A Study of LY3471851 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC)

(INSTRUCT-UC Trial)

Recruiting at 154 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

81 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine called LY3471851 to see if it is safe and effective for adults with active ulcerative colitis. The medicine aims to help by boosting immune cells that reduce inflammation in the colon.

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 the treatment generally safe for humans?

In studies where people were given a placebo (a dummy treatment with no active drug), some reported side effects like headaches, feeling sleepy, and weakness. This suggests that even treatments without active ingredients can cause these effects, so it's important to consider that similar side effects might occur with the treatment being studied. ^{1 2 3 4 5}

Research Team

Study Director

Principal Investigator

Nektar Therapeutics

Eligibility Criteria

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

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)

Treatment Details

Interventions

• LY3471851
• Placebo

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Does maintained spinal manipulation therapy for chronic nonspecific low back pain result in better long-term outcome? [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Combined magnetic fields accelerate and increase spine fusion: a double-blind, randomized, placebo controlled study. [2019]