Crohn's DiseasePhase 1NCT00007163
Monoclonal Antibody Treatment of Crohn's Disease
A Phase 1 study testing J695 in people with Crohn's Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of an experimental drug called J695 for treating patients with Crohn's disease-a long-term recurring inflammation of the small and large intestine. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- J695
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2000to Nov 2002
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All subjects must have a verifiable diagnosis of Crohn's disease of at least 4 months' duration. The diagnosis must be supported by characteristic 1) clinical features (symptomatic or endoscopic) or radiographic findings and 2) histopathologic changes.
- All subjects must be over age 18.
- Subjects must be male or female who are surgically sterile (hysterectomy and/or bilateral oophorectomy), have a history of tubal ligation, or are post-menopausal with greater than or equal to 12 months duration of spontaneous amenorrhea.
- Subjects are eligible if the Crohn's disease is mildly to moderately active based on a Crohn's Disease Activity Index score between 220 and 450 (with a diarrhea rating or abdominal pain rating greater than or equal to 25).
- If currently receiving any medications for Crohn's disease, subjects may only be on a stable regimen of one or a combination of the following drug doses and durations:
- Antibiotic therapy greater than or equal to 2 weeks,
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- Corticosteroids (less than or equal to 20 mg Prednisone/d, or Prednisone equivalent) greater than or equal to 4 weeks,
- 5-ASA/Sulfasalazine greater than or equal to 4 weeks,
- Azathioprine/6-MP greater than or equal to 8 weeks,
- (Note: patients receiving azathioprine or 6-MP must have been receiving these medications for greater than or equal to 12 weeks before randomization).
- Use of prophylactic methods of birth control throughout the study period for male and female subjects who are not surgically sterile or postmenopausal: abstinence or barrier methods for male subjects, use of additional form of contraception (abstinence, barrier or hormal method) for women of child-bearing potential with a history of tubal ligation, and use of two forms of contraception for women of child-bearing potential who had been enrolled in this study prior to knowledge of the developmental toxicity data in monkeys.
- Women of child-bearing potential (women who are not surgically sterile or postmenopausal) must have a negative serum Beta-hCG to exclude early pregnancy.
- Subjects must have negative results on stool examination for culture of enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. coli O157/H7), Clostridia difficile toxin assay, enteric parasites and their ova (including Cryptosporidia).
- Subjects must have a chest X-ray free of changes consistent with any infections or malignancy.
- Subjects who cannot meet the above requirements are excluded.
- Subjects using any of the following medications within the specified time period prior to the first dose of study drug or at any time during the study are excluded:
- NSAIDs/COX-2 inhibitors/ greater than 500 mg/d aspirin within 24 hours,
- Corticosteroid enema or 5-ASA enema or suppositories within 7 days,
- Corticosteroids (greater than 20 mg Prednisone/d or Prednisone equivalent) within 4 weeks,
- Methotrexate, Cyclosporin, Tacrolimus (FK506), Thalidomide, Etanercept (Enbrel), Mycophenolate mofetil (CellCept), or any biological therapy,
- Monoclonal antibodies to TNF within 4 months,
- Any experimental agent within 1 month.
- Subjects with multiple bowel resections (greater than or equal to 200 cm) AND enteral or parenteral therapy to maintain weight are excluded.
- Subjects with use of any other investigational agent within 30 days of randomization for this study are excluded.
- Subjects must not have any of the following abnormalities on an electrocardiogram: QT(c) greater than 0.48 sec, Mobitz type II second or third degree atrioventricular block, left bundle branch block or right bundle branch block with any fascicular block, changes consistent with acute ischemia.
- Subjects with moderate persistent asthma defined as the presence of one of these features are excluded:
- Clinical features before treatment: Daily symptoms, exacerbations affect activity and sleep, nighttime asthma symptoms greater than 1 time a week, peak expiratory flow (PEF) or forced expiratory volume (FEV1) greater than 60% to less then 80% of predicted, variability greater than 30%;
- Daily medication required to maintain control: Daily controller medications (especially for nighttime symptoms): inhaled corticosteroids or long-acting bronchodilators.
- Subjects with severe persistent asthma defined as the presence of one of the features listed below are excluded:
- Clinical features before treatment: Continuous symptoms, frequent exacerbations, frequent nighttime asthma symptoms, physical activities limited by asthma symptoms, PEF or FEV(1) less than 60% predicted, variability greater than 30%;
- Daily medication required to maintain control: Multiple daily controller medications (long-term): high-dose inhaled corticosteroids, long-acting bronchodilators and oral corticosteroids.
