Trial Outcomes & Findings for Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (NCT NCT02589847)

Last Updated: 2021-03-26

Results Overview

Participants were evaluated 8 weeks after study treatment to assess efficacy of RBX2660. Efficacy was assessed as the absence of CDI diarrhea without the need for retreatment with C. difficile anti-infective therapy or fecal transplant through 56 days after completion of study treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

272 participants

Primary outcome timeframe

8 weeks after treatment

Results posted on

2021-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	RBX2660 Open-label RBX2660 (microbiota suspension) RBX2660: suspension of intestinal microbes	Historical Control Antibiotics Retrospective Historical Control with standard of care Standard of Care Antibiotics: Standard of Care Antibiotics
Overall Study STARTED	162	110
Overall Study Safety Population	149	0
Overall Study Full Analysis Set (FAS)	149	104
Overall Study Evaluable	142	75
Overall Study COMPLETED	107	39
Overall Study NOT COMPLETED	55	71

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RBX2660 Open-label n=149 Participants RBX2660 (microbiota suspension) RBX2660: suspension of intestinal microbes	Historical Control Antibiotics n=104 Participants Retrospective Historical Control with standard of care Standard of Care Antibiotics: Standard of Care Antibiotics	Total n=253 Participants Total of all reporting groups
Age, Categorical >=65 years	87 Participants n=5 Participants	64 Participants n=7 Participants	151 Participants n=5 Participants
Sex: Female, Male Female	95 Participants n=5 Participants	71 Participants n=7 Participants	166 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	33 Participants n=7 Participants	87 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	62 Participants n=5 Participants	40 Participants n=7 Participants	102 Participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	142 Participants n=5 Participants	44 Participants n=7 Participants	186 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	55 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	136 Participants n=5 Participants	40 Participants n=7 Participants	176 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	16 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	45 Participants n=7 Participants	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks after treatment

Population: Evaluable Population - All participants evaluable for a treatment outcome through 56 days after completion of treatment.

Outcome measures

Outcome measures
Measure	RBX2660 Open-label n=142 Participants RBX2660 (microbiota suspension) RBX2660: suspension of intestinal microbes	Historical Control Antibiotics n=75 Participants Retrospective Historical Control with standard of care Standard of Care Antibiotics: Standard of Care Antibiotics
Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks Treatment Success	112 Participants	23 Participants
Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks Treatment Failure	30 Participants	52 Participants

SECONDARY outcome

Timeframe: Baseline

Population: Safety Population - The SP includes all participants who were enrolled and received at least dose of RBX2660.

The Short Form - 36 quality of life questionnaire (SF-36) is a tool used to identify changes to quality of life following study treatment. It consists of a series of 36 questions relating to Mental and Physical health, summarized by a Physical Component Score (PCS) and Mental Component Score (MCS), respectively. Several sub-scales exist for each of the larger components; PCS includes PF, RP, BP, and GH while, MCS includes VT, SF, RE, and MH \[All abbreviations are defined in table\]. All Sub-Scale and Component Scores were calculated using Quality Metric Health Outcomes Scoring Software v4.5. The range of all scores is normalized from 0 (worst) to 100 (best). The data is presented for mean scores at baseline and 8-weeks post-treatment.

Outcome measures

Outcome measures
Measure	RBX2660 Open-label n=149 Participants RBX2660 (microbiota suspension) RBX2660: suspension of intestinal microbes	Historical Control Antibiotics Retrospective Historical Control with standard of care Standard of Care Antibiotics: Standard of Care Antibiotics
Quality of Life (SF-36) Role Limitations Due to Emotional Problems (RE)	43.6 score on a scale Standard Deviation 12.2	—
Quality of Life (SF-36) Physical Component Summary (PCS)	40.3 score on a scale Standard Deviation 9.3	—
Quality of Life (SF-36) Physical Functioning (PF)	39.8 score on a scale Standard Deviation 11.8	—
Quality of Life (SF-36) Role Limitations Due to Physical Health (RP)	38.0 score on a scale Standard Deviation 11.3	—
Quality of Life (SF-36) Bodily Pain (BP)	44.5 score on a scale Standard Deviation 11.5	—
Quality of Life (SF-36) General Health Perceptions (GH)	44.6 score on a scale Standard Deviation 10.7	—
Quality of Life (SF-36) Mental Component Summary (MCS)	45.5 score on a scale Standard Deviation 12.3	—
Quality of Life (SF-36) Vitality (VT)	41.9 score on a scale Standard Deviation 11.5	—
Quality of Life (SF-36) Social Functioning (SF)	40.1 score on a scale Standard Deviation 12.2	—
Quality of Life (SF-36) Mental Health (MH)	46.3 score on a scale Standard Deviation 11.7	—

SECONDARY outcome

Timeframe: 8-Weeks

Population: Safety Population - The SP includes all participants who were enrolled and received at least dose of RBX2660.

