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Trial registered on ANZCTR


Registration number
ACTRN12620000932965
Ethics application status
Approved
Date submitted
27/07/2020
Date registered
18/09/2020
Date last updated
18/09/2020
Date data sharing statement initially provided
18/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 study dosing with a Humira® (adalimumab) Enema in Patients with Active Ulcerative Colitis.
Scientific title
Phase 1 Open-Label Study to Assess Pharmacokinetic and Pharmacodynamic Parameters Following Dosing with an Anti-Tumor Necrosis Factor Monoclonal Antibody (Humira®, adalimumab) Enema in Patients with Active Ulcerative Colitis.
Secondary ID [1] 299935 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative colitis 315370 0
Condition category
Condition code
Oral and Gastrointestinal 313673 313673 0 0
Inflammatory bowel disease
Inflammatory and Immune System 316705 316705 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 316707 316707 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 Phase 1 study will assess the PK/PD parameters following dosing with adalimumab administered rectally as an enema in subjects with active UC.

Eligible participants will receive adalimumab daily on Days 1, 2, and 3.

The initial participants (N=3) enrolled will receive 160mg adalimumab daily for 3 days administered rectally as an enema. If there is adequate drug in the tissue, the dose of adalimumab will be administered at 80mg daily for 3 days for the remaining subjects (up to 9). If there is inadequate adalimumab in the tissues at the highest dose of 160 mg adalimumab, the study may be stopped.

The adalimumab enema will, on all occasions, be administered to the participant in the clinic by the study team.
Intervention code [1] 316202 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322096 0
To assess safety and tolerability of 3 daily doses of adalimumab.administration via enema to patients with active ulcerative colitis (UC).
Timepoint [1] 322096 0
AEs will be assessed from Screening through end of study Day 30 via the following:

Clinical Laboratory test samples taken at::
Screening Visit
Days 1, 8 and 30 after intervention commencement or early termination

Vital sign measurements taken at:
Screening Visit
Days 1, 2, 3, 4, 5, 8, 22 and 30 after intervention commencement or early termination

Participant Diary for the recording of any changes in health and medications from::
- Day 1 to Day 14
Primary outcome [2] 323486 0
To assess local tissue PK of adalimumab after administration via enema to patients with active UC.

The PK profile of adalimumab in tissue will be assessed via population PK modelling. Furthermore, the analysis of tissue PK will be performed using samples from the UC disease affected area, and separately, unaffected area. Multiple concentration values from repeat samples of the same area type will be averaged prior to analysis.
Timepoint [2] 323486 0
Sigmoidoscopy with biopsy of UC disease affected and unaffected areas will be performed at Screening and Days 4, 5 and 8 and will be assessed to obtain adalimumab PK concentrations.

Please note, the initial 3 participants will have post-treatment sigmoidoscopies with biopsy on Days 4, 5 and 8. The timing of the post-treatment sigmoidoscopies with biopsy may be adjusted for subsequent participants to ensure samples are taken at the optimal time points for sample collection. No sigmoidoscopy will occur after Day 14.
Secondary outcome [1] 377324 0
To assess local tissue PD changes after adalimumab administration via enema to patients with active UC:
Timepoint [1] 377324 0
Sigmoidoscopy with biopsy of UC disease affected and unaffected areas will be performed at Days 1, 4, 5 and 8 and will be assessed to obtain tissue PD biomarker levels of RNA expression and protein concentration ( including but not limited to TNFa, IL-6, and IL 10).
Secondary outcome [2] 384490 0
To assess systemic PK after adalimumab administration via enema to patients with active UC.

PK parameters such as Tmax, AUC and T1/2 in serum and tissue will be assessed,
Timepoint [2] 384490 0
PK blood samples will be collected at:
Days 1, 2 and 3 (pre-dose, 30 minutes, 60 minutes and 120 minutes post drug administration)
Days 4, 5 and 8 (prior to each post-treatment sigmoidoscopy)
Day 30 after intervention commencement or early termination

Tissue PK samples will be collected through biopsy at screening and post-treatment sigmoidoscopy on Days 4, 5, and 8.
Secondary outcome [3] 385902 0
To assess systemic PD changes after adalimumab administration via enema to patients with active UC.

Changes in PD biomarker levels of Calprotectin, CRP, HSA, TNF and IL-6 in serum and tissue will be assessed. Also changes in Histology, Mayo Scores and Robarts Histological Index Scores will be assessed.
Timepoint [3] 385902 0
PD blood samples will be collected at:
Days 1, 2 and 3 (pre-dose, 30 minutes, 60 minutes and 120 minutes post drug administration)
Days 4, 5 and 8 (prior to each post-treatment sigmoidoscopy)
Day 30 after intervention commencement or early termination

Tissue PK samples will be collected through biopsy at screening and post-treatment sigmoidoscopy on Days 4, 5, and 8.

Eligibility
Key inclusion criteria
- Subject must provide consent to participate in the study prior to any study procedures are performed
- UC diagnosis for at least 3 months. .
- Active colitis:
- Drug stabilisation requirements, if on one or more of the following medications: oral corticosteroid treatment, oral aminosalicylates, Azathioprine or 6 mercaptopurine, Vedolizumab, Tofacitinib, Ustekinumab
- Women of childbearing potential must agree to use birth control
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Diagnosis of (or clinical findings suggestive of) Crohn’s disease or indeterminate colitis
- Diagnosis of UC limited to rectum
- Evidence of fulminant colitis
- Need for colostomy or ileostomy (within 3 months)
- Previous total or subtotal colectomy or any surgical resection
- Prior exposure to adalimumab
- Prior hypersensitivity reaction to any anti TNF therapy
- Recent or current use of any anti TNF agent
- Current rectal therapy for UC
- Current use of intravenous corticosteroid for UC
- History of renal insufficiency or failure
- History of untreated colonic dysplasia
- Planned surgery over the duration of the study
- History of drug or alcohol abuse
- History of tuberculosis (TB) exposure or latent TB
- Evidence of invasive fungal infections
- History of central or peripheral nervous system demyelinating disorders
- History of congestive heart failure
- Evidence of HIV, hepatitis B, or hepatitis C
- Evidence of active cytomegalovirus (CMV) infection or CMV colitis
- Recent or current need for a live vaccine
- Positive stool culture for enteric pathogens
- Stool positive for Clostridium difficile toxin
- Recent treatment with an investigational (chemical or biological) product
- Women who are lactating or breast-feeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 15348 0
Mater Private Hospital - South Brisbane
Recruitment hospital [2] 15349 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 28659 0
4101 - South Brisbane
Recruitment postcode(s) [2] 28660 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 304396 0
Commercial sector/Industry
Name [1] 304396 0
Progenity Inc.
Address [1] 304396 0
4330 La Jolla Village Dr., Suite 200
San Diego, CA 92122
Country [1] 304396 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Progenity Inc
Address
4330 La Jolla Village Dr., Suite 200
San Diego, CA 92122
Country
United States of America
Secondary sponsor category [1] 304654 0
None
Name [1] 304654 0
Address [1] 304654 0
Country [1] 304654 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304833 0
The Prince Charles Hospital Human Research Ethics Committee
Ethics committee address [1] 304833 0
Building 14
Rode Road
CHERMSIDE QLD 4032
Ethics committee country [1] 304833 0
Australia
Date submitted for ethics approval [1] 304833 0
Approval date [1] 304833 0
09/04/2020
Ethics approval number [1] 304833 0
Ethics committee name [2] 306486 0
Central Adelaide Local Health Network (CALHN) Human Research Ethics Committee
Ethics committee address [2] 306486 0
Level 3, Roma Mitchell House
136 North Terrace
Adelaide,
South Australia, 5000
Ethics committee country [2] 306486 0
Australia
Date submitted for ethics approval [2] 306486 0
Approval date [2] 306486 0
Ethics approval number [2] 306486 0

Summary
Brief summary
Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon and is associated with significant morbidity and impairment to quality of life. Adalimumab is approved and marketed in Australia, US and EU for treatment of UC. Its efficacy is suboptimal when given subcutaneously. This Phase 1 study will assess the PK/PD parameters following dosing with adalimumab administered rectally as an enema in subjects with active UC. Rectal administration will bring the drug into closer proximity with the inflamed tissues at much higher local concentrations compared to subcutaneous
administration. As the Sponsor is developing an ingestible drug/device capsule intended to deliver the drug payload (adalimumab) into the cecum, the rectal administration via an enema was chosen as an initial step to assess the absorption of adalimumab across the mucosal/epithelial interface of the cecum. Data obtained from this study will assist in determining the starting dose/dose regimen for the Progenity PGN 001 program by providing further understanding of absorption, bioavailability, and the early safety data of adalimumab following local administration in subjects with UC in local tissues as well as systemically.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98358 0
A/Prof Jakob Begun
Address 98358 0
Mater Misericordiae Ltd,
Gastroenterology Department,
Salmon Building, Level 4,
Raymond Terrace,
South Brisbane,
Queensland 4101
Country 98358 0
Australia
Phone 98358 0
+61 7 3163 2371
Fax 98358 0
Email 98358 0
jakob.begun@mater.uq.edu.au
Contact person for public queries
Name 98359 0
Dr Emil Chuang
Address 98359 0
Progenity Inc.
4330 La Jolla Village Dr., Suite 200
San Diego, CA 92122
Country 98359 0
United States of America
Phone 98359 0
+1 858 260 5221
Fax 98359 0
Email 98359 0
Emil.Chuang@progenity.com
Contact person for scientific queries
Name 98360 0
Dr Emil Chuang
Address 98360 0
Progenity Inc.
4330 La Jolla Village Dr., Suite 200
San Diego, CA 92122
Country 98360 0
United States of America
Phone 98360 0
+1 858 260 5221
Fax 98360 0
Email 98360 0
Emil.Chuang@progenity.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 other documents available
Summary results
No Results