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A Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Mild-to-Moderate Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT02618187
Recruitment Status : Completed
First Posted : December 1, 2015
Results First Posted : June 20, 2019
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Seres Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE November 20, 2015
First Posted Date  ICMJE December 1, 2015
Results First Submitted Date  ICMJE September 25, 2018
Results First Posted Date  ICMJE June 20, 2019
Last Update Posted Date June 20, 2019
Actual Study Start Date  ICMJE January 13, 2016
Actual Primary Completion Date December 6, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • Safety and Tolerability of SER-287 [ Time Frame: Day 246 ]
    Treatment-Emergent Adverse Events Incidence by Treatment, System Organ Class and Preferred Term. The treatment period with SER-287 was eight weeks. All AEs were collected from the date of Informed Consent (up to 17 days of Screening) through Day 92 of the study. All SAEs were collected from the date of Informed Consent through Day 246 of the study.
  • Composition of the Intestinal Microbiome [ Time Frame: Baseline and 8 weeks ]
    Changes in the composition of the microbiome were characterized by whole metagenomic sequencing (WMS) of subjects' stool samples. Changes in the composition of the microbiome were measured by quantifying the number of unique types of spore-forming bacteria detected in subjects' stool samples after eight weeks of induction treatment versus baseline.
  • Engraftment of SER-287 Bacteria in All Treatment Arms [ Time Frame: Baseline and 8 weeks ]
    The stool microbiomes of SERES-101 subjects, before and after treatment with SER-287, were characterized using whole metagenomic sequencing (WMS). SER-287 drug product was also characterized using WMS. Microbiome engraftment was assessed by the number of spore-forming species in the drug product lots that were also detected in subjects' post-treatment fecal samples but not detected at baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: November 25, 2015)
  • Safety and tolerability of SER-287 vs. placebo in adult subjects by analysis of AE's, lab values, vital sign, physical exam findings, medical history, and ECG. [ Time Frame: Day 246 ]
  • Examination of baseline composition of the intestinal microbiome to the composition [ Time Frame: 8 weeks ]
    Changes in the composition of the microbiome will be characterized by rDNA 16S V4 genomic data sets. Changes will be assessed by total number of unique bacteria and microbial composition
  • Engraftment of SER-287 bacteria into the intestinal microbial community in each of the SER-287 arms compared to the placebo arm [ Time Frame: 8 weeks ]
    Microbiome will be characterized by rDNA 16S v4 Genomic Data Sets. Engraftment will be assessed as the outgrowth of bacteria that compromise the SER-287 spore ecology in the subjects GI tract post treatment
Change History Complete list of historical versions of study NCT02618187 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • Clinical Remission [ Time Frame: 8 weeks ]
    Defined as a Total Modified Mayo Score <= 2 and an endoscopic subscore <= 1. The Total Modified Mayo Score is a measure of UC disease activity which ranges from 0 to 12 points and consists of four subscores (stool frequency, rectal bleeding, endoscopy, and physician global assessment), each graded from 0 to 3, with higher scores indicating more severe disease. The four components are summed together for a composite score, with a higher overall score indicating more severe disease (0 = no disease; 12 = worst disease). The Modified Mayo endoscopic subscore excludes friability from an endoscopic subscore of 1.
  • Endoscopic Improvement [ Time Frame: 8 weeks ]
    Defined as a decrease in endoscopic subscore >= 1
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Mild-to-Moderate Ulcerative Colitis
Official Title  ICMJE A Phase 1B Multiple Dose Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Mild-to-Moderate Ulcerative Colitis
Brief Summary A Multiple Dose Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects with Mild-to-Moderate Ulcerative Colitis.
Detailed Description This is a Phase 1b multicenter, randomized, double-blind, placebo-controlled multiple dose study designed to evaluate the safety and tolerability of SER-287, and to evaluate the microbiome alterations and pharmacodynamics associated with two dosing regimens of SER-287 in adult subjects with active mild-to-moderate ulcerative colitis (UC).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE
  • Drug: SER-287
    Other Name: Eubacterial Spores, Purified Suspension, Encapsulated
  • Drug: Placebo
  • Drug: Placebo Pre-Treat
  • Drug: Vancomycin Pre-Treat
Study Arms  ICMJE
  • Experimental: Weekly SER-287, after Placebo Pre-Treat.
    Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
    Interventions:
    • Drug: SER-287
    • Drug: Placebo Pre-Treat
  • Placebo Comparator: Daily placebo, after Placebo Pre-Treat.
    Placebo pre-treatment, followed by once daily placebo for 8 weeks
    Interventions:
    • Drug: Placebo
    • Drug: Placebo Pre-Treat
  • Experimental: Daily SER-287, after Vanco. Pre-Treat.
    Vancomycin pre-treatment, followed by once daily dosing of SER-287 for 8 weeks
    Interventions:
    • Drug: SER-287
    • Drug: Vancomycin Pre-Treat
  • Experimental: Weekly SER-287, after Vanco. Pre-Treat.
    Vancomycin pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks
    Interventions:
    • Drug: SER-287
    • Drug: Vancomycin Pre-Treat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 23, 2018)
58
Original Estimated Enrollment  ICMJE
 (submitted: November 25, 2015)
55
Actual Study Completion Date  ICMJE January 26, 2018
Actual Primary Completion Date December 6, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ulcerative colitis diagnosed by routine clinical, radiographic, endoscopic and pathologic criteria (preferably confirmed by colonoscopy and pathology records within last 2 years or if unavailable, will need approval by medical monitor) Active mild-moderate UC as determined by sigmoidoscopy within approximately 3 days of randomization to study

