Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis
Brief summary
To evaluate the efficacy and safety of Neihulizumab (ALTB-168) administered intravenously in patients with moderate to severe active ulcerative colitis who are refractory or intolerant to anti-Tumor Necrosis Factor α and/or anti-integrin treatments.
Detailed description
This is a Phase II, open label, single arm, multiple dose proof of principle study to test the efficacy and safety of Neihulizumab in patients with moderate to severe active ulcerative colitis and who has failed or are intolerant to anti-TNFα and/or anti-integrin therapy. A minimum of 30 patients and a maximum of 40 will be recruited in 1 dosing group. For efficacy evaluation, the primary endpoint is the proportion of patients with clinical response, defined as ≥ 3- point reduction in MCS, a 30% or greater decrease from the baseline score, and with a 1-point or greater decrease of the rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1 at Week 12. Safety assessments will consist of evaluating physical examination, vital signs (blood pressure, heart rate, respiratory rate, body temperature and oxygen saturation), safety laboratory tests, adverse events and tolerability.
Interventions
BIOLOGICALALTB-168
monoclonal antibody
Sponsors
AltruBio Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients must provide written informed consent; 2. Age 18-75 years; 3. Diagnosis of UC ≥ 12 weeks prior to screening by full colonoscopy (i.e., ≥ 12 weeks after first diagnosis by a physician according to American College of Gastroenterology guidelines); 4. Moderate-to-severe active UC, at time of screening, defined as: 1. Mayo Clinic Score (MCS) of 6 points or higher, AND 2. a centrally read MCS endoscopic subscore of grade 2 or higher, AND 3. MCS rectal bleeding subscore of 1 point or higher, AND 4. disease extending 15 cm or more from the anal verge; 5. Stable doses of concomitant medications, including : 1. Stable oral corticosteroids (i.e., ≤ 20 mg/day of prednisone, ≤ 9 mg/day of budesonide) ≥ 2 weeks before D1 dosing; Taper of oral corticosteroids per Investigator's discretion during the study is allowed; 2. Stable oral 5-amyinosalicylic acid dose ≥ 2 weeks before D1 dosing; 3. Stable immunosuppressant including azathioprine, mercaptopurine, or methotrexate ≥ 8 weeks before D1 dosing. Patients taking methotrexate also are advised to take folic acid 1 mg/day or equivalent if there is no contraindication; 4. Stable doses of probiotics ≥ 2 weeks before D1 dosing; 5. Stable anti-diarrheas ≥ 2 weeks before D1 dosing; 6. Patients must have previously received anti-tumor necrosis factor alpha (anti- TNF alpha and/or anti-integrin therapy for UC and demonstrated an inadequate response, loss of response, or intolerance, and must have discontinued therapy ≥ 8 weeks before D1 dosing; 7. Patients previously treated with cyclosporine or tacrolimus must have discontinued therapy ≥ 4 weeks before D1 dosing; 8. Topical corticosteroids and topical 5-amyinosalicylic acid preparations must have been withdrawn ≥ 2 weeks before D1 dosing; 9. Nonsteroidal anti-inflammatory drugs (NSAIDs) must have been discontinued ≥ 4 weeks before D1 dosing; 10. Tofacitinib or other Janus kinase (JAK) inhibitors must have been discontinued ≥ 2 weeks before D1 dosing; 11. Patients previously treated with tube feeding, defined formula diets, or parenteral alimentation/nutrition must have discontinued treatment 3 weeks before D1 dosing; 12. Females with reproductive potential must have a negative pregnancy test result before enrollment. Men and women with reproductive potential have to be willing to use a highly effective method of contraception from study start to ≥ 3 months after the final dose of the study drug. A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year).
