Crohn's Disease
Conditions
Keywords
Crohn's Disease, GED 0301, Mongersen, Safety, Irritable Bowel Disease
Brief summary
The purpose of this study is to assess long-term safety data of GED-0301 for a period of up to 208 weeks in adult subjects (i.e., ≥ 18 years of age) who participated in the core Phase 3 GED-0301-CD-002 and GED-0301-CD-003 studies and adolescent subjects (i.e., 12 to 17 years of age) who participated in the core Phase 3 GED-0301-CD-003 study. Although all subjects will receive active treatment, this study is double-blinded for the entire 208 weeks for the purpose of preserving the blind of the subject's treatment allocation in the initial, core Phase 3 GED-0301 study. The GED-0301-CD-003 trial was not initiated; see detailed description.
Detailed description
This is a long-term active treatment study in patients with Crohn's disease (CD). Subjects who met the early escape criteria in Study GED-0301-CD-002, or subjects who completed Study GED-0301-002 or GED-0301-003, may be eligible for this study. Primary objective is to assess long-term safety of GED 0301. Additional efficacy and patient reported outcomes will be explored. There are 5 possible treatment groups for GED-0301-CD-002 Subjects (Groups 1-5). There are 3 possible treatment groups for GED-0301-CD-003 subjects (Groups 1-3). Treatment is assigned based on clinical improvement achieved or not achieved from the core GED-0301 study. 1. continuous GED-0301 160 mg once daily for 12 weeks, followed by alternating placebo once daily for 4 weeks with GED-0301 160 mg once daily for 4 weeks, through Week 208; 2. alternating GED-0301 160 mg once daily for 4 weeks with placebo once daily for 4 weeks, through Week 208; 3. alternating placebo once daily for 4 weeks with GED-0301 160 mg once daily for 4 weeks, through Week 208; 4. continuous GED-0301 40 mg once daily through Week 208; 5. alternating placebo once daily for 4 weeks, followed by GED-0301 40 mg once daily for 4 weeks, through Week 208. The GED-0301-CD-003 trial was not initiated; the GED-0301 program was terminated; no safety findings were noted.
Interventions
DRUGGED-0301
Mongersen
OTHERPlacebo
Placebo
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Adult Subjects: Subjects must satisfy the following criteria to be screened and enrolled in the study: * Male or female ≥ 18 years of age. * Subject must have participated in the GED-0301-CD-002 or GED 0301 CD 003 study. * Subject must use protocol approved contraception. Inclusion Criteria for Adolescent Subjects: Adolescent subjects must satisfy the following criteria to be screened and enrolled in the study * Male or female 12 to 17 years of age. * Subject must have participated in the GED 0301 CD 003 study. * Subject is able to swallow the IP tablets. * Subject must use protocol approved contraception.
Exclusion criteria
for Adult and Adolescent Subjects: The presence of any of the following will exclude a subject from screening and enrollment: * Subject had experienced a serious adverse event (SAE) related to the investigational product while participating in the previous Phase 3 GED-0301 study. * Subject has initiated biologic agents, such as TNF-α blockers or integrin antagonists. * Subject is pregnant or breastfeeding. * Subject has developed a known hypersensitivity to oligonucleotides, GED 0301 or any ingredient in the investigational product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | From the first day of GED-0301 until 28 days after the last dose of IP; maximum treatment duration was 16.1 weeks in the GED-0301 40 mg Alt dose; 16.3 weeks in the GED 40 mg continuous dose and 56.1 weeks in the GED-0301 160 mg Alt dose | A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of GED-0301 and up to 28 days after the last GED- 0301 dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale; Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain. |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Netherlands, Norway, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
310 adult participants who had previously participated in the main study GED-0301-CD-002 were enrolled at 167 study sites in 29 countries.
Pre-assignment details
Includes participants with Crohn's disease who had previously participated in the main study GED-0301-CD-002 through Week 12 at minimum and completed participation through the last treatment visit at Week 52, or met the early escape criteria and were discontinued beginning at Week 12 through Week 52.