Outcome measures

Outcome measures
Measure	RBX2660 Open-label n=149 Participants RBX2660 (microbiota suspension) RBX2660: suspension of intestinal microbes	Historical Control Antibiotics Retrospective Historical Control with standard of care Standard of Care Antibiotics: Standard of Care Antibiotics
Quality of Life (SF-36) Mental Health (MH)	51.0 score on a scale Standard Deviation 10.6	—
Quality of Life (SF-36) Physical Component Summary (PCS)	44.3 score on a scale Standard Deviation 11.1	—
Quality of Life (SF-36) Physical Functioning (PF)	42.2 score on a scale Standard Deviation 12.6	—
Quality of Life (SF-36) Role Limitations Due to Physical Health (RP)	43.8 score on a scale Standard Deviation 10.7	—
Quality of Life (SF-36) Bodily Pain (BP)	48.6 score on a scale Standard Deviation 11.8	—
Quality of Life (SF-36) General Health Perceptions (GH)	48.0 score on a scale Standard Deviation 10.0	—
Quality of Life (SF-36) Mental Component Summary (MCS)	50.9 score on a scale Standard Deviation 10.4	—
Quality of Life (SF-36) Vitality (VT)	49.0 score on a scale Standard Deviation 10.5	—
Quality of Life (SF-36) Social Functioning (SF)	47.2 score on a scale Standard Deviation 11.3	—
Quality of Life (SF-36) Role Limitations Due to Emotional Problems (RE)	46.9 score on a scale Standard Deviation 11.8	—

SECONDARY outcome

Timeframe: 24 months

Population: Full Analysis Set- Defined as participants who received at least one dose of RBX2660 or was in the Historical Control Arm

Major complications of rCDI, defined as death, septic shock, toxic megacolon, colonic perforation, emergency colectomy, or ICU admission) were collected and reported as a safety-related endpoint.

Outcome measures

Outcome measures
Measure	RBX2660 Open-label n=149 Participants RBX2660 (microbiota suspension) RBX2660: suspension of intestinal microbes	Historical Control Antibiotics n=104 Participants Retrospective Historical Control with standard of care Standard of Care Antibiotics: Standard of Care Antibiotics
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months At least one complication of rCDI	3 Participants	2 Participants
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months Death	1 Participants	0 Participants
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months Septic Shock	2 Participants	1 Participants
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months Toxic Megacolon	0 Participants	0 Participants
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months Colonic Perforations	0 Participants	0 Participants
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months Emergency Colectomy	0 Participants	1 Participants
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months ICU Admission	2 Participants	0 Participants

Adverse Events

RBX2660 Open-label

Serious events: 52 serious events

Other events: 118 other events

Deaths: 15 deaths

Historical Control Antibiotics

Serious events: 30 serious events

Other events: 62 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Development

Rebiotix, Inc.

Phone: 651-705-8778

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	RBX2660 Open-label n=149 participants at risk RBX2660 (microbiota suspension) RBX2660: suspension of intestinal microbes	Historical Control Antibiotics n=104 participants at risk Retrospective Historical Control with standard of care Standard of Care Antibiotics: Standard of Care Antibiotics
Gastrointestinal disorders Diarrhoea	28.2% 42/149 • Number of events 69 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	7.7% 8/104 • Number of events 8 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Gastrointestinal disorders Abdominal pain	12.1% 18/149 • Number of events 30 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	0.96% 1/104 • Number of events 1 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Gastrointestinal disorders Flatulence	5.4% 8/149 • Number of events 9 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	0.96% 1/104 • Number of events 1 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Gastrointestinal disorders Constipation	11.4% 17/149 • Number of events 21 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	3.8% 4/104 • Number of events 9 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Gastrointestinal disorders Abdominal distension	6.0% 9/149 • Number of events 11 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	0.96% 1/104 • Number of events 2 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Gastrointestinal disorders Nausea	6.7% 10/149 • Number of events 15 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	1.9% 2/104 • Number of events 2 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Infections and infestations Urinary tract infection	11.4% 17/149 • Number of events 20 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	16.3% 17/104 • Number of events 22 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Nervous system disorders Headache	6.0% 9/149 • Number of events 9 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	5.8% 6/104 • Number of events 7 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Musculoskeletal and connective tissue disorders Back pain	4.7% 7/149 • Number of events 7 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	6.7% 7/104 • Number of events 10 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Nervous system disorders Dizziness	1.3% 2/149 • Number of events 2 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	5.8% 6/104 • Number of events 7 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
General disorders Fatigue	2.0% 3/149 • Number of events 4 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	8.7% 9/104 • Number of events 9 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
General disorders Asthenia	2.7% 4/149 • Number of events 4 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	6.7% 7/104 • Number of events 8 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
General disorders Oedema peripheral	1.3% 2/149 • Number of events 3 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	5.8% 6/104 • Number of events 11 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Infections and infestations Upper respiratory tract infection	5.4% 8/149 • Number of events 9 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	2.9% 3/104 • Number of events 3 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 2/149 • Number of events 2 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.	5.8% 6/104 • Number of events 8 • Adverse Events were collected from enrollment through 24 months after treatment for participants who received RBX2660. Historical Control subjects were followed for up to 6 months. Treatment emergent adverse events are presented, defined as adverse events that occurred after exposure to study drug. For participants that received RBX2660, at each contact point (in office visit or scheduled phone call) they were systematically asked about adverse events, as well as use of a subject diary for one week post the last study enema.