RO7790121 for Crohn's Disease

(SIBERITE-2 Trial)

Recruiting at 149 trial locations

Overseen By Reference Study ID Number: GA45332 https://forpatients.roche.com/

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Anti-TL1A therapy

Disqualifiers: Ulcerative colitis, Short bowel, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

425 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness and safety of a new treatment called Afimkibart (also known as RO7790121) for people with Crohn's disease, a condition that causes inflammation in the digestive tract. Participants will receive either Afimkibart or a placebo (a substance with no active drug) to compare results. The trial seeks individuals with moderate to severe Crohn's disease who have not responded well to other treatments. The study aims to find a new option for those struggling with Crohn's disease symptoms. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain medicines are prohibited, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that RO7790121 is likely to be safe for humans?

Research has shown that Afimkibart (RO7790121) has been tested in people with moderately to severely active Crohn's disease. In these studies, most patients tolerated Afimkibart well. Some experienced side effects, usually mild, such as headaches and nausea, while serious side effects were rare.

Since this treatment is in a Phase 3 trial, it has already passed earlier safety tests. These earlier phases demonstrated it was safe enough for broader testing, which is a positive indicator for its safety in humans. However, like any treatment, risks exist, and it is important to consider them before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Crohn's disease?

Researchers are excited about afimkibart for Crohn's Disease because it offers a new approach to treatment. Most current treatments, like biologics and immunosuppressants, work by broadly dampening the immune system. However, afimkibart specifically targets pathways involved in the inflammation process, potentially reducing side effects and improving effectiveness. Additionally, its dual delivery method, starting with an intravenous (IV) dose followed by a subcutaneous (SC) injection, may enhance its absorption and convenience for patients. This targeted approach and delivery method set afimkibart apart from traditional therapies.

What evidence suggests that RO7790121 might be an effective treatment for Crohn's disease?

Research has shown that Afimkibart, also known as RO7790121, may help treat moderate to severe Crohn's disease. In this trial, participants will receive either Afimkibart or a placebo. Studies have found that patients taking Afimkibart experienced significant symptom improvements. Specifically, one study revealed that almost half of the patients noticed benefits during the early treatment stage, and more than half continued to improve later on. These results suggest that Afimkibart could be a helpful option for managing Crohn's disease symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with Crohn's Disease who haven't responded well to other treatments. They must weigh at least 40 kg and follow specific contraception rules if they can have children. People can't join if they're pregnant, breastfeeding, planning pregnancy, have certain types of fistulas or bowel issues, a history of some infections or cancers within the last five years, or have used prohibited medications.

Inclusion Criteria

I have been diagnosed with Crohn's disease.

My Crohn's disease is moderate to severe.

I am following the required birth control measures.

Exclusion Criteria

Pregnancy or breastfeeding, or intention of becoming pregnant during the study

I have a fistula with more than 3 openings.

I have an ileostomy, colostomy, or ileoanal pouch.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive induction therapy with RO7790121 or placebo intravenously, followed by subcutaneous injections

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RO7790121

Trial Overview The study tests RO7790121 against a placebo in people with moderate to severe Crohn's Disease. It's a Phase III trial where participants are randomly assigned to receive either the experimental drug or an inactive substance without knowing which one they get (double-blind).

How Is the Trial Designed?

Group I: Afimkibart Experimental Treatment 1 Intervention

Participants will receive afimkibart intravenously (IV) followed by afimkibart subcutaneous (SC) injection.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo IV followed by afimkibart SC injection.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Chugai Pharmaceutical

Industry Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Published Research Related to This Trial

Infliximab treatment led to a rapid remission in 88% of patients with steroid-refractory Crohn's disease after just one week, but the long-term effectiveness decreased significantly over time, with only 8% remaining in remission by 16 weeks.

Patients who relapsed after initial remission showed increased TNF-alpha secretion and elevated levels of nuclear NFkappaB p65 in their mucosal biopsies, indicating that these immune markers may predict clinical relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms in failure of infliximab for Crohn's disease. Nikolaus, S., Raedler, A., Kühbacker, T., et al.[2019]

Risankizumab was evaluated as an induction therapy for Crohn's disease in two phase 3 trials (ADVANCE and MOTIVATE), demonstrating significant efficacy in achieving clinical remission among participants.

The results indicated that risankizumab effectively reduced disease activity in patients with Crohn's disease, suggesting it could be a promising treatment option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In active Crohn disease, risankizumab increased clinical remission and endoscopic response at 12 wk. Oliver, D., Talley, NJ.[2022]

In a 52-week study involving 24 patients with Crohn's disease who previously lost response to infliximab, adalimumab demonstrated significant efficacy, with clinical remission rates increasing from 35% at baseline to 58% at week 52.

