Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001103954
Ethics application status
Approved
Date submitted
24/09/2020
Date registered
23/10/2020
Date last updated
29/06/2022
Date data sharing statement initially provided
23/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Seamless Phase 1b Study to Evaluate Safety, Tolerability and Efficacy of SER-301 in Adult Subjects with Active Mild-to-Moderate Ulcerative Colitis (Part 2)
Scientific title
A Seamless Phase 1b Study to Evaluate Safety, Tolerability and Efficacy of SER-301 in Adult Subjects with Active Mild-to-Moderate Ulcerative Colitis (Part 2)
Secondary ID [1] 302382 0
SER-301-001
Universal Trial Number (UTN)
U1111-1253-4503
Trial acronym
Linked study record
ACTRN12620000963921 is Part 1 of this 2-part Phase 1b study.

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 319169 0
Condition category
Condition code
Oral and Gastrointestinal 317134 317134 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a seamless Phase 1b multicentre study to evaluate safety, tolerability, and efficacy of SER-301 in adult participants with active mild-to-moderate UC.

SER-301 is a live microbiome therapeutic - a designed set of 18 live human-commensal bacterial strains representing different species administered as oral capsules. Each strain was purified from the stool of healthy donors and used to establish pure bacterial cell lines suitable for further good manufacturing practice use. The strains were selected based on their pharmacological properties and safety profile, including genomic and microbiological characterisation of the strains.

SER-301 drug product consists of 2 different capsule types each containing a different formulation containing a part of the total SER-301 composition. Two capsules of each part are delivered in the complete dose for a total of 4 capsules once-daily, or 5.1 x 10^7 colony forming units (CFU).
• SER-301 Part 1 is a liquid formulation of bacterial spores containing 10 strains delivered in 2 oral capsules. Part 1 contains 5.6 x 10^6 CFU.
• SER-301 Part 2 is a dry powder formulation of vegetative bacteria containing 8 strains delivered in 2 oral capsules. Part 2 contains 4.5 x 10^7 CFU.

This study has a seamless design, as it is composed of two study parts, with an operationally seamless transition in between. Both study parts share objectives of safety, tolerability, and engraftment measures. Part 2 also has some additional clinical and exploratory objectives.

Participants will be enrolled into either Part 1 or Part 2 of the study, but not both. This record describes Part 2 only.

Part 2 is randomised, double-blind, placebo-controlled. Approximately 50 participants will be randomised 2:3 to receive either 10 weeks of once-daily placebo following 6 days of placebo (4 times daily) or 10 weeks of once-daily induction treatment with SER-301 following 6 days of vancomycin pre-conditioning (125mg oral capsules, 4 times daily), respectively.

Adherence will be monitored throughout the study. All remaining drug should be returned by participants to the clinical site where drug accountability, including capsule count to monitor compliance, will take place and participants will also be asked to complete a diary where they will record daily symptoms.
Intervention code [1] 318664 0
Treatment: Drugs
Comparator / control treatment
SER-301 Placebo will be prepared using similar substances as SER-301 but without the active bacterial components.

Placebo for the spore component of the SER-301 drug product capsules will consist of a glycerol and saline solution filled into blue size 0 hydroxypropylmethylcellulose capsules.

Placebo for the vegetative component of the SER-301 drug product capsules will consist of microcrystalline cellulose and Aerosil R972 filled into natural size 0 capsules and sealed with an enteric coating.

Vancomycin Placebo will mimic the vancomycin capsules but will not contain vancomycin.

Vancomycin Placebo will be manufactured in size 00 gelatin Swedish Orange Capsules filled with microcrystalline cellulose.
Control group
Placebo

Outcomes
Primary outcome [1] 325214 0
Part 2 (Placebo-Controlled)

Primary Endpoint: Safety & tolerability of SER-301

The evaluation of safety data will be performed by descriptively summarising various safety parameters for patients treated with SER-301 and placebo. The following safety endpoints will be measured:
• Incidence of AEs, SAEs and AESIs
• Laboratory results
- Haematology (Erythrocytes, Hemoglobin, Hematocrit, MCV, MCH, MCHC, Leukocytes, Neutrophils (%, abs.), Lymphocytes (%, abs.), Monocytes (%, abs.), Eosinophils (%, abs.), Basophils (%, abs.), Platelets)
- Blood Chemistry (Sodium, Potassium, Albumin, Glucose(random), Triglycerides, Total Cholesterol, Creatinine, Uric Acid, Blood urea nitrogen, AST, ALT, Alkaline phosphatase, GGT, Bilirubin (total, direct, indirect), CRP)
- Urinalysis (pH, Specific gravity, Blood, Protein, Glucose, Leukocytes, Bilirubin, Ketones, Urobilinogen, Nitrites, RBC, WBC, Bacteria, Casts, Crystals, Yeasts, Epithelial Cells)
• Vital sign measurements
• Physical examination findings
Timepoint [1] 325214 0
After the pre-conditioning period (Week 1), after 10 weeks of induction treatment (Week 11), and 4 weeks after the last treatment dose (Week 15).
Secondary outcome [1] 387211 0
Part 2 (Placebo-Controlled)

