ETRO: GA28951

Principal Investigator: John  Valentine
Keywords: Ulcerative Colitis , Etrolizumab Department: Gastroenterology
IRB Number: 00075954 Co Investigator:  
Specialty: Gastroenterology
Sub Specialties: Inflammatory Bowel Disease/Crohn's/Ulcerative Colitis
Recruitment Status: Recruiting

Contact Information

Heather Munk
heather.munk@hsc.utah.edu
801-587-9092

Brief Summary

Objectives

The objectives of this open-label extension−safety monitoring (OLE-SM) study are as follows:

Part 1 (Open-Label Extension; OLE)

To assess the long-term safety and efficacy of etrolizumab in patients eligible for Part 1 (OLE)

Part 2 (Safety Monitoring; SM)

Progressive multifocal leukoencephalopathy (PML) safety monitoring

Safety Objectives

The other safety objectives for this study are as follows:

Part 1 (OLE)

• To evaluate the incidence and severity of infection-related adverse events

• To evaluate the incidence 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

The exploratory objective for this study is as follows:
Part 1 (OLE)
• To evaluate histology at Week 108

Inclusion Criteria

In order to participate in this study (IRB#75954) participants must have first been enrolled in either IRB#81262 or IRB#75857. IRB#81262 have been approved for 5 participants. IRB#75857 have been approved for 5 participants. At this time enrollment in the study (IRB#75954) is expected to be 5 participants.

Inclusion Criteria Part 1 (OLE)

• Patients who were previously enrolled in the Phase II OLE study or the Phase III
controlled studies and meet the eligibility criteria for treatment with open-label
etrolizumab as described in Table 1 (see Section 3.1.1.1) may enroll in Part 1 (OLE)
of the study. These patients must provide written informed consent and comply with
the requirements of the OLE-SM protocol.
Patients not in safety follow-up or PML follow-up within Study GA27927 and
whose last dose of etrolizumab is in July 2016 may enroll in Part 1 (OLE) of
Study GA28951, if eligible, and receive their first dose in this study 4 weeks
after their last dose in Study GA27927. On occasions where this first dose of
etrolizumab cannot be administered in accordance with these requirements, the
first dose of etrolizumab is to be administered with a maximum delay of
2 weeks (i.e., up to 6 weeks after their last dose of etrolizumab in
Study GA27927).
Eligible patients who exit from Study GA28948 or GA28949 at Week 10
because they did not achieve either clinical remission or required the use of
rescue medication prior to the Week 10 timepoint should not receive their first
dose of open-label etrolizumab in Study GA28951 until 2 weeks after the
Week 10 timepoint in the Phase III controlled study to allow for adalimumab
washout. The first dose of etrolizumab given to these patients entering the
Study GA28951 should not exceed 4 weeks following the Week 10 timepoint
from the Phase III controlled study.
Patients who remain in Study GA28948 or GA28949 through Week 14 because
they have achieved clinical remission may enroll in the OLE (Part 1) of
Study GA28951 at Week 14. The first dose of open-label etrolizumab will be
given on Day 1 upon enrollment into Part 1 (OLE) of Study GA28951. The first
dose of etrolizumab given to the patients entering Study GA28951 should not
exceed 2 weeks following the Week 14 timepoint from the Phase III controlled
study.
• For women who are not postmenopausal (at least 12 months of
non−therapy-induced amenorrhea) or surgically sterile (i.e., absence of ovaries
and/or uterus): agreement to remain abstinent or 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) for the duration of the study (i.e., during
the treatment period) and for at least 24 weeks after the last dose of study drug
(see Appendix 4).
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and 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 (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, as
defined below:
With female partners of childbearing potential or pregnant female partners,
men must remain abstinent or use a condom during the treatment period and
for at least 24 weeks after the last dose of study drug to avoid exposing the
embryo to study drug. Men must refrain from donating sperm during this
same period.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and 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)

 

Part 2 (SM)
• Patients whose safety follow-up or PML follow-up is not completed within
Study GA27927 and patients who had their last dose of etrolizumab in July 2016
in Study GA27927 and are not eligible or choose not to enroll in Part 1 (OLE)
• Patients who participated in one of the etrolizumab Phase III studies ( GA28948,
GA28949, GA28950, GA29102, and GA29103) and are not eligible or chose not to
enroll in Part 1 (OLE)
• Patients who transfer from 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).


Table 1: Eligibility Criteria for Enrollment into Part 1 of Open-Label Extension - Safety Monitoring

Protocol Number(s)

 

Title

 

Eligibility and Timing for Enrollment

GA28950

Phase III, randomized, double-blind, placebo-controlled, multicenter study of the

efficacy and safety of etrolizumab during induction and maintenance in patients with moderate to severe active ulcerative colitis who are refractory to or intolerant of TNF inhibitors

 

Treatment Arms: etrolizumab, placebo

At end of Induction Phase:

  • Patients who performed the Week 14 visit who did not meet the criteria for

clinical response b

NOTE: Patients in the United States who require IS beyond 10 weeks (of the 14-week Induction Phase) are not permitted to enroll in Part 1 (OLE).