Who cannot join
- Subjects with a history of tuberculosis or BCG vaccination are excluded.
- Subjects with a diagnosis of ulcerative colitis are excluded.
- Subjects with Cushing's syndrome are excluded.
- Subjects with a current ileostomy or colostomy are excluded.
- Subjects with current active bowel obstruction, intestinal perforation, significant GI hemorrhage, or known presence of high grade stricture are excluded.
- Subjects with HIV positivity or signs and symptoms consistent with HIV infection are excluded.
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- Subjects with acute systemic or intestinal infection requiring antibiotics are excluded.
- Subjects with active hepatitis B or C are excluded.
- Subjects with decompensated liver disease (Childs-Pugh class B or C) are excluded.
- Subjects with any of the following are excluded:
- Hematocrit less than 30%,
- Platelet count greater than 700,000,
- Serum creatinine or BUN greater than 1.5 times the upper limit of normal,
- ALT (SGPT) or AST (SGOT) greater than 2 times the upper limit of normal,
- Total bilirubin greater than 1.25 times the upper limit of normal,
- Alkaline phosphatase greater than 1.5 times the upper limit of normal.
- Pregnant or nursing women are excluded.
- Subjects with a history of cancer (other than resected cutaneous basal or squamous cell carcinoma; and in situ cervical cancer) with less than 5 years documentation of a disease-free state are excluded.
- Subjects with a history of myocardial infarction within the last 12 months are excluded.
- Subjects expected to require surgery for their Crohn's disease within 12 weeks of study entry are excluded.
- Subjects with a condition that, in the investigator's opinion, places the patient at undue risk by participating in the study are excluded.
- Subjects with a history of anaphylactic reaction to anti-TNF alpha therapy are excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Safety Study of Two Parallel Dose Levels of Subcutaneously Administered Human Monoclonal Antibody to Interleukin-12 (J695) in Patients With Active Crohn's Disease
This study will examine the safety and effectiveness of an experimental drug called J695 for treating patients with Crohn's disease-a long-term recurring inflammation of the small and large intestine. This disease is currently treated with steroids, sulfasalazine (Azulfidine), 5-ASA drugs (Pentasa, Asacol), immune suppressants, antibiotics, and an antibody against TNF-alpha. Despite the number and variety of available therapies for Crohn's disease, many patients do not respond adequately to treatment or they develop severe side effects from the medicines. Therefore, new treatments must be developed. J695 is an antibody that is identical to a human antibody but chemically changed so that it can attach to and eliminate an inflammatory chemical made by the body called interleukin-12 (IL-12). Animal studies have shown that eliminating IL-12 with an antibody can prevent inflammation in the gut and can also heal inflammation that has already developed.
Patients 18 years of age and older who have had Crohn's disease for at least 4 months may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, chest X-ray, blood and urine tests, stool analysis and possibly a review of medical records. They will complete a Crohn's Disease Activity Index Questionnaire for 7 days. Participants will be randomly assigned to one of two treatment groups, as follows:
Read more
Group 1
Patients in this group will receive an injection of either J695 or placebo (a solution that does not contain any active medicine) under the skin on day 1 of the study, on day 29, and then weekly for a total of seven injections. After the last injection, patients will be followed for an additional 18 weeks. They will be monitored periodically throughout the study with physical examinations, disease activity index scores, and blood and urine tests.
Group 2
Patients in group 2 will receive an injection of J695 or placebo on day 1 of the study and then weekly for a total of six injections. They will be followed for an additional 18 weeks. Patients will be monitored as described above for group 1.
Participants may be asked to undergo additional tests as part of a sub-study in this protocol. These include colonoscopies to examine changes in inflammation in the gut and blood tests to analyze changes in the cells and body chemicals that affect the inflammation.
Read the detailed description
The purpose of this study is to evaluate the safety of and the clinical response to a human monoclonal anti-interleukin-12 antibody (J695) administered to patients with Crohn's disease. Crohn's disease, an incurable, chronic, relapsing inflammation of the small and large intestine, affects approximately 500,000 people in the United States. The disease is characterized by full-thickness involvement of the gut wall leading to episodes of abdominal pain, diarrhea, hematochezia, weight loss and complications such as bowel obstruction, fistula formation and extraintestinal manifestations. The rationale for this study is based on two compelling observations. First, despite the standard therapeutic use of steroids, aminosalicylates, antibiotics, antimetabolite immunosuppressants (6-MP, methotrexate), and early agents of the emerging biologics class of drugs (anti-TNF alpha antibodies, e.g.), the treatment of Crohn's disease is still troubled by loss of effectiveness of standard therapy over time, outright nonresponsiveness, and serious medication side effects. For these reasons newer agents for the treatment of Crohn's disease need to be developed and tested. Second, studies in both animals and humans support a central role for IL-12 in the gut inflammatory response in Crohn's disease. Administration of anti-IL-12 antibodies in animal models has prevented inducible or ameliorated established colitis. For these reasons IL-12 is an appropriate therapeutic target for the treatment of Crohn's disease.
