None listed
Conditions
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.
Interventions
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 ther
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.
Sponsors
Progenity Inc
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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
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.
Outcome results
None listed