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Adenomatous Polyposis ColiPhase 1NCT03649971

A Study of Guselkumab in Participants With Familial Adenomatous Polyposis

A Phase 1 study testing Guselkumab in people with Adenomatous Polyposis Coli, run by Janssen Research & Development, LLC at 32 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Adenomatous Polyposis Coli
What is being tested?
Guselkumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
77 participants
Where
32 sitesin 9 countries
Study dates
19 Nov 2018to 23 Mar 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

32 sites in 9 countries.

32 sites in 9 countries

United States18 sites
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Wexner Medical Center at the Ohio State University

    Columbus, Ohio, 43210

  • City of Hope

    Duarte, California, 91010

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • University of Miami

    Miami, Florida, 33136

  • Yale University

    New Haven, Connecticut, 06519

  • Ochsner Medical Center

    New Orleans, Louisiana, 70121

  • Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

    New York, New York, 10032

  • University of Pennsylvania - Perelman School of Medicine

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • University of Utah Huntsman Cancer Institute

    Salt Lake City, Utah, 84132

  • University of Washington

    Seattle, Washington, 98195

  • Washington University School Of Medicine

    St Louis, Missouri, 63110

  • University of South Florida

    Tampa, Florida, 33606

Other trials in United States

Netherlands3 sites
  • Academisch Medisch Centrum Universiteit van Amsterdam

    Amsterdam, 1105 AZ

  • Leiden University Medical Center

    Leiden, 2333 ZA

  • Erasmus MC

    Rotterdam, 3015 GD

Other trials in Netherlands

France2 sites
  • Hopital Edouard Herriot - CHU Lyon

    Lyon, 69437

  • APHM Hopital Timone

    Marseille, 13385

Other trials in France

Germany2 sites
  • Universitatsklinikum Bonn

    Bonn, 53127

  • Universitatsklinikum Ulm

    Ulm, 89070

Other trials in Germany

Poland2 sites
  • Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Po

    Poznan, 60 355

  • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

    Warsaw, 02-781

Other trials in Poland

Spain2 sites
  • Hosp Univ Vall D Hebron

    Barcelona, 8035

  • Hosp Clinic de Barcelona

    Barcelona, 8036

Other trials in Spain

Israel1 site
  • Sourasky MC

    Tel Aviv, 64239

Other trials in Israel

Puerto Rico1 site
  • Pan American Center for Oncology Trials LLC

    Rio Piedras, 00935

Other trials in Puerto Rico

Sweden1 site
  • Karolinska Universitetssjukhuset

    Stockholm, 171 76

Other trials in Sweden

About this study

Official title: A Phase 1b, Multicenter, Randomized, Blinded, Placebo-controlled Study to Evaluate the Efficacy of Guselkumab in Subjects With Familial Adenomatous Polyposis

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.

Read the 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).

Being tested
Guselkumab, Placebo
Medical subject headings
Adenomatous Polyposis Coli

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GuselkumabDrug

    Also called Tremfya

    Guselkumab SC will be administered every 4 weeks.

  • PlaceboDrug

    Placebo SC will be administered every 4 weeks.

Study groups in NCT03649971
Study groupRoleWhat they receive
Guselkumab Dose 1ExperimentalParticipants 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.
Receives: Drug: Guselkumab
Guselkumab Dose 2ExperimentalParticipants 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.
Receives: Drug: Guselkumab
PlaceboPlacebo comparatorParticipants will receive placebo SC, 6 doses every 4 weeks from Week 0 to Week 20.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage Change from Baseline in Rectal/pouch Polyp Burden at Week 24

    Percentage change from baseline in rectal/pouch polyp burden (sum of the polyp diameters) at Week 24 will be determined through endoscopy.

    Measured: Baseline, Week 24

Secondary outcomes (14)
  1. Percentage Change from Baseline in Number of Colorectal Polyps

    Percentage change from baseline in number of colorectal polyps will be determined.

    Measured: Baseline, Weeks 24 and 52

  2. Percentage Change from Baseline in Number of J-pouch Polyps

    Percentage change from baseline in number of J-pouch polyps will be determined.

    Measured: Baseline, Weeks 24 and 52

  3. Percentage Change from Baseline in J-pouch Polyp Burden

    Percentage change from baseline in J-pouch polyp burden (sum of polyp diameters) will be determined.

    Measured: Baseline, Weeks 24 and 52

  4. Percentage Change from Baseline in Number of Duodenal Polyps

    Percentage change from baseline in number of duodenal polyps will be determined.

    Measured: Baseline, Weeks 24 and 52

  5. Percentage Change from Baseline in Duodenal Polyp Burden

    Percentage change from baseline in duodenal polyp burden (sum of polyp diameters) will be determined.

    Measured: Baseline, Weeks 24 and 52

  6. Change in International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Stage

    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).

    Measured: Baseline, Weeks 24 and 52

  7. Change in Spigelman Stage Score

    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.

    Measured: Baseline, Weeks 24 and 52

  8. Trough Concentration of Guselkumab

    Serum samples will be analyzed to determine trough concentrations of guselkumab using a validated specific, and sensitive method.

    Measured: Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48

  9. Number of Participants with Anti-guselkumab Antibodies

    Number of participants with Anti-guselkumab antibodies will be determined.

    Measured: Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48

  10. Anti-guselkumab Antibodies Serum Titers

    Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed positive samples will be reported.

    Measured: Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, and 48

  11. Number of Participants with Adverse Events as a Measure of Safety

    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.

    Measured: From Screening up to 60 Weeks

  12. Number of Participants with Vital Sign Abnormalities as a Measure of Safety and Tolerability

    Number of participants with vital sign abnormalities will be reported. Vital signs includes temperature, pulse/heart rate, respiratory rate and blood pressure.

    Measured: From Screening up to 52 Weeks

  13. Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability

    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.

    Measured: From Screening up to 52 Weeks

  14. Relative Changes to Baseline in Levels of Interleukin (IL)-23 Effector Proteins in Biopsy Tissue

    Relative Changes to Baseline in levels of IL-23 effector proteins in biopsy tissue will be measured.

    Measured: Baseline, Weeks 12, 24, and 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2018
  2. Study start19 Nov 2018
  3. Primary completion13 Sep 2021
  4. Study completion23 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03649971
Sponsor's protocol ID
CR108515
Other IDs
CNTO1959COR1001, 2019-001980-57, 2019
Status last verified
Jan 2025
First submitted
27 Aug 2018
Last updated
3 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Stone JK, Mehta NA, Singh H, El-Matary W, Bernstein CN. Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome. Fam Cancer. 2023 Oct;22(4):413-422. doi: 10.1007/s10689-023-00334-3. Epub 2023 Apr 29.

    PubMed 37119510

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Guselkumab in people with Adenomatous Polyposis Coli, run by Janssen Research & Development, LLC at 32 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, Netherlands, France, Germany, Poland and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage Change from Baseline in Rectal/pouch Polyp Burden at Week 24 (time frame: Baseline, Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03649971, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.

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