Secondary Endpoint: Endoscopic improvement (an endoscopic score decrease from baseline of at least 1 point) with SER-301 induction treatment (following vancomycin pre-conditioning), compared to placebo, as determined by an independent, blinded central reader.
Timepoint [1] 387211 0
After 10 weeks of induction treatment.
Secondary outcome [2] 387212 0
Part 2 (Placebo-Controlled)

Secondary Endpoint: Engraftment of SER-301 bacteria

Engraftment of SER-301 strains will be assessed by examining the number of SER-301 strains present in participant stool following treatment as compared with their presence before treatment and with the prevalence of strains in placebo subjects.
Timepoint [2] 387212 0
After 10 weeks of induction treatment.

Eligibility
Key inclusion criteria
Inclusion Criteria

Documented diagnosis of UC prior to screening endoscopy

Active mild-to-moderate UC as determined by a 3-Component Modified Mayo Score

Minimum disease extent of 15 cm from the anal verge, confirmed at the screening endoscopy

Naïve to UC treatment or with an inadequate response to, loss of response to, or intolerance of, at least one of the following conventional therapies: 5-ASA compounds, corticosteroids or immunomodulators (e.g., 6-MP, AZA, methotrexate)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Known history of Crohn’s disease

On steroid medication who are unable to have steroids tapered, and be completely off steroids at least 2 weeks prior to screening

Unable to stop steroid enemas or suppositories, or 5-ASA enemas or suppositories, at least 2 weeks prior to screening

Previously received any investigational or approved biologic therapy

Previously received any investigational or approved non-biologic therapy, except for those specifically listed in the Permitted Concomitant Medications (e.g., stable dose of 6-MP, AZA, methotrexate)

Major gastrointestinal surgery (not including appendectomy or cholecystectomy) within 2 months prior to screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The Study has been terminated prematurely based on Cohort 1 data.
Date of first participant enrolment
Anticipated
28/12/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 17620 0
University of Sunshine Coast Health Clinics - Sippy Downs
Recruitment hospital [2] 17621 0
Gold Coast University Hospital - Southport
Recruitment hospital [3] 17622 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [4] 17623 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [5] 17624 0
Mater Private Hospital - South Brisbane
Recruitment hospital [6] 17626 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [7] 17628 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 20582 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [9] 20583 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [10] 20584 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [11] 20585 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [12] 20586 0
Box Hill Hospital - Box Hill
Recruitment hospital [13] 20587 0
Emeritus Research - Camberwell
Recruitment hospital [14] 20588 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [15] 20589 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 35374 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 35372 0
2050 - Camperdown
Recruitment postcode(s) [3] 31367 0
2109 - Macquarie Park
Recruitment postcode(s) [4] 35371 0
2200 - Bankstown
Recruitment postcode(s) [5] 31371 0
3065 - Fitzroy
Recruitment postcode(s) [6] 35373 0
3084 - Heidelberg
Recruitment postcode(s) [7] 35376 0
3124 - Camberwell
Recruitment postcode(s) [8] 35375 0
3128 - Box Hill
Recruitment postcode(s) [9] 35377 0
3220 - Geelong
Recruitment postcode(s) [10] 31369 0
4101 - South Brisbane
Recruitment postcode(s) [11] 31366 0
4215 - Southport
Recruitment postcode(s) [12] 31365 0
4556 - Sippy Downs
Recruitment postcode(s) [13] 31373 0
5000 - Adelaide
Recruitment postcode(s) [14] 31368 0
6008 - Subiaco
Recruitment postcode(s) [15] 35370 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 23010 0
New Zealand
State/province [1] 23010 0
Wellington
Country [2] 23011 0
New Zealand
State/province [2] 23011 0
Auckland

