Ulcerative ColitisPhase 1NCT01759056
Evaluation of an Oral Anti-TNF Antibody in Patients With Active Ulcerative Colitis
A Phase 1 study testing AVX 470 in people with Ulcerative Colitis, run by Avaxia Biologics, Incorporated at 16 sites in 4 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability as well as the pharmacodynamic effects of multiple doses of AVX-470 administered orally in patients with active ulcerative colitis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- AVX 470
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 16 sitesin 4 countries
- Study dates
- Feb 2013to Dec 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women aged 18 75, inclusive
- Established diagnosis of ulcerative colitis involving the sigmoid colon or proximal segments of bowel
- Total Mayo score between 5-12, inclusive, with endoscopic subscore of the Mayo score ≥ 2 and > 15 cm of involvement beyond the anal verge
Who cannot join
- Women with a positive pregnancy test, who are breastfeeding, or who intend to become pregnant during the course of the study
- Diagnosis of Crohn's disease, microscopic colitis or indeterminate colitis
- Presence of ileostomy or colostomy, or history of prior colon resection
- Patients with planned hospitalization or surgery during the course of the study
- Known allergy to milk proteins, red meat or cornstarch
- Stools positive for enteric infection, including parasitic, or C. difficile toxin within 28 days of screening
Show all 11Show fewer
- Documented presence of Hetatitis B (HBsAg), Hepatitis C (HCV), or HIV
- Presence of dysplasia of any grade on colonoscopic biopsies
- Treatment for cancer (excluding non-melanomatous cancer of the skin or cervical carcinoma in situ) or lymphoproliferative disorder (including lymphoma) within 5 years
- History of tuberculosis (TB) or Listeria infection, or known exposure to another person with active TB disease within 12 weeks of screening; or history of past or current infection with different opportunistic infections
- History of TNF inhibitor (infliximab, adalimumab or certolizumab pegol) use with primary treatment failure. Secondary treatment failures due to intolerance, allergic reaction, or loss of response will not constitute a basis for exclusion. Oral immunosuppressives, mesalamine, and corticosteroids (up to 20mg of prednisone per day) will be permitted so long as these medications are stable for defined periods of time before study participation commences.
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
United States9 sites
Anaheim Clinical Trials
Anaheim, California, 92801
Clinical Research Institute of Michigan
Chesterfield, Michigan, 48047
Chevy Chase Clinical Research
Chevy Chase, Maryland, 20815
Remington-Davis, Inc.
Columbus, Ohio, 43215
Rocky Mountain Gastroenterology Associates
Lakewood, Colorado, 80215
Center for Digestive and Liver Disease
Mexico, Missouri, 65265
Nashville Medical Research Institute
Nashville, Tennessee, 37205
Oklahoma Foundation for Digestive Research
Oklahoma City, Oklahoma, 73104
Shafran Gastroenterology Center
Winter Park, Florida, 327789
Hungary3 sites
Semmelweis Egyetem
Budapest, 1083
Debreceni Egyetem Orvos- és Egészségtudományi Centrum
Debrecen, 4032
Kenézy Kórház Rendelöintézet Egészségügyi Szolgáltató Kft.
Debrecen, 4043
Canada2 sites
The Northern Alberta Clinical Trials and Research Centre
Edmonton, Alberta, T6G 2C8
Toronto Digestive Disease Associates
Toronto, Ontario, L4L 4Y7
About this study
Official title: A Multicenter, Double-Blind, Placebo-Controlled, Ascending-Dose, Repeat-Dose Safety and Pharmacokinetic Investigation of a Delayed-Release, Enteric-Coated Capsule Formulation of AVX 470 [Anti-TNF (Tumor Necrosis Factor) Globulin (Bovine)] in Patients With Active Ulcerative Colitis
The purpose of this study is to evaluate the safety and tolerability as well as the pharmacodynamic effects of multiple doses of AVX-470 administered orally in patients with active ulcerative colitis.
Read the detailed description
There is a significant unmet medical need for effective oral pharmacologic therapies for inflammatory bowel diseases such as ulcerative colitis. Current anti-TNF therapies, including infliximab and adalimumab, are effective treatments for these conditions, but they must be administered by intravenous or subcutaneous injection. The major safety concerns associated with the use of injectable anti-TNF therapies are infection, demyelinating disease, and lymphoma, all of which are the result of systemic exposure. These uncommon but serious side effects have limited the use of systemic anti-TNF antibody therapy to patients with severe disease that have failed to respond to first-line treatments.