Adalimumab was well tolerated, with no patients experiencing intolerance and no serious toxicities reported, indicating it is a safe option for maintaining remission in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. Peyrin-Biroulet, L., Laclotte, C., Bigard, MA.[2015]

In a phase 2 trial involving 220 adults with moderate to severe Crohn's disease, upadacitinib demonstrated significant efficacy in inducing endoscopic remission, particularly at the 24 mg dose, compared to placebo.

While upadacitinib showed promising results, it was associated with higher rates of infections and increased cholesterol levels, indicating a need to carefully consider its safety profile in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn's Disease. Sandborn, WJ., Feagan, BG., Loftus, EV., et al.[2021]

In a study of 6,273 Crohn's disease patients with an average follow-up of 5.2 years, infliximab treatment did not increase mortality risk compared to other treatments, indicating its long-term safety in this regard.

However, infliximab was associated with a higher risk of serious infections, although this risk was also influenced by the severity of the disease and the use of medications like prednisone and narcotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry. Lichtenstein, GR., Feagan, BG., Cohen, RD., et al.[2022]

In a long-term study of 107 patients with Crohn's disease, upadacitinib demonstrated sustained clinical remission rates of around 54-61% over 30 months, indicating its efficacy as a treatment.

While upadacitinib showed long-term benefits, the safety profile revealed that higher doses (30 mg) were associated with increased rates of adverse events compared to lower doses (15 mg), consistent with its known safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Was Efficacious and Well-tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study. D'Haens, G., Panés, J., Louis, E., et al.[2022]

In a study of 221 Crohn's disease patients treated with ustekinumab over a median follow-up of 52 weeks, 38.2% achieved corticosteroid-free clinical remission by week 24, and 37.1% by week 52, indicating its effectiveness in managing the disease.

Ustekinumab was found to be relatively safe, with a low incidence of severe infections (3.5 per 100 patient-years), and treatment discontinuation primarily occurred due to lack of response, affecting 33.9% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab for Crohn's Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study. Biemans, VBC., van der Meulen-de Jong, AE., van der Woude, CJ., et al.[2020]

Nayar et al. identified specific inflammatory cell populations that play a role in the development of Crohn's disease (CD), highlighting the importance of understanding these cells in disease management.

The study suggests that targeting the gp130-STAT3 signaling pathway could be a promising new treatment strategy for patients with CD who do not respond to anti-TNF antibody therapies, potentially enhancing existing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

gp130 blockade to NOD off Crohn's disease. Mukherjee, T., Philpott, DJ.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06819878

NCT06819878 | A Study to Assess the Efficacy and Safety ... A Study to Assess the Efficacy and Safety of Induction and Maintenance Therapy With Afimkibart (RO7790121) in Participants With Moderately to Severely Active ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40706613/

Anti-TL1A antibody, afimkibart, in moderately-to-severely ... However, secondary endpoints suggest that afimkibart was associated with a favourable benefit-risk profile, with clinically meaningful ...

3. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/autoimmune-disorder/crohn-s-disease/a-study-to-assess-the-efficacy-and-safety-of-induction--94939.html

Clinical Study | Crohn's Disease RO7790121 | ForPatients-... A study to assess the effectiveness and safety of induction therapy with RO7790121 in participants with moderately to severely active Crohn's disease.

4. forpatients.roche.com forpatients.roche.com/content/patient-platform/global/en/trials/autoimmune-disorder/crohn-s-disease/a-study-to-assess-the-efficacy-and-safety-of-induction--32899.pdf

A study to test the effectiveness and safety of RO7790121 for ... This Phase III, multicenter, double-blind, placebo-controlled treat-through study will evaluate the efficacy and safety of induction and maintenance therapy ...

5. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(25)00129-3/abstract

Anti-TL1A antibody, afimkibart, in moderately-to-severely ... Overall, 117 (48%) of 245 patients in the induction phase and 132 (59%) of 224 patients in the maintenance phase reported at least one treatment ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05910528

Study Details | NCT05910528 | Afimkibart (RO7790121) for ... This Phase 2, randomized, double-blind, multicenter, induction and maintenance study is designed to evaluate the safety and efficacy of Afimkibart (RO7790121, ...

7. mayo.edu mayo.edu/research/clinical-trials/cls-20588363

Clinical Trials A Study To Assess The Efficacy And Safety Of Induction And Maintenance Therapy With Afimkibart (RO7790121) In Participants With Moderately To ...