This study proposes to measure the toxicity and clinical effect of two doses of anti-IL-12 (J695) administered subcutaneously to patients with moderately active Crohn's disease. The primary outcome measure is the rate and severity of adverse events. Secondary outcome measures include J695 pharmacodynamics, incidence of anti-J695 antibodies, and clinical response. A separate substudy at the NIH will measure gut lymphocyte apoptosis and gut and peripheral blood cytokine responses to study drug as well as endoscopic and histologic response to treatment. Our short-term goal is to assure good tolerance of anti-IL-12 treatment regimens in Crohn's disease patients and observe a beneficial clinical response. The long-term goal of this study is to establish anti-IL-12 as an effective alternative with a low risk profile in the therapeutic armamentarium for Crohn's disease.
- Conditions
- Crohn's Disease
- Being tested
- J695
- Keywords
- Immunosuppression, Recombinant IgG1, Apoptosis, Interferon Gamma, Colonoscopy, Crohn's Disease, Immunotherapy, IL-12
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
J695Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2000 (estimated)
- Study startDec 2000
- Study completionNov 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Enrolment
- 40 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00007163
- Sponsor's protocol ID
- 010040
- Other IDs
- 01-I-0040
- Status last verified
- Nov 2002
- First submitted
- 9 Dec 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Blumberg RS, Saubermann LJ, Strober W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol. 1999 Dec;11(6):648-56. doi: 10.1016/s0952-7915(99)00032-1.
PubMed 10631550Monteleone G, Biancone L, Marasco R, Morrone G, Marasco O, Luzza F, Pallone F. Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology. 1997 Apr;112(4):1169-78. doi: 10.1016/s0016-5085(97)70128-8.
PubMed 9098000Fais S, Capobianchi MR, Silvestri M, Mercuri F, Pallone F, Dianzani F. Interferon expression in Crohn's disease patients: increased interferon-gamma and -alpha mRNA in the intestinal lamina propria mononuclear cells. J Interferon Res. 1994 Oct;14(5):235-8. doi: 10.1089/jir.1994.14.235.
PubMed 7861027
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Safety Study of Two Parallel Dose Levels of Subcutaneously Administered Human Monoclonal Antibody to Interleukin-12 (J695) in Patients With Active Crohn's Disease
- ClinicalTrials.gov ID
- NCT00007163
- Acronym / sponsor ID
- 010040
- Conditions
- Crohn's Disease
- Keywords
- Immunosuppression, Recombinant IgG1, Apoptosis, Interferon Gamma, Colonoscopy, Crohn's Disease, Immunotherapy, IL-12
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Dec 2000
- Study completion
- Nov 2002
- First posted
- 11 Dec 2000 (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.
This study will examine the safety and effectiveness of an experimental drug called J695 for treating patients with Crohn's disease-a long-term recurring inflammation of the small and large intestine. This disease is currently treated with steroids, sulfasalazine (Azulfidine), 5-ASA drugs (Pentasa, Asacol), immune suppressants, antibiotics, and an antibody against TNF-alpha. Despite the number and variety of available therapies for Crohn's disease, many patients do not respond adequately to treatment or they develop severe side effects from the medicines. Therefore, new treatments must be developed. J695 is an antibody that is identical to a human antibody but chemically changed so that it can attach to and eliminate an inflammatory chemical made by the body called interleukin-12 (IL-12). Animal studies have shown that eliminating IL-12 with an antibody can prevent inflammation in the gut and can also heal inflammation that has already developed.
Patients 18 years of age and older who have had Crohn's disease for at least 4 months may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, chest X-ray, blood and urine tests, stool analysis and possibly a review of medical records. They will complete a Crohn's Disease Activity Index Questionnaire for 7 days. Participants will be randomly assigned to one of two treatment groups, as follows:
Group 1
Patients in this group will receive an injection of either J695 or placebo (a solution that does not contain any active medicine) under the skin on day 1 of the study, on day 29, and then weekly for a total of seven injections. After the last injection, patients will be followed for an additional 18 weeks. They will be monitored periodically throughout the study with physical examinations, disease activity index scores, and blood and urine tests.
