A Study of Guselkumab in Participants With Familial Adenomatous Polyposis
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| ClinicalTrials.gov Identifier: NCT03649971 |
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Recruitment Status :
Recruiting
First Posted : August 28, 2018
Last Update Posted : December 30, 2020
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Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adenomatous Polyposis Coli | Drug: Guselkumab Drug: Placebo | Phase 1 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 72 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1b, Multicenter, Randomized, Blinded, Placebo-controlled Study to Evaluate the Efficacy of Guselkumab in Subjects With Familial Adenomatous Polyposis |
| Actual Study Start Date : | November 19, 2018 |
| Estimated Primary Completion Date : | July 30, 2021 |
| Estimated Study Completion Date : | March 28, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Familial adenomatous polyposis
Drug Information available for:
Guselkumab
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Guselkumab
Guselkumab SC will be administered every 4 weeks.
Other Name: Tremfya |
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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.
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Drug: Guselkumab
Guselkumab SC will be administered every 4 weeks.
Other Name: Tremfya |
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Placebo Comparator: Placebo
Participants will receive placebo SC, 6 doses every 4 weeks from Week 0 to Week 20.
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Drug: Placebo
Placebo SC will be administered every 4 weeks. |
Primary Outcome Measures :
- 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 Outcome Measures :
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03649971
Contacts
| Contact: Study Contact | 844-434-4210 | JNJ.CT@sylogent.com |
Locations
Show 34 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Additional Information:
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT03649971 |
| Other Study ID Numbers: |
CR108515 CNTO1959COR1001 ( Other Identifier: Janssen Research & Development, LLC ) 2019-001980-57 ( EudraCT Number ) |
| First Posted: | August 28, 2018 Key Record Dates |
| Last Update Posted: | December 30, 2020 |
| Last Verified: | December 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Colorectal Neoplasms Nasopharyngeal Neoplasms Adenomatous Polyposis Coli Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Pharyngeal Neoplasms |
Otorhinolaryngologic Neoplasms Head and Neck Neoplasms Nasopharyngeal Diseases Pharyngeal Diseases Stomatognathic Diseases Otorhinolaryngologic Diseases Adenomatous Polyps Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplastic Syndromes, Hereditary Intestinal Polyposis Genetic Diseases, Inborn |