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Clinical Trials

A Study of The Safety and Effictiveness of CNTO 148 (Golimumab) in Patients with Moderately to Severely Active Ulcerative Colitis

Summary:   The purpose of this clinical study is to assess the effects (good and bad) of CNTO 148 (golimumab) therapy in patients with Ulcerative Colitis.

HR#: 17852
PRINCIPAL INVESTIGATOR: Lawrence Comerford, , MD, MS
SPONSOR: Centocor
TARGET ENROLLMENT: 6
DISEASE TYPE: Ulcerative Colitis
BODY LOCATION(S): Large Intestine,
PRIMARY OBJECTIVE: 1. To evaluate the efficacy of IV induction regimens of golimumab in unducing clinical ersponse in subjects with moderately to severely active UC. 2. To evaluate the safety of IV induction regimens of golimumab in subjects with moderately to severely active UC.
SECONDARY OBJECTIVE(S): 1. To evaluate the efficacy of IV induction regimens of golimumab in inducing in clinical remission. 2. To evaluate the efficacy of IV induction regimens of golimumab in inducing mucosal healing. 3. To evaluate the efficacy of IV induction regimens of golimumab in improving disease-specific health-related quality of life. 4. To provide the target study population to be evaluated in the 1-year golimumab maintenance study (C0524T18).
INCLUSION CRITERIA:
1 Are men or women 18 years of age or older.
2 Had UC diagnosed prior to screening.
3 Must either be currently receiving treatment with, or have a history of having failed to respond to, or tolerate, at least 1 of the following therapies: oral corticosteroids, 6-MP, or AZA.
4 Prior to the screening endoscopy of the subject's first entry in the Mayo diary cards, the following conditions must be met:a. if receiving 6-MP, AZA, or MTX, must have been receiving it for at least 12 weeks. The class of agent (6-MP/AZA versus MTX) prescribed may not have changed during those 12 weeks, and the dose must be stable for at least 4 weeks. b. If 6-MP, AZA, or MTX have been recently discontinued, they must have been stopped for at least 4 weeks.c. If receiving oral 5-ASA compounds or oral corticosteroids, the dose must have been stable for at least 2 weeks.d. If oral 5-ASA compounds or oral corticosteroids have been recently discontinued, they must have been stopped for at least 2 weeks.e. The following medications/therapies must have been discontinued for at least 2 weeks: 1. Rectal corticosteroids 2. Rectal 5-ASA compounds 3. Parenteral corticosteroids 4. Total parenteral nutrition (TPN) 5. Pentoxifylline 6. Thalidomide or related agents 7. Antibiotics for the treatment of UC (ie, ciprofloxacin, metronidazole, or rifaximin)
5 Must be ambulatory and have moderately to severely active UC confirmed during the screening endoscopy by a >=2 endoscopy subscore of the Mayo score.
6 Must have a diagnosis of UC confirmed by a biospy collected at the screening endoscopy procedure or have a previous biopsy result obtained within the last year that is consistent with the diagnosis of UC.
7 Have moderately to severely active UC, defined as a baseline (Week 0) Mayo score of 6 to 12, inclusive.
8 All subjects >= 45 years of age, must either have had a colonoscopy to assess for the presence of adenomatous polyps within 5 years of the first administration of study agent or a colonoscopy to assess for the presence of adenomatous polyps at the screening visit. The adenomatous polyps must be removed prior to the first administration of study agent.
9 All subjects who have had extensive colitis for >= 8 years, or disease limited to the left side of the colon for >= 10 years, must either have had a colonoscopy to assess the presence of dysplasia within 1 year prior to the first administration of study agent or a colonoscopy to assess the presence of malignancy at the screening visit.
10 The investigator has discussed with the subject the information contained within the informed consent regarding anti-TNF therapies and the potential risk of cancer, and has reviewed with the subject country-specific guidance (local practice) on cancer screening and the impact of life-style choices (eg, smoking) on the risk of developing cancer.
11 Are considered eligible according to the following TB screening criteria:a. Have no history of latent or active TB prior to screening.b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.c. Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent.d. Within 2 months prior to the first administration of study agent, either have negative diagnostic TB test results (defined as both a negative tuberculin skin test and a negative QuantiFERON-TB Gold test), or have a newly identified positive diagnostic TB test result (defined as either a positive tuberculin skin test or a positive QuantiFERON-TB Gold test) during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to our simultaneously with the first administration of study agent.e. Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.
12 Have negative stool results for enteric pathogens.
13 During the study and for 6 months after receiving the last administration of study agent, women of childbearing potential or men capable of fathering children must agree to use adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization). Women of childbearing potential must test negative for pregnancy at screening and at Week 0.
14 14. Have screening laboratory test results as follows: a. White blood cells >= 2.5x10^3 cells/uL (SI: >= 2.5x10^9 cells/L) b. Neutrophils >=1.5x10^3 cells/uL (SI: >=1.5x10^9 cells/L) c. Platelets >=100x10^3 cells/uL) (SI: >=100x10^9 cells/L) d. Serum creatinine <=1.5 mg/dL (SI: <=133 umol/L) e. Serum ALT and AST levels not exceeding 3.0 times the ULN for the central laboratory.
15 Must be able and willing to adhere to the study visit schedule and comply with other protocol requirements.
16 Are capable of providing informed consent, which must be obtained prior to any study-related procedures.
EXCLUSION CRITERIA:
1 Have severe extensive colitis as evidenced by: a. Investigator judgement that the subject is likely to require a colectomy within 12 weeks of baseline OR b. Symptom complex at screening or baseline visits that includes at least 4 of the following: 1. diarrhea with >= 6 bowel movements/day with macroscopic blood in stool 2. focal severe or rebound abdominal tenderness 3. persistent fever (>= 37.5 C) 4. tachycardia (>90 beats/minute) 5. anemia (hemoglobin <8.5 g/dL)
2 Have UC limited to the rectum only or to <20cm of the colon.
3 Presence of a stoma.
4 Presence or history of a fistula.
5 Require, or required within the 2 months prior to screening, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from study agent treatment.
6 Presence of symptomatic colonic or small bowel obstruction, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy).
7 History of extensive colonic resection (eg, less than 30cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity.
8 History of colonic mucosal dysplasia.
9 Presence of screening endoscopy of adenomatous colonic polyps, if not removed prior to study entry, or history of adenomatous colonic polyps that were not removed.
10 Have ever received biologic therapy targeted at TNFa (eg, infliximab, etanercept, certolizumab, adalimumab).
11 Have ever received natalizumab or other agents that target alpha-4-integrin.
12 Have ever received agents that deplete B cells (eg, rituximab) or T cells (eg, alemtuzumab, visilizumab).
13 Are receiving oral corticosteroids at a dose of greater than 40mg of prednisone or its equivalent per day.
14 Have received cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 8 weeks prior to first administration of study agent.
15 Have a known hypersensitivity to human immunoglobulin proteins or other components of goliumumab.
16 Have used any investigational drug within 4 weeks prior to first administration of study agent or within 5 half-lives of the investigational agent, whichever is longer.
17 Have used apheresis (ie, Adacolumn apheresis) within 2 weeks prior to first administration of study agent.
18 Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.
19 Have a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (eg, recurrent pyelonephritis, chronic cystitis), an open, draining, or infected skin wound, or an ulcer.
20 Have immune deficiency syndrome (eg, severe combined immunodeficiency syndrome [SCIDS], T cell deficiency syndromes, B cell deficiency syndromes, and chronic granulomatous disease).
21 Have signs or symptoms of infection with HIV, hepatitis B or hepatitis C.
22 Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.
23 Have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to screening.
24 Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB.
25 Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months prior to the first administration of study agent, during the study, or within 6 months after the last administration of study agent.
26 Have had a serious infection (eg, hepatitis, pneumonia, or pyelonephritis), have been hospitalized for an infection, or have been treated with parenteral antibiotics for an infection within 2 months prior to the first administration of study agent. Less serious infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator.
27 Presence or history of any malignancy within 5 years of screening (with exception of nonmelanoma skin cancer that has been treated with no evidence of recurrence).
28 Presence or history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), or clinically significant hepatomegaly or splenomegaly.
29 Concomitant diagnosis or history of CHF, including medically controlled asymptomatic CHF.
30 Have signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, psychiatric, or cerebral diseases.
31 History of systemic lupus erythematosus.
32 Have a transplanted organ (with the exception of a corneal transplant performed > 3 months prior to first administration of study agent).
33 History of demyelinating disease, such as multiple sclerosis or optic neuritis.
34 Have or have had a substance abuse (drug or alcohol) problem within the previous 3 years.
35 Have poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period.
36 Are participating in another study with an investigational agent or procedure.
37 Are pregnant, nursing, or planning pregnancy (both men and women) within 6 months following the last administration of study agent.
TREATMENT GROUPS:
LENGTH OF STUDY:
CONTACTS:
  • Rebekah Whichard, , BA, CCRC (Primary Study Coordinator)
    (843) 876-7233 or richreb@musc.edu
  • Kyle Orrell, MSHP (DDC Research Program Manager)
    843-876-4303 or orrell@musc.edu
  • Lawrence Comerford, , MD, MS (Principal Investigator)
    (843) 876-4262 or comerfol@musc.edu