Group 2
Patients in group 2 will receive an injection of J695 or placebo on day 1 of the study and then weekly for a total of six injections. They will be followed for an additional 18 weeks. Patients will be monitored as described above for group 1.
Participants may be asked to undergo additional tests as part of a sub-study in this protocol. These include colonoscopies to examine changes in inflammation in the gut and blood tests to analyze changes in the cells and body chemicals that affect the inflammation.
Detailed description
The purpose of this study is to evaluate the safety of and the clinical response to a human monoclonal anti-interleukin-12 antibody (J695) administered to patients with Crohn's disease. Crohn's disease, an incurable, chronic, relapsing inflammation of the small and large intestine, affects approximately 500,000 people in the United States. The disease is characterized by full-thickness involvement of the gut wall leading to episodes of abdominal pain, diarrhea, hematochezia, weight loss and complications such as bowel obstruction, fistula formation and extraintestinal manifestations. The rationale for this study is based on two compelling observations. First, despite the standard therapeutic use of steroids, aminosalicylates, antibiotics, antimetabolite immunosuppressants (6-MP, methotrexate), and early agents of the emerging biologics class of drugs (anti-TNF alpha antibodies, e.g.), the treatment of Crohn's disease is still troubled by loss of effectiveness of standard therapy over time, outright nonresponsiveness, and serious medication side effects. For these reasons newer agents for the treatment of Crohn's disease need to be developed and tested. Second, studies in both animals and humans support a central role for IL-12 in the gut inflammatory response in Crohn's disease. Administration of anti-IL-12 antibodies in animal models has prevented inducible or ameliorated established colitis. For these reasons IL-12 is an appropriate therapeutic target for the treatment of Crohn's disease.
This study proposes to measure the toxicity and clinical effect of two doses of anti-IL-12 (J695) administered subcutaneously to patients with moderately active Crohn's disease. The primary outcome measure is the rate and severity of adverse events. Secondary outcome measures include J695 pharmacodynamics, incidence of anti-J695 antibodies, and clinical response. A separate substudy at the NIH will measure gut lymphocyte apoptosis and gut and peripheral blood cytokine responses to study drug as well as endoscopic and histologic response to treatment. Our short-term goal is to assure good tolerance of anti-IL-12 treatment regimens in Crohn's disease patients and observe a beneficial clinical response. The long-term goal of this study is to establish anti-IL-12 as an effective alternative with a low risk profile in the therapeutic armamentarium for Crohn's disease.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (31 listed)
- All subjects must have a verifiable diagnosis of Crohn's disease of at least 4 months' duration. The diagnosis must be supported by characteristic 1) clinical features (symptomatic or endoscopic) or radiographic findings and 2) histopathologic changes.
- All subjects must be over age 18.
- Subjects must be male or female who are surgically sterile (hysterectomy and/or bilateral oophorectomy), have a history of tubal ligation, or are post-menopausal with greater than or equal to 12 months duration of spontaneous amenorrhea.
- Subjects are eligible if the Crohn's disease is mildly to moderately active based on a Crohn's Disease Activity Index score between 220 and 450 (with a diarrhea rating or abdominal pain rating greater than or equal to 25).
- If currently receiving any medications for Crohn's disease, subjects may only be on a stable regimen of one or a combination of the following drug doses and durations:
Key exclusion criteria (22 listed)
- Subjects with a history of tuberculosis or BCG vaccination are excluded.
- Subjects with a diagnosis of ulcerative colitis are excluded.
- Subjects with Cushing's syndrome are excluded.
- Subjects with a current ileostomy or colostomy are excluded.
- Subjects with current active bowel obstruction, intestinal perforation, significant GI hemorrhage, or known presence of high grade stricture are excluded.
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 |
|---|---|---|
| J695 | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 10631550Blumberg RS, Saubermann LJ, Strober W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol. 1999 Dec;11(6):648-56. doi: 10.1016/s0952-7915(99)00032-1.
- Background: PubMed 9098000Monteleone G, Biancone L, Marasco R, Morrone G, Marasco O, Luzza F, Pallone F. Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology. 1997 Apr;112(4):1169-78. doi: 10.1016/s0016-5085(97)70128-8.
- Background: PubMed 7861027Fais S, Capobianchi MR, Silvestri M, Mercuri F, Pallone F, Dianzani F. Interferon expression in Crohn's disease patients: increased interferon-gamma and -alpha mRNA in the intestinal lamina propria mononuclear cells. J Interferon Res. 1994 Oct;14(5):235-8. doi: 10.1089/jir.1994.14.235.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing J695 in people with Crohn's Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 31 inclusion and 22 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 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00007163, which also lists 3 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 4 Mar 2008.