Trial Design | VELSIPITY Brand Microsite

Trial Design

Baseline
Characteristics

Eligibility Criteria

Efficacy
Endpoints

VELSIPITY was studied across 2 phase 3 trials^1,2

ELEVATE UC 52 and ELEVATE UC 12 were randomized, multicenter, double-blind, placebo-controlled trials in patients 16 to 80 years of age with moderately to severely active UC^1,2

ELEVATE UC 52 and ELEVATE UC 12 were randomized, multicenter, double-blind, placebo-controlled trials²

Co-primary endpoints: Clinical remission at week 12 (ELEVATE UC 52 and ELEVATE UC 12) and week 52 (ELEVATE UC 52)²

Primary efficacy analysis was done in patients with a baseline mMS† of 5 to 9 (ELEVATE UC 52: n=409; ELEVATE UC 12: n=334)^1,2

In ELEVATE UC 52, patients whose disease had not improved or had worsened vs baseline (per investigator judgment), could discontinue treatment and, if objective disease worsening criteria were met (having an RB subscore ≥2 or an RB subscore and an SF subscore ≥4 at 2 time points ≥7 and ≤14 days apart), enroll in the OLE. In ELEVATE UC 12, at the end of week 12, patients could enroll in the OLE. In both trials, patients who did not enroll in the OLE entered a 4-week follow-up period, with visits at week 2 and at week 4.²

Enrolled patients had a modified Mayo score (mMS) of 4 to 9 with an endoscopy score (ES) ≥2 and a rectal bleeding (RB) subscore ≥1.1

OLE=open-label extension; R=randomization; RB=rectal bleeding; SF=stool frequency.

ELEVATE UC 52 used a treat-through trial design, which may more closely reflect clinical practice than a responder re-randomization trial.^2,3

Learn about a treat-through trial design

The treat-through trial design of ELEVATE UC 52 may more accurately represent clinical practice^2,3

A treat-through trial reflects outcomes for all patients who started therapy, not just those who responded during induction³

Includes nonresponders and patients who respond late to treatment, representing real-world practice^3,4

ELEVATE UC 52 was the first and only 52-week, phase 3 treat-through trial of an oral advanced therapy§ in UC²

In the treat-through trial design for ELEVATE UC 52, patients who did not respond during the 12-week induction period were still included in the week 52 analysis, rather than being ineligible for the maintenance period as in a responder re-randomization trial³
- This design may more closely reflect clinical practice, as it allows for delayed responses in the maintenance period³

In a re-randomization trial, induction responders are re-randomized for maintenance treatment; therefore, maintenance data only reflect potential outcomes for early responders, which may inflate efficacy data^3,4

^‡Based on clinician assessment.²

^§Advanced therapies include S1P receptor modulators, biologics, and JAK inhibitors.²

Caution is advised when comparing clinical trials; head-to-head, randomized trials provide the most reliable comparative efficacy evidence.2

R=randomized; RR=re-randomized.

References:

VELSIPITY (etrasimod) Summary of Product Characteristics. Brussels, Belgium: Pfizer Europe; February 2024.

Atreya R, Neurath MF. The sphingosine-1-phosphate receptor agonist etrasimod in ulcerative colitis. Lancet. 2023;401(10383):1132-1133.

Ghosh S, Sandborn WJ, Colombel JF, et al. Interpreting registrational clinical trials of biological therapies in adults with inflammatory bowel diseases. Inflamm Bowel Dis. 2016;22(11):2711-2723.

Baseline Patient Characteristics^1-3

A majority of patients in the VELSIPITY phase 3 trials were ideally suited for first-line advanced therapy^1*

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	ELEVATE UC 52 (N=433)	ELEVATE UC 12 (N=354)
Mean age	40 years	40 years
Gender (female)	45%	41%
Modified Mayo score (mMS)
4	6%	6%
5-7 (moderate)	67%	67%
>7 (severe)	28%	27%
Biologic/JAK inhibitor (JAKi) exposure
Biologic or JAKi naive	70%	67%
Biologic or JAKi prior exposure	30%	33%
>1 biologic or JAKi exposed	14%	18%
Patients with isolated proctitis	8%	8%
Concomitant treatment for UC at baseline
Oral corticosteroids	31%	28%
Oral aminosalicylates (5-ASAs)	77%	83%

*Advanced therapies include S1P receptor modulators, biologics, and JAK inhibitors.2

†Concomitant UC therapies included stable daily doses of oral aminosalicylates and/or oral corticosteroids (≤20 mg prednisone, ≤9 mg budesonide, or equivalent steroid).¹

References:

VELSIPITY (etrasimod) Summary of Product Characteristics. Brussels, Belgium: Pfizer Europe; February 2024.

