Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)

Sponsor

Rebiotix Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03244644

Collaborator

(none)

267

Enrollment

Locations

Arms

36.1

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. Patients who have had at least one recurrence after a primary episode and have completed at least one round of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization within the last year may be eligible for the study. Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded RBX2660 enema.

Condition or Disease	Intervention/Treatment	Phase
Clostridium Difficile Infection	Drug: RBX2660 Drug: Placebo	Phase 3

Detailed Description

This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. The primary assessments for this study are (i) efficacy of RBX2660 as compared to a Placebo in preventing recurrent episodes of CDI and (ii) safety via assessment of adverse events. The primary efficacy analysis of the study will be a Bayesian hierarchical model, which formally incorporates data from a previous randomized Phase 2b study (Protocol 2014-01) of RBX2660.

Follow-up office visits occur at weeks 1-, 4- and 8 after completing the blinded study treatment. Telephone assessments for adverse events occur during weeks 2, 3 and 6 after the study enema and at months 3 and 6. Patients who have had at least one recurrence after a primary episode and have completed at least one round of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization within the last year may be eligible for the study. Study Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded RBX2660 enema.

Study Design

Study Type:

Interventional

Actual Enrollment :

267 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Prospective, Randomized, Double-blinded, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of RBX2660 (Microbiota Suspension) for the Prevention of Clostridium Difficile Infection

Actual Study Start Date :

Jul 31, 2017

Actual Primary Completion Date :

Apr 2, 2020

Actual Study Completion Date :

Aug 3, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Group A Placebo is an enema of normal saline. Packaging and labeling are identical to the packaging and labeling for RBX2660 to support the study blinding	Drug: Placebo Placebo is normal saline solution administered as an enema Other Names: saline solution
Experimental: Group B RBX2660 is an enema of a microbiota suspension in a 0.9% sodium chloride irrigation USP solution and cryoprotectant	Drug: RBX2660 RBX2660 is a microbiota suspension administered as an enema Other Names: microbiota suspension

Arm

Intervention/Treatment

Placebo Comparator: Group A

Placebo is an enema of normal saline. Packaging and labeling are identical to the packaging and labeling for RBX2660 to support the study blinding

Drug: Placebo

Placebo is normal saline solution administered as an enema

Other Names:

saline solution

Experimental: Group B

RBX2660 is an enema of a microbiota suspension in a 0.9% sodium chloride irrigation USP solution and cryoprotectant

Drug: RBX2660

RBX2660 is a microbiota suspension administered as an enema

Other Names:

microbiota suspension

Outcome Measures

Primary Outcome Measures

Efficacy of RBX2660 compared to Placebo measured at 8 weeks [1, 4, and 8 weeks after completing the study treatment]
The absence of C. difficile diarrhea without the need for retreatment as assessed by subject interview and physical exam 1, 4, and 8 weeks after administration of the study treatment.

Secondary Outcome Measures

Number of subjects with adverse events through 6 months [Up to 6 months after completing the study treatment]
Documented adverse events will be categorized by frequency, severity, seriousness, and causality as assessed by subject interview and physical exam at 1-week, 4-week, and 8-week visits, and by subject phone interviews at 3 and 6 months from the last study treatment received.
Health Related Quality of Life (HRQOL) Assessment [Up to 6 months after completing the study treatment]
Screening HRQOL scores will be compared to scores obtained at the 1-Week, 4-week, and 8-week assessment visits, and 3 and 6 month phone assessments

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥ 18 years old.
Medical record documentation of recurrent CDI per the study definition, that includes either: a) at least one recurrence after a primary episode and has completed at least one round of standard-of-care oral antibiotic therapy or b) has had at least two episodes of severe CDI resulting in hospitalization within the last year.
A positive stool test for the presence of toxigenic C. difficile within 30 days prior to or on the date of enrollment.
Is currently taking or was just prescribed antibiotics to control CDI related diarrhea at the time of enrollment.