Participants by arm
| Arm | Count |
|---|---|
| GED-0301 40 mg 4 Weeks Alt Participants received alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 208 | 4 |
| GED-0301 40 mg Participants received continuous GED-0301 40 mg daily, up to week 208. | 13 |
| GED-0301 160 mg 4 Weeks Alt Participants received one of three dose regimens up to week 208:
1\) alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks or (2) alternating GED-0301 160 mg daily for 4 weeks and placebo daily for 4 weeks or (3) GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks | 293 |
| Total | 310 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 25 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 101 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 |
| Overall Study | Miscellaneous | 0 | 0 | 3 |
| Overall Study | Study Terminated by Sponsor | 4 | 12 | 144 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 17 |
Baseline characteristics
| Characteristic | GED-0301 40 mg | GED-0301 160 mg 4 Weeks Alt | GED-0301 40 mg 4 Weeks Alt | Total |
|---|---|---|---|---|
| Age, Continuous | 41.8 Years STANDARD_DEVIATION 14.21 | 38.1 Years STANDARD_DEVIATION 12.3 | 35.3 Years STANDARD_DEVIATION 12.34 | 38.2 Years STANDARD_DEVIATION 12.37 |
| Baseline Crohn's Disease Activity (CDAI) Score | 309.2 units on a scale STANDARD_DEVIATION 43.1 | 307.5 units on a scale STANDARD_DEVIATION 62.74 | 316.9 units on a scale STANDARD_DEVIATION 96.9 | 307.7 units on a scale STANDARD_DEVIATION 62.33 |
| Duration of Crohn's Disease | 9.25 Years STANDARD_DEVIATION 6.307 | 10.56 Years STANDARD_DEVIATION 8.503 | 7.25 Years STANDARD_DEVIATION 6.529 | 10.46 Years STANDARD_DEVIATION 8.396 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 10 Participants | 0 Participants | 13 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Collected or Reported | 1 Participants | 10 Participants | 0 Participants | 11 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 264 Participants | 4 Participants | 277 Participants |
| Sex: Female, Male Female | 6 Participants | 136 Participants | 3 Participants | 145 Participants |
| Sex: Female, Male Male | 7 Participants | 157 Participants | 1 Participants | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 13 | 1 / 293 |
| other Total, other adverse events | 1 / 4 | 6 / 13 | 92 / 293 |
| serious Total, serious adverse events | 1 / 4 | 0 / 13 | 41 / 293 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208
A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of GED-0301 and up to 28 days after the last GED- 0301 dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale; Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.
Time frame: From the first day of GED-0301 until 28 days after the last dose of IP; maximum treatment duration was 16.1 weeks in the GED-0301 40 mg Alt dose; 16.3 weeks in the GED 40 mg continuous dose and 56.1 weeks in the GED-0301 160 mg Alt dose
Population: Safety population includes participants who were received at least one dose of GED-0301. Participants were included in the group corresponding to the treatment regimen they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GED 40 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE | 1 Participants |
| GED 40 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Drug-Related TEAE | 0 Participants |
| GED 40 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Severe TEAE | 0 Participants |
| GED 40 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Serious TEAE (SAE) | 1 Participants |
| GED 40 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Serious Drug-Related TEAE | 0 Participants |
| GED 40 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to IP Interruption | 0 Participants |
| GED 40 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to IP Withdrawal | 0 Participants |
| GED 40 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to Death | 0 Participants |
| GED-0301 40 mg | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Severe TEAE | 0 Participants |
| GED-0301 40 mg | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to IP Withdrawal | 1 Participants |
| GED-0301 40 mg | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Serious TEAE (SAE) | 0 Participants |
| GED-0301 40 mg | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Serious Drug-Related TEAE | 0 Participants |
| GED-0301 40 mg | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to IP Interruption | 0 Participants |
| GED-0301 40 mg | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE | 6 Participants |
| GED-0301 40 mg | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Drug-Related TEAE | 1 Participants |
| GED-0301 40 mg | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to Death | 0 Participants |
| GED-0301 160 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Severe TEAE | 38 Participants |
| GED-0301 160 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Drug-Related TEAE | 43 Participants |
| GED-0301 160 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE | 189 Participants |
| GED-0301 160 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Serious TEAE (SAE) | 41 Participants |
| GED-0301 160 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to IP Withdrawal | 27 Participants |
| GED-0301 160 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to IP Interruption | 7 Participants |
| GED-0301 160 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any Serious Drug-Related TEAE | 4 Participants |
| GED-0301 160 mg 4 Weeks Alt | Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | Any TEAE Leading to Death | 1 Participants |