Data on file. Pfizer Inc.

Atreya R, Neurath MF. The sphingosine-1-phosphate receptor agonist etrasimod in ulcerative colitis. Lancet. 2023;401(10383):1132-1133.

Sands BE, Cheifetz AS, Nduaka CI, et al. The impact of raising the bar for clinical trials in ulcerative colitis. J Crohns Colitis. 2019;13(9):1217-1226.

Select inclusion and exclusion criteria for ELEVATE UC 52 and ELEVATE UC 12¹

Select inclusion criteria:

Patients 16 to 80 years of age with moderately to severely active ulcerative colitis (UC)* and a documented history of inadequate response, a loss of response, or an intolerance to ≥1 therapy approved for the treatment of UC^†

Patients with isolated proctitis at baseline (<10 cm rectal involvement) who met other eligibility criteria could enroll in both trials, with enrollment capped at 15% of total patients^‡

Patients were allowed to receive concomitant treatment for UC before trial screening, provided they were on:

Stable doses of oral 5-ASAs 2 weeks before

Stable doses of corticosteroids (prednisone [≤20 mg/day], budesonide [≤9 mg/day], or equivalent) 4 weeks before
- Investigators were directed to taper corticosteroids in ELEVATE UC 52 after the week 12 assessment

Select exclusion criteria:

Previous treatment with ≥3 biologics or ≥2 biologics + a JAK inhibitor

A high risk of requiring a colectomy in the next 3 months (per investigator)

A clinically relevant cardiac condition^§

A history of opportunistic infections or macular edema

Pregnancy or lactation

^*In both trials, diagnosis of moderately to severely active UC was confirmed by endoscopy with ≥10 cm rectal involvement and on the basis of an mMS of 4 to 9 with a centrally read endoscopic subscore (ES) ≥2 and a rectal bleeding (RB) subscore ≥1.¹

^†Oral 5-ASAs, corticosteroids, thiopurines, JAK inhibitors, and biologics (eg, tumor necrosis factor [TNF] blockers, anti-integrins, and anti–interleukin [IL]-12 and anti–IL-23).²

^‡Enrollment of patients with isolated proctitis was capped at 15% of total population.¹

^§A history of myocardial infarction, stroke, or second-degree or third-degree atrioventricular block.¹

5-ASA=aminosalicylate; mMS=modified Mayo score.

References:

VELSIPITY (etrasimod) Summary of Product Characteristics. Brussels, Belgium: Pfizer Europe; February 2024.

VELSIPITY met all primary and key secondary endpoints^1,2

Trial endpoints were modeled after STRIDE II treatment targets^1,3

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			ELEVATE UC 52		ELEVATE UC 12
	Endpoints	Definitions	Week 12	Week 52	Week 12
Primary endpoint	Clinical remission	SF subscore of 0 or 1 RB subscore of 0 ES ≤1 (excluding friability)
Key secondary endpoints	Endoscopic improvement	ES ≤1 (excluding friability)
	Symptomatic remission	SF subscore of 0 (or SF subscore of 1 with a ≥1-point decrease from baseline) RB subscore of 0
	Histologic-endoscopic mucosal improvement	ES ≤1 (excluding friability) Histologic remission measured by a Geboes Index score <2.0
	Corticosteroid-free clinical remission	Clinical remission at week 52 in patients who had not received corticosteroids for ≥12 weeks prior to week 52	N/A		N/A
	Sustained clinical remission	Clinical remission at week 12 and at week 52	N/A		N/A
Other prespecified secondary endpoint	Clinical response	≥2-point and a ≥30% decrease from baseline in mMS ≥1-point decrease from baseline in RB subscore or absolute RB subscore ≤1

Primary and key secondary endpoints were controlled for multiplicity via parallel gatekeeping procedures that preserved the type I error rate at 5%¹

ES=endoscopic subscore; mMS=modified Mayo score; NA=not applicable; RB=rectal bleeding; STRIDE=Selecting Therapeutic Targets in Inflammatory Bowel Disease.

References:

Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies [published correction appears in Lancet. 2023;401(10381):1000]. Lancet. 2023;401(10383): 1159-1171. Supplementary appendix available at: https://www.thelancet.com/cms/10.1016/S0140-6736(23)00061-2/attachment/cdbbc759-490f-4b2a-a3a2-93bc9918b29f/mmc1.pdf. Accessed December 18, 2023.

Turner D, Ricciuto A, Lewis A, et al; International Organization for the Study of IBD. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583.