[Note: Subject's CDI diarrhea must be controlled (<3 unformed/loose stools/day) while taking this course of antibiotics]

Exclusion Criteria:

Currently has continued CDI diarrhea despite being on antibiotics prescribed for CDI treatment.
Previous fecal transplant
History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.
Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria.
Compromised immune system (e.g. immunosuppressed due to a medical condition or medication; current or recent (< 90 days) treatment with chemotherapy)
An absolute neutrophil count of <1000 cells/µL during screening.
Pregnant, breastfeeding, or intends to become pregnant during study participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Athens	Athens	Alabama	United States	35611
2	Dothan	Dothan	Alabama	United States	36305
3	Phoenix	Phoenix	Arizona	United States	85054
4	North Little Rock	North Little Rock	Arkansas	United States	72117
5	Lancaster	Lancaster	California	United States	93534
6	Los Angeles	Los Angeles	California	United States	90095
7	Oxnard	Oxnard	California	United States	93030
8	Sacramento	Sacramento	California	United States	95817
9	Aurora	Aurora	Colorado	United States	80045
10	Hamden	Hamden	Connecticut	United States	06518
11	Gainesville	Gainesville	Florida	United States	32610
12	Jacksonville	Jacksonville	Florida	United States	32224
13	Miami	Miami	Florida	United States	33176
14	Port Orange	Port Orange	Florida	United States	32127
15	Atlanta	Atlanta	Georgia	United States	30322
16	Atlanta	Atlanta	Georgia	United States	30342
17	Idaho Falls	Idaho Falls	Idaho	United States	83404
18	Gurnee	Gurnee	Illinois	United States	60031
19	Highland Park	Highland Park	Illinois	United States	60035
20	Maywood	Maywood	Illinois	United States	60153
21	Lafayette	Lafayette	Indiana	United States	47904
22	Topeka	Topeka	Kansas	United States	66606
23	Wichita	Wichita	Kansas	United States	67214
24	Lexington	Lexington	Kentucky	United States	40536
25	New Orleans	New Orleans	Louisiana	United States	70121
26	Shreveport	Shreveport	Louisiana	United States	71105
27	Boston	Boston	Massachusetts	United States	02114
28	Detroit	Detroit	Michigan	United States	48202
29	Plymouth	Plymouth	Minnesota	United States	55446
30	Rochester	Rochester	Minnesota	United States	55902
31	St. Louis	Saint Louis	Missouri	United States	63110
32	Omaha	Omaha	Nebraska	United States	68198-4031
33	Omaha	Omaha	Nebraska	United States	68198
34	Las Vegas	Las Vegas	Nevada	United States	89106
35	Teaneck	Teaneck	New Jersey	United States	07666
36	New York	New York	New York	United States	10016
37	North Massapequa	North Massapequa	New York	United States	11758
38	Rochester	Rochester	New York	United States	14618
39	Durham	Durham	North Carolina	United States	27710
40	Greenville	Greenville	North Carolina	United States	27834
41	Wilmington	Wilmington	North Carolina	United States	28401
42	Fargo	Fargo	North Dakota	United States	58102
43	Toledo	Toledo	Ohio	United States	43608
44	Portland	Portland	Oregon	United States	97701
45	Flourtown	Flourtown	Pennsylvania	United States	19031
46	Philadelphia	Philadelphia	Pennsylvania	United States	19102
47	Philadelphia	Philadelphia	Pennsylvania	United States	19107-5244
48	Uniontown	Uniontown	Pennsylvania	United States	15401
49	Wyomissing	Wyomissing	Pennsylvania	United States	19610
50	Charleston	Charleston	South Carolina	United States	29425
51	Rapid City	Rapid City	South Dakota	United States	57701
52	Hixson	Hixson	Tennessee	United States	37434
53	Dallas	Dallas	Texas	United States	75246
54	Houston	Houston	Texas	United States	77030
55	West Jordan	West Jordan	Utah	United States	84088
56	Springfield	Springfield	Virginia	United States	22150
57	Winchester	Winchester	Virginia	United States	22601
58	Seattle	Seattle	Washington	United States	98104
59	Madison	Madison	Wisconsin	United States	53792
60	Marshfield	Marshfield	Wisconsin	United States	54449
61	Calgary	Calgary	Alberta	Canada	T2N2T9
62	Edmonton	Edmonton	Alberta	Canada	TG2X8
63	Vancouver	Vancouver	British Columba	Canada	V5Z1M9
64	Victoria	Victoria	British Columbia	Canada	BC V8R 1J8
65	Fredericton	Fredericton	New Brunswick	Canada	E3B 4R3
66	Moncton	Moncton	New Brunswick	Canada	E1C628