial Adenomatous Polyposis
Brief Summary 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.
Detailed Description Familial adenomatous polyposis (FAP) is the most common polyposis syndrome. It is autosomal dominant inherited disorder characterized by early onset of hundreds to thousands of adenomatous polyps throughout colon. If left untreated, this syndrome may develop colorectal cancer (CRC). Polyps from individuals with FAP display inflammatory features associated with activation of interleukin (IL) 23/IL 17/JAK/STAT3 pathway. This inflammation is thought to contribute to further mutagenesis, culminating in tumor development. Specifically, IL-23 is linked to tumor growth and progression in CRC. Guselkumab is a human immunoglobulin monoclonal antibody directed against p19 subunit of IL-23, specifically targets IL-23 and inhibits its interaction with IL-23 receptor, inhibiting IL 23 specific intracellular signaling and subsequent cell activation and cytokine production, which result in less inflammation and reduce tumor development. The clinical hypothesis of this study is that treatment with guselkumab will reduce rectal/pouch polyp burden compared with baseline in active arms compared with placebo. The study is designed to determine if guselkumab has clinical activity in colorectum and duodenum, by reducing number of polyps over a period of 24 weeks. Participants will be randomized to 1 of 3 treatment arms (Guselkumab 100 mg [milligram] SC [subcutaneous], Guselkumab 300 mg SC, and placebo SC). Efficacy evaluations include rectal/pouch polyp burden assessment, biomarker analysis include discrete IL-23 signaling effector proteins (IL-23R, pSTAT3, Il-17A) and safety evaluations will include monitoring of adverse events, laboratory tests, vital sign measurements, and physical examination. Safety will be monitored throughout study (up to Week 60).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Adenomatous Polyposis Coli
Intervention  ICMJE
  • Drug: Guselkumab
    Guselkumab SC will be administered every 4 weeks.
    Other Name: Tremfya
  • Drug: Placebo
    Placebo SC will be administered every 4 weeks.
Study Arms  ICMJE
  • Experimental: Guselkumab Dose 1
    Participants will receive guselkumab Dose 1 subcutaneous (SC), 6 doses every 4 weeks from Week 0 to Week 20. Participants who respond to guselkumab may continue treatment at the same dose level through Week 48.
    Intervention: Drug: Guselkumab
  • Experimental: Guselkumab Dose 2
    Participants will receive guselkumab Dose 2 SC, 6 doses every 4 weeks from Week 0 to Week 20. Participants who respond to guselkumab may continue treatment at the same dose level through Week 48.
    Intervention: Drug: Guselkumab
  • Placebo Comparator: Placebo
    Participants will receive placebo SC, 6 doses every 4 weeks from Week 0 to Week 20.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 27, 2018)
72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 28, 2022
Estimated Primary Completion Date July 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 100 milligram (mg) of aspirin a day or 700 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
  • High grade dysplasia or cancer on biopsy at screening in GI tract (including stomach, duodenum, and colon/rectum/pouch)
  • Duodenal, colorectal, or pouch polyp: >2 centimeter (cm) unless excised at the screening evaluation; and 1 to 2 cm with evidence of high-grade dysplasia upon biopsy unless excised
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE France,   Germany,   Israel,   Netherlands,   Poland,   Puerto Rico,   Spain,   Sweden,   United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT03649971
Other Study ID Numbers  ICMJE CR108515
CNTO1959COR1001 ( Other Identifier: Janssen Research & Development, LLC )
2019-001980-57 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP