CRD3003 - IMUNITI

Principal Investigator: Kathryn Peterson
Keywords: CNTO1275CRD3003: A phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety and efficacy of Ustekinumab maintenance therapy in subjects with moderately to severely active crohn's disease. Department: Gastroenterology
IRB Number: 00051235 Co Investigator: Kathleen Boynton
Specialty: Gastroenterology
Sub Specialties: Irritable Bowel Syndrome
Recruitment Status: Active, not recruiting

Contact Information

Shannah Aleiwe
shannah.aleiwe@hsc.utah.edu
801-587-9050

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel-group multicenter study of the safety and efficacy of SC regimens of ustekinumab in maintaining disease control through Week 44 in subjects with moderately to severely active Crohn’s disease induced into clinical response with ustekinumab in the induction studies, CNTO1275CRD3001 or CNTO1275CRD3002. The maintenance portion of the study continues to Week 44 and the subsequent study extension will continue up to Week 272. The number of subjects enrolling in this study will be dependent on the number of subjects from the induction studies eligible to enroll into the maintenance study.

In summary, there is a significant medical need for new safe and effective therapies for moderate to severe, active Crohn’s disease, particularly in patients who have failed to respond to TNF antagonists. Inhibiting IL-12 and IL-23 and their associated inflammatory pathways via

blockade of the shared IL-12 p40 subunit by ustekinumab constitutes a novel mechanism of

action with substantial preclinical rationale as well as recent clinical data supporting that it is a

promising therapeutic approach for Crohn’s disease patients.

 

OBJECTIVES

Primary Objectives

The primary objectives are:

· To evaluate the efficacy of IV induction regimens of ustekinumab in inducing clinical

response in subjects with moderately to severely active Crohn’s disease.

· To evaluate the safety of IV induction regimens of ustekinumab in subjects with moderately

to severely active Crohn’s disease.

 

Secondary Objectives

The secondary objectives are:

· To evaluate the efficacy of IV induction regimens of ustekinumab in inducing clinical remission.

· To evaluate the efficacy of IV induction regimens of ustekinumab in improving disease specific

health-related quality of life.

· To evaluate the pharmacokinetics and pharmacodynamics of ustekinumab therapy, including

changes in CRP, fecal calprotectin, fecal lactoferrin, and other pharmacodynamic biomarkers.

· To provide, along with induction study CNTO1275CRD3001, the target study population to

be evaluated in the maintenance study CNTO1275CRD3003.

Inclusion Criteria

Each potential subject must satisfy all of the following criteria to be enrolled in the study. Each subject must:
 

 
1. Have received study agent at Week 0 in study CNTO1275CRD3001 or CNTO1275CRD3002 and completed the Week 8 CDAI score evaluation.
 
2. Be able to complete the Week 0 visit in study CNTO1275CRD3003 within 4 days of the Week 8 visit in study CNTO1275CRD3001 or CNTO1275CRD3002. At the discretion of the investigator, the window may be extended to 8 days to allow appropriate treatment and/or recovery of nonserious infections (eg, acute upper respiratory tract infection, simple urinary tract infection).
 
3. Be able and willing to adhere to the study visit schedule and comply with other protocol requirements
 
4. Be capable of providing informed consent, which must be obtained prior to any study-related procedures
 

 

 

 

 

 

 

Exclusion Criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study. The subject will be excluded if he or she:
 

 
1. Had any of the following changes to their concomitant medications due to Crohn’s disease (ie, lack of efficacy) since Week 0 of studies CNTO1275CRD3001 and CNTO1275CRD3002
 
a. Increase in physician-prescribed daily dose of oral corticosteroids of more than 5 mg or more of prednisone (or equivalent increase in prednisone-equivalent dose of other
 
corticosteroids),
 
b. Initiation of oral budesonide or increase in daily dose
 
c. Initiation of parenteral, and oral corticosteroids for Crohn’s disease, except for dose equivalent substitutions among oral corticosteroids
 
d. Initiation or increased physician-prescribed daily dose of methotrexate (MTX), 6-MP, or azathioprine (AZA), except for dose equivalent substitutions
 
2. Initiated a protocol prohibited medication since Week 0 of studies CNTO1275CRD3001 and CNTO1275CRD3002:
 
a. Immune suppressing Immunomodulatory agents other than 6-MP/AZA or MTX (including but not limited to 6-TG, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, tofacitinib and other Janus kinase [JAK] inhibitors)
 
b. Immunosuppressant biologic agents (including but not limited to TNF-antagonists, natalizumab, abatacept, commercial ustekinumab)
 
c. Experimental Crohn’s disease medications (including but not limited to thalidomide,briakinumab, vedolizumab, traficet, AMG-827)
 
3. Underwent a Crohn’s disease related surgery since Week 0 of induction study CNTO1275CRD3001 or CNTO1275CRD3002. Seton placement and recent cutaneous and perianal abscesses which have been drained and adequately treated at least 3 weeks prior to receiving baseline study agent are not exclusionary provided that there is no anticipated need for any further surgery
 
4. Subjects from countries with high multidrug-resistant TB burden (eg, South Africa,Bulgaria, and the Russian Federation) diagnosed with latent TB during induction study CNTO1275CRD3001 or CNTO1275CRD3002, or any subject who has discontinued or is
 
noncompliant with appropriate therapy for the treatment of latent TB.
 
5. Are diagnosed with any medical condition (or signs or symptoms thereof) which would have precluded enrollment in induction studies CNTO1275CRD3001 and CNTO1275CRD3002. This includes any lymphoproliferative disorder or malignancy (other than basal cell carcinoma of the skin), opportunistic or other significant infection,
 
or other severe, progressive, or uncontrolled medical (eg renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, or autoimmune) or psychiatric disease, including recent significant instability in a previous condition.
 
6. Have signs and symptoms of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis.
 
7. Is a woman who is pregnant, or breast-feeding, or planning to become pregnant or is a man who plans to father a child while enrolled in this study or within 20 weeks after the last dose of study agent.