Exclusion Criteria:

  1. Fever > 38.3°C
  2. Known or suspected toxic megacolon and/or known small bowel ileus
  3. Known history of Crohn's disease
  4. Subjects with serum albumin <2.5 g/dL at baseline
  5. CMV polymerase chain reaction (PCR) positive from blood plasma at screening
  6. Known stool studies positive for ova and/or parasites or stool culture within the 30 days before enrollment
  7. Subjects on cyclosporine or triple immunosuppression, Triple immunosuppression will include any three of the following classes of drugs taken in combination: steroids (i.e., prednisone/budesonide/budesonide MMX), immunosuppressant (i.e., methotrexate/azathioprine/6-mercaptopurine), and/or other immunosuppressant (i.e., tacrolimus, cellcept).
  8. Biologic medication (infliximab/ adalimumab/ golimumab/ certolizumab/vedolizumab/ustekinumab/natalizumab) use within 3 months prior to screening
  9. Known active malignancy except for basal cell skin cancer, squamous cell skin cancer
  10. Subjects with previous colectomy, ostomy, J-pouch, or previous intestinal surgery (excluding cholecystectomy, appendectomy)
  11. Subjects with known history of celiac disease or gluten enteropathy
  12. Subjects with Clostridium difficile positive stool at Screening Visit
  13. Antibiotic use within the prior 1 month before randomization
  14. Expected to receive antibiotics within 8 weeks of signing the Informed Consent Form (ICF) (i.e., for planned/anticipated procedure)
  15. Received an investigational drug within 1 month before study entry
  16. Received an investigational antibody or vaccine within 3 months before study entry
  17. Previously enrolled in a SER-109/SER-287 study
  18. Received an FMT within the last 6 months
  19. Subjects with anatomic or medical contraindications to flexible sigmoidoscopy, including but not necessarily limited to toxic megacolon, gastrointestinal (GI) fistulas, immediate post-operative status from abdominal surgery, severe coagulopathy, large or symptomatic abdominal aortic aneurysm, or any subject where study physician deems subject at significant risk of complications of flexible sigmoidoscopy
  20. Unable to stop steroid enemas or suppositories or mesalamine enemas or suppositories before screening visit
  21. Unable to stop opiate treatment unless on a stable dose and no increase in dose planned for the duration of the study
  22. Unable to stop probiotics before screening visit
  23. Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation with medical monitor)
  24. Known allergy or intolerance to oral vancomycin

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Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02618187
Other Study ID Numbers  ICMJE SERES-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Seres Therapeutics, Inc.
Study Sponsor  ICMJE Seres Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Seres Therapeutics, Inc.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP