E0348 - Health-Related Quality of Life of Week 8 Responders and Non-Responders: Results from the RBX2660 Phase 3 Randomized, Placebo-Controlled Trial in Recurrent Clostridioides difficile Infection (PUNCH CD3)

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

AG

Amy Guo, PhD

Ferring Pharmaceuticals
Parsippany, NJ

Paul Feuerstadt, MD, FACG¹, Erik R. Dubberke, MD, MSPH², Amy Guo, PhD³, Adam Harvey, PhD⁴, Min Yang, MD, PhD, MS⁵, Viviana Garcia-Horton, PhD⁶, Mirko Fillbrunn, PhD⁵, Jonathan Salcedo, PhD⁵, Glenn Tillotson, PhD⁷, Lindy Bancke, PharmD⁴, Kevin W. Garey, PharmD, MS, FASHP, FIDSA, FCCP⁸
¹PACT Gastroenterology Center and Yale University School of Medicine, New Haven, CT; ²Washington University School of Medicine, St. Louis, MO; ³Ferring Pharmaceuticals, Parsippany, NJ; ⁴Rebiotix Inc., a Ferring Company, Roseville, MN; ⁵Analysis Group, Inc., Boston, MA; ⁶Analysis Group, Inc., New York, NY; ⁷GST Micro, North, VA; ⁸University of Houston College of Pharmacy, Houston, TX

Introduction: Recurrent Clostridioides difficile infection (rCDI) substantially compromises patients’ health-related quality of life (HRQL). RBX2660, a live biotherapeutic product (LBP), was found to reduce rCDI. Here we report post-hoc HRQL results of responders (with no recurrence) and non-responders (with a recurrence) within an 8-week blinded period of the RBX2660 phase 3 randomized placebo-controlled trial PUNCH CD3 (NCT03244644).

Methods: We analyzed the Clostridioides difficile Health-related Quality-of-Life Questionnaire (Cdiff32), a validated disease-specific instrument with three domains (physical, mental, and social) and a total score (all range from 0–100, 100 best possible). Changes in Cdiff32 from baseline to week 8 were summarized for responders and non-responders, respectively, for RBX2660 and placebo (PBO). Per trial protocol, patients experiencing recurrence after blinded treatment received open-label RBX2660 per physician discretion; these participants were excluded. Adjusted regressions were conducted among responders only due to low sample size of non-responders, and controlling for baseline score, age, sex, number of prior CDI episodes, and other covariates. As-observed data were used.

Results: Among patients with available Cdiff32 at baseline and week 8, 178 patients (125 RBX2660, 53 PBO) were responders and 7 (3 RBX2660, 4 PBO) were non-responders. Responders were aged (mean±SD) 59.3±16.7 yrs, 68.5% female; non-responders were aged 66.4±16.4 yrs, 85.7% female. Among responders, improvements from baseline to week 8 were statistically significant (all p< 0.001) for both arms and all Cdiff32 scores (Table 1). Adjusted analyses among responders found a statistical difference favoring RBX2660 vs PBO at week 8 for the mental domain (7.4, 95% confidence interval: [0.33, 14.43], P< 0.05). Among non-responders, numerical improvements in all four scores were observed for RBX2660, while scores remained similar from baseline to week 8 for PBO.

Discussion: HRQL of rCDI patients treated with RBX2660 and with standard antibiotic treatment (PBO) improved significantly among the responders, with a greater magnitude for RBX2660, particularly for mental health. Among the few non-responders, an average improvement in 10 to 20 points on Cdiff32 was observed for RBX2660-treated patients though not among PBO-treated patients. These findings suggest future research is warranted to further evaluate the potential impact of LBP on HRQL of patients with rCDI.

	RBX2660				Placebo
Component (Mean ± SD)	Baseline	Week 8	Change from baseline	Unadjusted P-value	Baseline	Week 8	Change from baseline	Unadjusted P-value
Responders
Total	43.7 ± 17.4	75.8 ± 18.3	32.1 ± 21.4	< 0.001 *	42.4 ± 20.3	70.1 ± 23.2	27.7 ± 19.8	< 0.001 *
Physical	52.6 ± 21.1	84.2 ± 16.9	31.7 ± 22.8	< 0.001 *	49.9 ± 22.7	79.2 ± 21.6	29.3 ± 23.2	< 0.001 *
Mental	32.7 ± 16.8	66.4 ± 22.0	33.7 ± 24.1	< 0.001 *	33.0 ± 20.5	60.1 ± 27.0	27.0 ± 21.4	< 0.001 *
Social	53.5 ± 23.6	80.2 ± 21.3	26.6 ± 27.9	< 0.001 *	49.3 ± 26.5	73.6 ± 27.8	24.3 ± 27.3	< 0.001 *
Non-responders
Total	61.5 ± 16.7	76.3 ± 5.9	14.8 ± 16.4	0.423	59.0 ± 31.0	57.2 ± 35.0	-1.8 ± 25.6	0.854
Physical	78.0 ± 14.9	91.1 ± 4.7	13.1 ± 19.3	0.423	62.5 ± 35.3	62.1 ± 37.8	-0.5 ± 30.8	0.855
Mental	47.0 ± 19.6	60.7 ± 15.6	13.7 ± 16.2	0.181	54.9 ± 27.7	50.0 ± 33.2	-4.9 ± 23.3	0.854
Social	54.2 ± 15.7	79.2 ± 3.6	25.0 ± 16.5	0.181	60.9 ± 33.2	65.6 ± 34.8	4.7 ± 22.5	1.000

Table: Cdiff32 component scores at baseline and week 8 by treatment arm and response status.

Disclosures:

Paul Feuerstadt: Ferring/Rebiotix Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau. Merck and Co – Consultant. Seres Therapeutics – Advisory Committee/Board Member, Consultant. Takeda Pharmaceuticals – Advisory Committee/Board Member.

Erik R. Dubberke: Abbott – Consultant. Ferring Pharmaceuticals – Consultant, Grant/Research Support. Merck – Consultant. Pfizer – Consultant, Grant/Research Support. Rebiotix – Advisory Committee/Board Member. Seres – Consultant. Summit – Consultant. Synthetic Biologics – Grant/Research Support.

Amy Guo: Ferring Pharmaceuticals – Employee.

Adam Harvey: Rebiotix Inc., a Ferring Company – Employee.

Min Yang: Analysis Group, Inc. – Employee, Analysis Group has received consulting fees from Ferring Pharmaceuticals.

Viviana Garcia-Horton: Analysis Group, Inc. – Employee, Analysis Group has received consulting fees from Ferring Pharmaceuticals.

Mirko Fillbrunn: Analysis Group, Inc. – Employee, Analysis Group has received consulting fees from Ferring Pharmaceuticals.

Jonathan Salcedo: Analysis Group, Inc. – Employee, Analysis Group has received consulting fees from Ferring Pharmaceuticals.

Glenn Tillotson: Ferring Pharmaceuticals – Consultant. GST Micro LLC – Employee. Spero Pharmaceuticals – Consultant. Taro Pharmaceuticals – Consultant.

Lindy Bancke: Rebiotix Inc., a Ferring company – Employee.

Kevin W. Garey: Acurx – Grant/Research Support. Ferring Pharmaceuticals – Consultant. Paratek Pharmaceuticals – Grant/Research Support. Seres Health – Grant/Research Support. Summit – Grant/Research Support.