Active Ulcerative Colitis
Conditions
Brief summary
The primary objective of the study is to evaluate the clinical activity of interferon beta-1a in participants with moderate to severe ulcerative colitis (UC). Secondary objectives of this study are to determine (i) the safety and tolerability of interferon beta-1a in participants with moderate to severe UC, and (ii) the percentage of participants, with a decrease in the Simple Clinical Colitis Activity Index (SCCAI) score of ≥3 points at Week 8.
Interventions
Avonex IM injection, self-administered per protocol
DRUGPlacebo
Placebo IM injection, self-administered per protocol.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Established diagnosis of ulcerative colitis (UC) for ≥6 months * 20 cm active disease at Screening endoscopy * Must have active UC with a Mayo Score/Disease Activity Index (DAI) of 6 to 13 points and moderate to severe disease on endoscopy (Mayo endoscopic score of at least 2) despite prior or concomitant treatment * Colonoscopy within past 5 years for extent of disease and to exclude polyps * For subjects with UC for more than 10 years, colonoscopy with appropriate biopsies within 1 year prior to Screening to exclude dysplasia and neoplasia. * Must be willing and able to practice effective birth control during the study and for 1 month after the last dose of study treatment. Key
Exclusion criteria
* Diagnosis of indeterminate colitis or Crohn's disease * Need for imminent surgery * Diagnosis of primary sclerosing cholangitis or toxic megacolon * Hemoglobin ≤9 g/dL * White blood cell count \< 3500 cells/mm\^3 * Lymphocyte count \<1000 cells/µL * Platelet count \<100,000 cells/µL * Female subjects who are pregnant or who wish to become pregnant during the study, or who are lactating * Known symptomatic colonic stricture * Stool cultures positive for enteric infection * History of malignant disease * History of major abdominal surgery (e.g., gastrectomy) within past 5 years * History of small bowel or colonic obstruction or resection * History of drug or alcohol abuse (as defined by the Investigator) within 2 years prior to Screening * Use of anti-diarrheal agents during the screening period * Previous participation in this study * Previous treatment with interferon beta or other interferon products NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Clinical Response | Baseline and Week 8 | Clinical response is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, accompanied by a decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore of 1 or less. Baseline was defined as the score collected during the screening period. The Mayo Score/Disease Activity Index (DAI) measures disease activity through assessment of 4 items: stool frequency, rectal bleeding, endoscopy findings, and Physician Global Assessment (PGA). Each item of the score is assessed on a 4-point scale, 0, 1, 2, or 3, with a higher score representing greater severity. In this study, the endoscopy subscore was expanded to a 5-point scale to increase sensitivity in this important dimension of the disease (0=normal/inactive disease, 4=deep ulceration). The Total Mayo Score can therefore range from 0 to13 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Up to 16 weeks | An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE, can therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AE's were analyzed based on the principle of treatment emergence. An AE was regarded as treatment-emergent if it was not present prior to receiving the first injection but subsequently appeared, or if it was present prior to receiving the first injection and subsequently worsened in severity. |
| Percentage of Participants With a Decrease on Simple Clinical Colitis Activity Index (SCCAI) of ≥3 Points at Week 8 | Baseline and Week 8 | The SCCAI measures disease activity as defined by both participants and examiners and includes the following 13 items: general well-being, abdominal pain, bowel frequency, stool consistency, bleeding, anorexia, nausea or vomiting, abdominal tenderness, extra-intestinal complications (eye, mouth, joint, skin), temperature, sigmoidoscopic assessment, nocturnal bowel movements, and urgency of defecation. Scores range from 0 to 19 points, and scores \<2.5 have been shown to correlate with Patient-Defined Remission, and a decrease of \>1.5 points from Baseline correlates with Patient-Defined Significant Improvement. Baseline is defined as the mean of the screening and visit 1 scores. |
Countries
Canada, Czechia, Hungary, Poland, Russia, Slovakia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Interferon Beta-1a Interferon beta-1a 30 µg intramuscular (IM) injection twice weekly for 12 weeks | 62 |
| Placebo Placebo IM injection twice weekly for 12 weeks | 61 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 |
| Overall Study | Physician Decision | 0 | 4 |
| Overall Study | Protocol deviation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Interferon Beta-1a | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 41.1 years | 41.0 years | 41.0 years |
| Sex: Female, Male Female | 19 Participants | 26 Participants | 45 Participants |
| Sex: Female, Male Male | 43 Participants | 35 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 62 | 20 / 61 |
| serious Total, serious adverse events | 1 / 62 | 3 / 61 |
Outcome results
Primary
Percentage of Participants With a Clinical Response
Clinical response is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, accompanied by a decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore of 1 or less. Baseline was defined as the score collected during the screening period. The Mayo Score/Disease Activity Index (DAI) measures disease activity through assessment of 4 items: stool frequency, rectal bleeding, endoscopy findings, and Physician Global Assessment (PGA). Each item of the score is assessed on a 4-point scale, 0, 1, 2, or 3, with a higher score representing greater severity. In this study, the endoscopy subscore was expanded to a 5-point scale to increase sensitivity in this important dimension of the disease (0=normal/inactive disease, 4=deep ulceration). The Total Mayo Score can therefore range from 0 to13 points.
Time frame: Baseline and Week 8
Population: Intent-to-treat (ITT): Defined as all randomized participants who received at least one dose of study treatment for whom a baseline measure was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interferon Beta-1a | Percentage of Participants With a Clinical Response | 53 percentage of participants |
| Placebo | Percentage of Participants With a Clinical Response | 44 percentage of participants |
Secondary
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE, can therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AE's were analyzed based on the principle of treatment emergence. An AE was regarded as treatment-emergent if it was not present prior to receiving the first injection but subsequently appeared, or if it was present prior to receiving the first injection and subsequently worsened in severity.
Time frame: Up to 16 weeks
Population: Safety Population; participants who were randomized and received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interferon Beta-1a | Number of Participants With Adverse Events (AEs) | 52 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | 35 participants |
Secondary
Percentage of Participants With a Decrease on Simple Clinical Colitis Activity Index (SCCAI) of ≥3 Points at Week 8
The SCCAI measures disease activity as defined by both participants and examiners and includes the following 13 items: general well-being, abdominal pain, bowel frequency, stool consistency, bleeding, anorexia, nausea or vomiting, abdominal tenderness, extra-intestinal complications (eye, mouth, joint, skin), temperature, sigmoidoscopic assessment, nocturnal bowel movements, and urgency of defecation. Scores range from 0 to 19 points, and scores \<2.5 have been shown to correlate with Patient-Defined Remission, and a decrease of \>1.5 points from Baseline correlates with Patient-Defined Significant Improvement. Baseline is defined as the mean of the screening and visit 1 scores.
Time frame: Baseline and Week 8
Population: Intent-to-treat (ITT): Defined as all randomized participants who received at least one dose of study treatment for whom a baseline SCCAI ≥ 3 was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interferon Beta-1a | Percentage of Participants With a Decrease on Simple Clinical Colitis Activity Index (SCCAI) of ≥3 Points at Week 8 | 64 percentage of participants |
| Placebo | Percentage of Participants With a Decrease on Simple Clinical Colitis Activity Index (SCCAI) of ≥3 Points at Week 8 | 46 percentage of participants |