Oral Etrasimod for Crohn's Disease

(CULTIVATE Trial)

No longer recruiting at 1121 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Disqualifiers: Ulcerative colitis, Short-bowel syndrome, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called etrasimod for individuals with Crohn's disease, a condition that inflames the digestive tract. The trial aims to assess the effectiveness and safety of etrasimod for those who have not responded well to treatments like steroids or biologics. Participants will receive either one of two doses of etrasimod or a placebo (a pill with no active medicine) to compare results. This trial suits individuals diagnosed with Crohn's disease for at least three months who experience moderate to severe symptoms despite trying other treatments. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new 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. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that etrasimod has been safe in past studies. In studies involving patients with ulcerative colitis, etrasimod was generally well-tolerated. Most side effects were mild to moderate, with common ones including headaches and some changes in lab tests, but these were not serious.

Another study found that etrasimod was safe and effective compared to a placebo, indicating that patients taking etrasimod did not experience more serious side effects than those taking a non-active pill.

While these results are encouraging, they are based on conditions similar to, but not exactly like, Crohn’s disease. The current study for Crohn's disease will provide more specific safety information for this group. ^{1 2 3 4 5}

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

Unlike the standard treatments for Crohn's Disease, which often include anti-inflammatory drugs like corticosteroids and immunosuppressants, Etrasimod offers a novel approach by targeting the S1P receptor. This unique mechanism helps modulate the immune system to reduce inflammation more precisely. Researchers are excited about Etrasimod because it promises fewer side effects and potentially more effective symptom control. Plus, it’s an oral medication, making it more convenient than some current treatments that require injections or infusions.

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

Research has shown that etrasimod may help treat conditions like Crohn's disease. In earlier studies, 64% of patients were symptom-free by week 12, though this number decreased to 18% by week 26. Another study found that by week 52, 44% of patients were symptom-free. Etrasimod has also effectively maintained symptom relief without steroids. In this trial, participants will receive either etrasimod or a placebo. Previous studies have consistently shown that etrasimod improves symptoms more effectively than a placebo. ^{1 3 4 5 6}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Adults aged 18-80 with moderate to severe Crohn's Disease, who haven't responded well to or can't tolerate steroids, immunosuppressants, or biologics. They must be able to follow the study plan and use contraception if they can have children.

Inclusion Criteria

My Crohn's disease is currently moderate to severe.

I have Crohn's disease and treatments like steroids, immunosuppressants, or biologics didn’t work for me.

I have been diagnosed with Crohn's disease for at least 3 months.

Exclusion Criteria

You have a surgical opening in your abdomen to help eliminate waste.

I have short-bowel syndrome that might need surgery or affect treatment results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive etrasimod as induction therapy to evaluate efficacy and select doses for maintenance

24 weeks

Maintenance

Participants continue to receive etrasimod to evaluate long-term efficacy and safety

42 weeks

Long-Term Extension

Participants who complete at least 52 weeks of treatment may continue in a long-term extension to further assess safety and efficacy

212 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Etrasimod
• Placebo

Trial Overview The trial is testing Etrasimod, an oral medication for Crohn's Disease. It compares Etrasimod against a placebo over several years to check its effectiveness and safety in those not helped by standard treatments.

How Is the Trial Designed?

Group I: Etrasimod Dose B Experimental Treatment 1 Intervention

Group II: Etrasimod Dose A Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Arena Pharmaceuticals

Lead Sponsor

Trials

29

Recruited

5,800+

Arena is a wholly owned subsidiary of Pfizer

Collaborator

Trials

7

Recruited

2,500+

Arena is a wholly owned subsidiary of Pfizer

Industry Sponsor

Trials

11

Recruited

2,600+

Published Research Related to This Trial

In a study involving 180 patients with active moderate-severe Crohn's disease, laquinimod at a dose of 0.5 mg/day was found to be effective, achieving remission in 48.3% of patients compared to 15.9% in the placebo group.

Laquinimod was safe and well tolerated, with adverse events occurring at similar rates to placebo, indicating that it may be a promising treatment option for Crohn's disease, particularly at the lower dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of laquinimod in Crohn's disease. D'Haens, G., Sandborn, WJ., Colombel, JF., et al.[2021]

Corticosteroids are the most effective treatment for active Crohn's disease, achieving remission in 65-85% of patients, significantly outperforming other older drugs like high-dose sulphasalazine and 5-aminosalicylic acid.

For patients with steroid-refractory Crohn's disease, immunosuppressives like azathioprine and 6-mercaptopurine offer a 'steroid-sparing' effect and can help with fistula closure, although they are less effective than steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment modalities in active Crohn's disease. Biancone, L., Pallone, F.[2005]

The new controlled-release formulation of budesonide, Entocort CR-Astra, is designed specifically for treating Crohn's disease in the ileum and ascending colon, providing targeted therapy with rapid results similar to prednisolone.

Budesonide has a much lower systemic availability compared to prednisolone, which may lead to fewer systemic steroid side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled-release budesonide in Crohn's disease. [2019]

Budesonide is an effective treatment for mild to moderately active right-sided Crohn's disease, showing superiority over mesalamine and placebo, and comparable efficacy to prednisolone, while causing less adrenal suppression.

However, budesonide is not beneficial for left-sided colonic disease and is less effective for severe disease, making it best suited for intermittent use during acute flare-ups rather than continuous treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted delivery, safety, and efficacy of oral enteric-coated formulations of budesonide. Fedorak, RN., Bistritz, L.[2022]

In large clinical trials involving over 176 patients with active mild to moderate Crohn's disease, oral budesonide (9 mg/day) was significantly more effective than placebo and mesalazine in inducing remission, showing similar efficacy to prednisolone.

Budesonide was well tolerated, with adverse events occurring at rates similar to placebo and mesalazine, and significantly fewer glucocorticoid-related side effects compared to prednisolone, making it a safer option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide (Entocort EC Capsules): a review of its therapeutic use in the management of active Crohn's disease in adults. McKeage, K., Goa, KL.[2022]

Citations

1. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i1537/7968072

P0801 Real-world Effectiveness and Tolerability of Etrasimod ... At week 12, 64% had achieved clinical remission, however this dropped to 18% at week 26 in an intention-to-treat (ITT) analysis (Figure 1B).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38613425/

Results From the Phase 3 ELEVATE UC Clinical Programme Etrasimod demonstrated significant improvements versus placebo in patients with isolated proctitis, and those with more extensive disease, in most efficacy ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2444382425000938

Etrasimod: Review of the efficacy and therapeutic ... At week 52 in the ELEVATE UC 52 study, 44% and 56% of patients treated with etrasimod achieved clinical and symptomatic remission, respectively, compared to 11% ...

4. academic.oup.com academic.oup.com/ecco-jcc/article/19/3/jjae150/7764041

Etrasimod Corticosteroid-Free Efficacy, Impact of Concomitant ... Etrasimod demonstrated efficacy in inducing and maintaining remission in both subgroups. CS-free remission was achieved in the CS subgroup.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39671695

Etrasimod as a Monotherapy or With Concomitant Use of ... Conclusions: Etrasimod monotherapy showed consistent efficacy and safety vs placebo; no apparent benefit was observed with concomitant CS and/or ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04173273

NCT04173273 | A Study Evaluating the Efficacy and Safety ... This is a Phase 2/3 study that comprises 5 substudies designed to evaluate the efficacy, safety, and tolerability of oral etrasimod as therapy in adult ...