Funding & Sponsors
Funding source category [1] 306810 0
Commercial sector/Industry
Name [1] 306810 0
Seres Therapeutics, Inc.
Country [1] 306810 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
PSI CRO Australia Pty. Ltd.
Address
Suite 2.01
16 Giffnock Avenue
Macquarie Park
NSW 2113
Country
Australia
Secondary sponsor category [1] 307362 0
None
Name [1] 307362 0
Address [1] 307362 0
Country [1] 307362 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306966 0
Bellberry HREC G
Ethics committee address [1] 306966 0
123 Glen Osmond Road
Eastwood
South Australia 5063
Ethics committee country [1] 306966 0
Australia
Date submitted for ethics approval [1] 306966 0
03/06/2020
Approval date [1] 306966 0
31/07/2020
Ethics approval number [1] 306966 0
Ethics committee name [2] 306968 0
Gold Coast Hospital and Health Service HREC
Ethics committee address [2] 306968 0
1 Hospital Boulevard
Southport
Queensland 4215
Ethics committee country [2] 306968 0
Australia
Date submitted for ethics approval [2] 306968 0
10/06/2020
Approval date [2] 306968 0
12/08/2020
Ethics approval number [2] 306968 0
Ethics committee name [3] 306969 0
Macquarie University HREC (Medical Sciences)
Ethics committee address [3] 306969 0
Balaclava Road
North Ryde
New South Wales 2109
Ethics committee country [3] 306969 0
Australia
Date submitted for ethics approval [3] 306969 0
18/08/2020
Approval date [3] 306969 0
24/09/2020
Ethics approval number [3] 306969 0
Ethics committee name [4] 306970 0
St John of God Healthcare HREC
Ethics committee address [4] 306970 0
12 Salvado Road
Subiaco
Western Australia 6008
Ethics committee country [4] 306970 0
Australia
Date submitted for ethics approval [4] 306970 0
13/07/2020
Approval date [4] 306970 0
12/08/2020
Ethics approval number [4] 306970 0
Ethics committee name [5] 306973 0
Central Adelaide Local Health Network HREC
Ethics committee address [5] 306973 0
Level 3, Roma Mitchell House
136 North Terrace
Adelaide, South Australia, 5000
Ethics committee country [5] 306973 0
Australia
Date submitted for ethics approval [5] 306973 0
04/09/2020
Approval date [5] 306973 0
27/01/2021
Ethics approval number [5] 306973 0
Ethics committee name [6] 306975 0
Northern B Health and Disability Ethics Committee
Ethics committee address [6] 306975 0
Ministry of Health
PO Box 5013
Wellington 6140
Ethics committee country [6] 306975 0
New Zealand
Date submitted for ethics approval [6] 306975 0
18/06/2020
Approval date [6] 306975 0
29/09/2020
Ethics approval number [6] 306975 0

Summary
Brief summary
This is a seamless Phase 1b multicentre study to evaluate safety, tolerability, and efficacy of SER-301 in adult participants with active mild-to-moderate UC.

SER-301 is a live microbiome therapeutic – a designed set of diverse, human-commensal bacterial strains, administered as oral capsules.

This study has a seamless design, as it is composed of two study parts, each with different objectives, with an operationally seamless transition in between.

Participants will be enrolled into either Part 1 or Part 2.

Part 2 is randomised, double-blind, placebo-controlled. Approximately 50 participants will be randomised 2:3 to receive either 10 weeks of once-daily placebo following 6 days of placebo (4 times daily) or 10 weeks of once-daily induction treatment with SER-301 following 6 days of vancomycin pre-conditioning (4 times daily), respectively.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105614 0
Dr Susan Thackwray
Address 105614 0
University of the Sunshine Coast Clinical Trials
90 Sippy Downs Drive
Sippy Downs
Queensland 4556
Country 105614 0
Australia
Phone 105614 0
+61 07 5456 3797
Fax 105614 0
Email 105614 0
CTC@usc.edu.au
Contact person for public queries
Name 105615 0
Ms Mildred Danao
Address 105615 0
PSI CRO Australia Pty. Ltd.
Suite 2.01
16 Giffnock Avenue
Macquarie Park
New South Wales 2113
Country 105615 0
Australia
Phone 105615 0
+61 02 8582 1682
Fax 105615 0
Email 105615 0
mildred.danao@psi-cro.com
Contact person for scientific queries
Name 105616 0
Ms Mildred Danao
Address 105616 0
PSI CRO Australia Pty. Ltd.
Suite 2.01
16 Giffnock Avenue
Macquarie Park
New South Wales 2113
Country 105616 0
Australia
Phone 105616 0
+61 02 8582 1682
Fax 105616 0
Email 105616 0
mildred.danao@psi-cro.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.