GA29145

Principal Investigator: John  Valentine
Keywords: Crohns , Etrolizumab Department: Gastroenterology
IRB Number: 00082117 Co Investigator:  
Specialty: Gastroenterology
Sub Specialties: Inflammatory Bowel Disease/Crohn's/Ulcerative Colitis
Recruitment Status: Recruiting

Contact Information

Julie Will
julie.will@hsc.utah.edu
801-587-9060

Brief Summary

Protocol GA29144: A Phase III, Randomized, Double-blind, Placebo-Controlled, Multicenter study to evaluate the efficacy and safety of Etrolizumab as an induction and maintenance treatment for patients with moderately to severely active Crohn's Disease has been submitted as a separate IRB application.  Please see IRB 80265. 
 
The objectives of this OLE-SM study are as follows:
Part 1 (OLE)
• To assess the long-term safety and efficacy of etrolizumab in patients eligible for Part 1 (OLE)
Part 2 (SM)
• PML safety monitoring in patients who have stopped study treatment
OTHER SAFETY OBJECTIVES
The other safety objectives for this study are as follows:
Part 1 (OLE)
• To evaluate the incidence, rate per subject-year, and severity of infection-related adverse events
• To evaluate the incidence and rate per subject-year of malignancies
• To evaluate the incidence and severity of hypersensitivity reactions
• To evaluate the incidence and the clinical significance of anti-therapeutic antibodies (ATAs)
 
2.3 EXPLORATORY OBJECTIVE OF THE STUDY
The exploratory objective for this study is as follows:
Part 1 (OLE)
• To assess endoscopic appearance at Week 108

Inclusion Criteria

  • Patients who were previously enrolled in Study GA29144 and experienced any of the following:

Disease worsening in the Induction Phase of Study GA29144, defined as both CDAI and PRO2 scores at Week 10 or later in the Induction Phase being greater than the patient’s baseline (Week 0) score

Not eligible for the Maintenance Phase in Study GA29144

A clinical relapse during the Maintenance Phase of Study GA29144, defined as ³ 100-point increase in CDAI score from the Week 14 CDAI score

or ³ baseline (Week 0) CDAI score on two consecutive visits (which may

include unscheduled visits), and a CDAI score ³ 220 points

Completed the Maintenance Phase including the Week 74 clinic visit in Study GA29144

  • Ability and willingness to provide written informed consent and comply with the requirements of the OLE-SM protocol.
  • For women who are not postmenopausal (at least 12 months of

non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or to use a highly effective method of contraception (e.g., combined oral contraceptive pill or transdermal patch, spermicide and barrier [condoms], intrauterine device, implants for contraception, injections for contraception [with prolonged release], hormonal vaginal device,

 

sterilization, or surgical tubal ligation) during the treatment period and for at least 24 weeks after the last dose of study drug (see Appendix 4).

Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

  • For men: agreement to remain abstinent or to use a condom, as well as not donate sperm, during the treatment period and for at least 24 weeks after the last dose of study drug

Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

 

PART 2 (SM)

  • Patients who participated in Study GA29144 and are not eligible or chose not to enroll in Part 1 (OLE)
  • Patients who participated in Part 1 (OLE) of this protocol
  • Ability and willingness to provide written informed consent and comply with the requirements of Part 2 (SM) of the OLE-SM protocol

 

All patients must have completed the 12-week safety follow-up prior to entering Part 2 (SM).

Exclusion Criteria

Part 1 (OLE)

  • Patients who leave Study GA29144 before Week 10
  • Patients who discontinue study drug in the Induction Phase of Study GA29144, except for those escaping between and including Weeks 10 and 14 due to disease worsening
  • Inability to comply with the study protocol, in the opinion of the investigator
  • Pregnancy or lactation
  • Patients who developed an anaphylactic/anaphylactoid or severe allergic reaction to study medication during Study GA29144
  • Patients who have an untreated or unresolved serious infection event
  • Patients who experienced a de novo or reactivated serious viral infection such as hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV during Study GA29144
  • Patients who developed life-threatening infections during Study GA29144
  • Patients who developed a malignancy (with the exception of local and resected basal or squamous cell carcinoma of the skin) or who develop adenocarcinoma in situ (AIS), high-grade squamous intraepithelial lesions (HSIL), or cervical
 

intraepithelial neoplasia (CIN) of Grade > 1 on cervical Pap smear or who develop colonic dysplasia during Study GA29144

  • Receipt of the following prohibited medications since commencement of Study GA29144:

Any investigational treatment, including investigational vaccines

Use of T or B cell depleting agents (e.g., rituximab, alemtuzumab, or visilizumab), with the exception of AZA and 6-MP

Use of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) Use of natalizumab or vedolizumab

Use of TNF antagonists

Immunization with a live/attenuated vaccine

Use of anti-adhesion molecules (e.g., anti-MAdCAM-1)

  • In the opinion of the investigator, any new (since enrolling in Study GA29144), significant, uncontrolled comorbidity, such as neurological, cardiac (e.g., moderate to severe heart failure New York Heart Association [NYHA] Class III/IV), pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disorders (excluding CD)
  • Any patient who developed PML in Study GA29144
  • Any patient with neurological symptoms where suspected PML has not been ruled out

 

Part 2 (SM)

  • No exclusion criteria