AVX-470 is purified immunoglobulin (Ig) from the colostrum (early milk) of cows immunized with recombinant human tumor necrosis factor (rhTNF). AVX-470 is formulated in delayed-release enteric-coated capsules designed to protect the capsule contents from gastric acids following oral administration and to provide localized delivery to sites of inflammation in the distal intestine. Prior clinical experience with bovine Ig therapies in other human diseases suggests that AVX-470 will not be absorbed to any significant extent, meaning that systemic exposure could be minimized. The development of oral anti-TNF therapy targeting local intestinal disease activity might reduce the risks associated with injectable anti-TNF therapy and allow the convenience of oral dosing.
The present study is a first-in-human, Phase 1 clinical study. It is primarily intended to evaluate the safety and tolerability of multiple doses of AVX-470 administered orally to patients with active ulcerative colitis.
Animal models of ulcerative colitis using a mouse-specific TNF antibody derived from bovine colostrum demonstrated a 50% or more reduction in tissue TNF, TNF-messenger ribonucleic acid (mRNA), interleukin (IL)-6 mRNA, and myeloperoxidase and lowering of colonic inflammatory activity. Twenty-eight-day toxicology studies demonstrated no clinical or histologic findings in exposures above the intended clinical dose range.
- Conditions
- Ulcerative Colitis
- Being tested
- AVX 470, Placebo
- Keywords
- Ulcerative colitis
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVX 470Drug
active comparator
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| AVX 470 | Active comparator | AVX 470 0.2 g(Cohort 1), 1.6 g (Cohort 2) and 3.5 g (Cohort 3) will be administered daily for 28 days Receives: Drug: AVX 470 |
| Placebo | Placebo comparator | Placebo will be administered daily for 28 days as a comparator with AVX-470 (all dose groups) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of AVX-470 over 28 days of treatment
Assessments weekly during treatment and 1 week post treatment
Measured: 5 weeks
Secondary outcomes (2)
Pharmacokinetics (serum, stool and gastrointestinal mucosal tissue levels) of AVX-470
Measured: 4 weeks
Measure the induction of or change in a human anti-bovine immunoglobulin antibody (HABA) response to AVX 470
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Avaxia Biologics, Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Harris, MD, Study director, Avaxia Biologics, Incorporated
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01759056
- Sponsor's protocol ID
- AB1101
- Other IDs
- 2012-004850-27
- Status last verified
- Feb 2014
- First submitted
- 24 Dec 2012
- Last updated
- 5 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Harris MS, Hartman D, Lemos BR, Erlich EC, Spence S, Kennedy S, Ptak T, Pruitt R, Vermeire S, Fox BS. AVX-470, an Orally Delivered Anti-Tumour Necrosis Factor Antibody for Treatment of Active Ulcerative Colitis: Results of a First-in-Human Trial. J Crohns Colitis. 2016 Jun;10(6):631-40. doi: 10.1093/ecco-jcc/jjw036. Epub 2016 Jan 28.
PubMed 26822613Hartman DS, Tracey DE, Lemos BR, Erlich EC, Burton RE, Keane DM, Patel R, Kim S, Bhol KC, Harris MS, Fox BS. Effects of AVX-470, an Oral, Locally Acting Anti-Tumour Necrosis Factor Antibody, on Tissue Biomarkers in Patients with Active Ulcerative Colitis. J Crohns Colitis. 2016 Jun;10(6):641-9. doi: 10.1093/ecco-jcc/jjw026. Epub 2016 Jan 22.
PubMed 26802087
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double-Blind, Placebo-Controlled, Ascending-Dose, Repeat-Dose Safety and Pharmacokinetic Investigation of a Delayed-Release, Enteric-Coated Capsule Formulation of AVX 470 [Anti-TNF (Tumor Necrosis Factor) Globulin (Bovine)] in Patients With Active Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT01759056
- Acronym / sponsor ID
- AB1101
- Conditions
- Ulcerative Colitis
- Keywords
- Ulcerative colitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Avaxia Biologics, IncorporatedIndustry (pharma, biotech, devices)
- Study start
- Feb 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 2 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability as well as the pharmacodynamic effects of multiple doses of AVX-470 administered orally in patients with active ulcerative colitis.
