LY3471851 for Ulcerative Colitis

(INSTRUCT-UC Trial)

No longer recruiting at 192 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nektar Therapeutics

Must not be taking: Cyclosporine, Tacrolimus, Mycophenolate, Thalidomide

Disqualifiers: Crohn's disease, Abdominal surgery, Cancer, others

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

Compensation: Varies

Number of Visits: 27

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if a new drug, LY3471851, is safe and effective for adults with moderate to severe ulcerative colitis (UC), a chronic condition causing colon inflammation. Participants will receive either a high dose, a low dose of the drug, or a placebo (a harmless, inactive substance) through injections over 52 weeks. Suitable candidates include those whose UC has not responded well to other treatments, such as corticosteroids or advanced therapies, and who have experienced symptoms for at least three months. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important advancements in UC treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain treatments like cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 2 weeks before screening.

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

Research has shown that LY3471851 has been tested in people with conditions like eczema and lupus. In these studies, most participants responded well to the treatment. Some mild side effects occurred, but nothing serious or unexpected.

In studies involving patients with skin issues like atopic dermatitis and psoriasis, LY3471851 was generally well-tolerated, with most people not experiencing severe side effects.

LY3471851 is currently undergoing a Phase 2 trial for ulcerative colitis, so researchers continue to gather information about its safety for this condition. However, its testing in other conditions provides some reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Researchers are excited about LY3471851 for ulcerative colitis because it works differently from many current treatments like corticosteroids, immunosuppressants, and biologics. LY3471851 is designed for targeted action, potentially offering a new mechanism of action that directly addresses inflammation in a novel way. Furthermore, it is administered as a subcutaneous injection every two weeks, which may offer a more convenient dosing schedule compared to some existing therapies. This targeted approach and simpler administration might lead to better outcomes and quality of life for patients.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research has shown that LY3471851 yields promising results for treating conditions like psoriasis and atopic dermatitis. LY3471851 boosts certain cells that help control the immune system and reduce inflammation. In individuals with psoriasis, it has been safe and improved their skin condition. This trial will study different doses of LY3471851, with some participants receiving a high dose and others a low dose, to evaluate its potential in treating ulcerative colitis by reducing gut inflammation. Although more research is needed, these early findings offer hope for its potential in treating ulcerative colitis. ^{2 3 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Nektar Therapeutics

Are You a Good Fit for This Trial?

Inclusion Criteria

Have moderately to severely active ulcerative colitis (UC) as defined by a modified Mayo score (MMS) of 4 to 9 with an endoscopic subscore (ES) ≥2, with endoscopy performed within 14 days before baseline.

Have evidence of UC extending proximal to the rectum (with ≥15 centimeters (cm) of involved colon).

Have up-to-date colorectal cancer surveillance performed according to local standard.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous injections of LY3471851 or placebo every 2 weeks from weeks 0 to 12. Responders continue treatment, while non-responders enter an extension period.

12 weeks

6 visits (in-person)

Extension

Non-responders receive high dose LY3471851 every 2 weeks up to week 50. Responders continue with the same treatment.

38 weeks

19 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• LY3471851
• Placebo

How Is the Trial Designed?

Group I: Low dose LY3471851 Experimental Treatment 1 Intervention

Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.

Group II: High dose LY3471851 Experimental Treatment 1 Intervention

Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.

Group III: Placebo Placebo Group 2 Interventions

Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.

Who Is Running the Clinical Trial?

Nektar Therapeutics

Lead Sponsor

Trials

59

Recruited

9,900+

Howard W. Robin

Nektar Therapeutics

Chief Executive Officer since 2007

B.S. in Accounting and Finance from Fairleigh Dickinson University

Dr. Dimitry Nuyten

Nektar Therapeutics

Chief Medical Officer since 2022

MD

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

The study systematically analyzed placebo effects from randomized, placebo-controlled trials, revealing that while placebos can influence clinical symptoms, they do not affect laboratory values like blood glucose in diabetics.

Placebo side effects were found to be similar to those of active treatments, highlighting the importance of careful placebo use in clinical research to ensure patient safety and informed consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. Weihrauch, TR.[2019]

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

Adverse events (AEs) are reported in 49.1% of trial participants in placebo groups, indicating that these events are quite common and not solely due to the natural progression of conditions.

The prevalence of AEs in placebo groups (6.51%) is higher than in untreated groups (4.25%), suggesting that the nocebo effect may play a significant role in the experience of AEs during clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Howick, J., Webster, R., Kirby, N., et al.[2022]

Citations

1. ir.nektar.com ir.nektar.com/news-releases/news-release-details/nektar-therapeutics-presents-data-rezpegaldesleukin-ly3471851

Nektar Therapeutics Presents Data for Rezpegaldesleukin ... Nektar Therapeutics Presents Data for Rezpegaldesleukin (LY3471851) in Patients with Atopic Dermatitis and Psoriasis from Two Separate Clinical ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04433585

A Study of LY3471851 in Adults With Systemic Lupus ... The reason for this study is to see if the study drug LY3471851 (NKTR-358) is safe and effective in adults with systemic lupus erythematosus (SLE). Detailed ...

3. trial.medpath.com trial.medpath.com/clinical-trial/bb04f6045a01af8a/nct04119557-safety-tolerability-pharmacokinetics-ly3471851-psoriasis

A Study of LY3471851 in Participants With Psoriasis - MedPath Participants received 24 μg/kg of LY3471851 SC every 2 weeks for a period of 12 weeks. Primary Outcome Measures. Name, Time ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04081350

NCT04081350 | A Study of LY3471851 in Participants With ... The main purpose of this study is to learn more about the safety and side effects of LY3471851 when given by injection just under the skin to participants with ...

5. s3.eu-central-1.amazonaws.com s3.eu-central-1.amazonaws.com/cst.eadv/eadv2022/29808.html.pdf

Efficacy and Safety of a Selective Regulatory T-Cell ... The IL-2 conjugate Treg stimulator, LY3471851, showed a consistent safety profile in patients with PsO as previously seen. In pts treated with LY3471851 Treg ...

6. abmole.com abmole.com/literature/ly3471851-msds.html?srsltid=AfmBOopoy2OBXkKUfP7nxak2a1pqa0jRQy5cWMk8gk-I6tdABW6YvN4y

Material Safety Data Sheet of LY3471851 Material Safety Data Sheet of LY3471851 contains identification of substance and details of the supplier of the safety data sheet.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03556007

NCT03556007 | A Study of NKTR-358 (LY3471851) in ... The main purpose of this study is to evaluate the safety and tolerability of a study drug known as LY3471851 in participants with SLE. The study will last about ...

8. prnewswire.com prnewswire.com/news-releases/nektar-therapeutics-presents-data-for-rezpegaldesleukin-ly3471851-in-patients-with-atopic-dermatitis-and-psoriasis-from-two-separate-clinical-studies-at-2022-european-academy-of-dermatology-eadv-congress-301618829.html

Nektar Therapeutics Presents Data for Rezpegaldesleukin ... In patients treated with LY3471851: Treg numbers increased; PASI, sPGA scores, and Itch NRS improved over the treatment period; PASI improvement ...