During the Maintenance Phase

  • Patients who met the criteria for clinical relapse c
  • Patients receiving rescue medications, as defined in the Study GA28950 protocol

All remaining patients at the end of Week 66 visit (completion of Maintenance Phase)

GA29102

Phase III, randomized, double-blind,

placebo-controlled, multicenter study to evaluate the efficacy (maintenance of remission) and safety of etrolizumab compared with placebo in patients with moderate to severe active ulcerative colitis who are naive to TNF inhibitors

 

Treatment Arms: etrolizumab, placebo

At the end of the Induction Phase:

  • Patients who performed the Week 10 visit and who have not achieved clinical response b at Week 10

NOTE:  Patients in the United States who require IS beyond the end of the Induction Phase are not permitted to enroll in PART 1 (OLE).

During the Maintenance Phase:

• Patients who met the criteria for clinical relapse

• Patients receiving rescue medications, as defined in the GA29102 protocol

All remaining patients at the end of Week 62 visit (completion of Maintenance Phase)

5-ASA = 5-aminosalicylates; IS = immunosuppressant; OLE = open-label extension; OLE-SM = open-label extension−safety monitoring; pMCS = partial Mayo Clinic Score; SM = safety monitoring; TNF = tumor necrosis factor; UC = ulcerative colitis.

a Patients are to receive their first dose of etrolizumab in this protocol 4 weeks after their last dose of study medication in Studies GA28950 and GA29102; as specified above for Studies GA28948 and GA28949 and as described in the washout schedule for Study GA29103. On occasions where this first dose of etrolizumab cannot be administered in accordance with these requirements, the first dose of etrolizumab is to be administered with a maximum delay of 2 weeks.

b Definition of Clinical Response: MCS with ≥ 3-point decrease and 30% reduction from baseline as well as ≥ 1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1.

c Definition of Clinical Relapse: Clinical relapse is defined as an increase in pMCS ≥ 3 points compared with induction timepoint (Week 10 or 14) AND absolute pMCS of ≥ 5 AND an endoscopy subscore of ≥ 2.

 

 

 

Exclusion Criteria

 

Exclusion Criteria

Part 1 (OLE)

• Withdrawal of consent from the Phase II OLE study or any of the Phase III studies
• Patients who discontinued etrolizumab/etrolizumab placebo prior to Week 10 or did
not perform the Week 10 visit of the Phase III Studies GA28948, GA28949,
GA29102, and GA29103
• Patients who discontinued etrolizumab/etrolizumab placebo prior to Week 14 or did
not perform the Week 14 visit of the Phase III Study GA28950
Etrolizumab—F. Hoffmann-La Roche Ltd
64/Protocol GA28951, Version 6
• Inability to comply with the study protocol, in the opinion of the investigator
• Patients not compliant in the Phase II OLE or Phase III studies or did not complete
the required washout period for an active comparator in Studies GA28948,
GA28949, and GA29103
• Pregnancy or lactation
Exclusion Due to Safety Reasons
• Patients who developed an anaphylactic/anaphylactoid or severe allergic reaction to
study medication during the Phase II OLE or Phase III studies
• Patients who experienced or have an ongoing serious infection event (except for
those listed below) should not receive study drug until the event has completely
resolved and treatment with anti-infective medications has been completed
• Patients who experienced a specific de novo or reactivated serious viral infection
such as hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV during the
Phase II OLE or Phase III studies
• Patients who develop cytomegalovirus (CMV) colitis leading to early treatment
discontinuation in the Phase II OLE or Phase III studies
• Patients who develop life-threatening infections during the Phase II OLE or
Phase III studies
• 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 the Phase II OLE or Phase III studies
• Receipt of the following since commencement of the Phase II OLE or Phase III
controlled studies:
Any investigational treatment, including investigational vaccines
Use of agents that deplete B or T cells (e.g., alemtuzumab or visilizumab),
except AZA and 6-MP
Use of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF)
Patients who have previously received rituximab, natalizumab, vedolizumab, or
efalizumab may not enter the study
Immunization with a live/attenuated vaccine
• In the opinion of the investigator, any new (since enrolling in the Phase II OLE or
Phase III controlled studies), 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 UC)
• Any patient who developed PML in the Phase II OLE or Phase III studies
• Any patient with neurological symptoms where suspected PML has not been ruled out
 
Part 2 (SM)

No exclusion criteria