Detailed description
There is a significant unmet medical need for effective oral pharmacologic therapies for inflammatory bowel diseases such as ulcerative colitis. Current anti-TNF therapies, including infliximab and adalimumab, are effective treatments for these conditions, but they must be administered by intravenous or subcutaneous injection. The major safety concerns associated with the use of injectable anti-TNF therapies are infection, demyelinating disease, and lymphoma, all of which are the result of systemic exposure. These uncommon but serious side effects have limited the use of systemic anti-TNF antibody therapy to patients with severe disease that have failed to respond to first-line treatments.
AVX-470 is purified immunoglobulin (Ig) from the colostrum (early milk) of cows immunized with recombinant human tumor necrosis factor (rhTNF). AVX-470 is formulated in delayed-release enteric-coated capsules designed to protect the capsule contents from gastric acids following oral administration and to provide localized delivery to sites of inflammation in the distal intestine. Prior clinical experience with bovine Ig therapies in other human diseases suggests that AVX-470 will not be absorbed to any significant extent, meaning that systemic exposure could be minimized. The development of oral anti-TNF therapy targeting local intestinal disease activity might reduce the risks associated with injectable anti-TNF therapy and allow the convenience of oral dosing.
The present study is a first-in-human, Phase 1 clinical study. It is primarily intended to evaluate the safety and tolerability of multiple doses of AVX-470 administered orally to patients with active ulcerative colitis.
Animal models of ulcerative colitis using a mouse-specific TNF antibody derived from bovine colostrum demonstrated a 50% or more reduction in tissue TNF, TNF-messenger ribonucleic acid (mRNA), interleukin (IL)-6 mRNA, and myeloperoxidase and lowering of colonic inflammatory activity. Twenty-eight-day toxicology studies demonstrated no clinical or histologic findings in exposures above the intended clinical dose range.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AVX 470 | Active comparator | Drug: AVX 470AVX 470 0.2 g(Cohort 1), 1.6 g (Cohort 2) and 3.5 g (Cohort 3) will be administered daily for 28 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo will be administered daily for 28 days as a comparator with AVX-470 (all dose groups) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Men or women aged 18 75, inclusive
- Established diagnosis of ulcerative colitis involving the sigmoid colon or proximal segments of bowel
- Total Mayo score between 5-12, inclusive, with endoscopic subscore of the Mayo score ≥ 2 and > 15 cm of involvement beyond the anal verge
Key exclusion criteria (11 listed)
- Women with a positive pregnancy test, who are breastfeeding, or who intend to become pregnant during the course of the study
- Diagnosis of Crohn's disease, microscopic colitis or indeterminate colitis
- Presence of ileostomy or colostomy, or history of prior colon resection
- Patients with planned hospitalization or surgery during the course of the study
- Known allergy to milk proteins, red meat or cornstarch
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AVX 470active comparator | Drug | AVX 470 |
| Placebo | Drug | Placebo |
Primary outcome
Safety and tolerability of AVX-470 over 28 days of treatment
Time frame: 5 weeks
Assessments weekly during treatment and 1 week post treatment
2 secondary outcomes
Pharmacokinetics (serum, stool and gastrointestinal mucosal tissue levels) of AVX-470
Time frame: 4 weeks
Measure the induction of or change in a human anti-bovine immunoglobulin antibody (HABA) response to AVX 470
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2014.
- Derived from this study: PubMed 26822613Harris MS, Hartman D, Lemos BR, Erlich EC, Spence S, Kennedy S, Ptak T, Pruitt R, Vermeire S, Fox BS. AVX-470, an Orally Delivered Anti-Tumour Necrosis Factor Antibody for Treatment of Active Ulcerative Colitis: Results of a First-in-Human Trial. J Crohns Colitis. 2016 Jun;10(6):631-40. doi: 10.1093/ecco-jcc/jjw036. Epub 2016 Jan 28.
- Derived from this study: PubMed 26802087Hartman DS, Tracey DE, Lemos BR, Erlich EC, Burton RE, Keane DM, Patel R, Kim S, Bhol KC, Harris MS, Fox BS. Effects of AVX-470, an Oral, Locally Acting Anti-Tumour Necrosis Factor Antibody, on Tissue Biomarkers in Patients with Active Ulcerative Colitis. J Crohns Colitis. 2016 Jun;10(6):641-9. doi: 10.1093/ecco-jcc/jjw026. Epub 2016 Jan 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Harris, MD study director
Avaxia Biologics, Incorporated
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AVX 470 in people with Ulcerative Colitis, run by Avaxia Biologics, Incorporated at 16 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Hungary, Belgium, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of AVX-470 over 28 days of treatment (time frame: 5 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01759056, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2014.