Exclusion criteria
GI related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Patients With Clinical Response at Week 12 | week 12 | The clinical response is defined as a ≥ 3-point reduction in Mayo Clinic Score, a 30% or greater decrease from the baseline score, and with a 1-point or greater decrease of the rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1, The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Patients With Clinical Response (mITT) | weeks 6,16, 20 and 26 | The proportion of patients with clinical response defined as a ≥2-point decrease in partial MCS (pMCS), and with a 1 point or greater decrease of the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1. The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement. |
| The Proportion of Patients With Clinical Remission | weeks 6,16, 20 and 26 | The number of patients with clinical remission, defined as MCS of 2 or lower (or pMCS of 1 or lower) and no subscore higher than 1. The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement. |
| Flexible Sigmoidoscopy Subscore Changes From Baseline | Baseline, week 12- and week 26 after the first treatment | The mean (SD) observed flexible sigmoidoscopy subscore change from baseline (CFB). Baseline is defined as the last available assessment prior to the first administration of the study drug. The sigmoidoscopic improvement is defined as any decrease in Mayo Clinic Score (MCS) endoscopic subscore, at Weeks 12 and 26. MCS range is 1-3. The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement. |
| The Number of Patients With Mucosal Healing | at 12- and 26-week after the first treatment | The mucosal healing is defined as an absolute subscore for endoscopy of 0 or 1 The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement. |
| Change of Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline | at 12- and 26-week after the first treatment | Number of Participants with a Clinically Significant Difference in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline, to Week 12 and Week 26. The IBDQ is a questionnaire used for an assessment of Health Related Quality of Life (HRQoL) in patients with the Inflammatory Bowel Disease (IBD). The IBDQ has a possible score range of 32 (minimum) to 224 (maximum), where a higher score indicates better HRQoL. A difference of 16 points from Baseline Assessment (Baseline Score) to Week 12, and Baseline Assessment (Baseline Score) to Week 26, is considered clinically significant. The outcome measure is assessed by comparing each patient's change in individual IBDQ score from Baseline to Week 12, and from Baseline to Week 26. Patients who achieved the 16 point difference (improvement of the IBDQ score from the baseline indicating the Clinically Significant Difference) are included as responders to the treatment. |
| The Number of Patients With Inflammatory IBDQ Response | at 12- and 26-week after the first treatment | The Inflammatory Bowel Disease Questionnaire (IBDQ) has a possible score range of 32 (minimum) to 224 (maximum), where a higher score indicates better Health Related Quality of Life (HRQoL). A difference of 16 points from Baseline to Week 12 and Baseline to Week 26, is considered clinically significant. The outcome measure will be assessed by comparing each patient's change in individual IBDQ score from Baseline to Week 12, and from Baseline to Week 26, to assess whether a response was seen. |
| Change of Histological Activity Grade From Baseline Using the Geboes System | at 12- and 26-week after the first treatment | The number of patients with histological activity Geboes Score ≤ 3.1 (worst of both rectum and sigmoid colon). The original Geboes grade system is from Grade 0 to Grade 5. The following are the grades: Grade 0: Architectural changes Grade 1: Chronic inflammatory infiltrate Grade 2A: Eosinophils in lamina propria Grade 2B: Neutrophils in lamina propria Grade 3: Neutrophils in epithelium Grade 4:Crypt destruction Grade 5: Erosions and ulcerations |
| The Number of Patients With Histological Healing | at 12- and 26-week after the first treatment | The histological healing is defined as histological grade = 0 |
Other
| Measure | Time frame | Description |
|---|---|---|
| CRP Changes From Baseline (CFB) (Exploratory) | Am 4, Weeks 4, 9, 12, 16, 20, 26; Am 1-3 weeks 4,8,12,16,20, 26 | Change in biomarkers of CRP (C-reactive protein). C-reactive protein (CRP) is a biomarker produced by your liver in response to inflammation. Normal CRP value is below 1 mg/L. 1-3 mg/L is in the yellow zone, indicating some inflammation \>3 mg/L is in the red zone, meaning there is significant inflammation |
| Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Am 4, Weeks 4, 9, 12, 16, 20, 26; Am 1-3 weeks 4,8,12,16,20, 26 | Faecal calprotectin changes from the baseline at Week 4, 9, 12, 16, 20, and 26 were measured. Baseline is defined as the last available assessment prior to the first administration of the study drug. Faecal calprotectin is measured as mcg/g, so the results come back as a numeric value. A level under 50 is considered to be 'normal'. A level between 50 and 100, coupled with digestive symptoms, means IBS is likely. Lower level means improvement. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at 12 centers locate in North America and Puerto Rico from May 2018 to June 2020. It was a 24 weeks open label, single arm, multiple dose proof of principle study.
Participants by arm
| Arm | Count |
|---|---|
| ALTB-168 Intravenous doses of ALTB-168
ALTB-168: monoclonal antibody | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | disease relapse | 1 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | ALTB-168 |
|---|---|
| Age, Categorical Enrolled Under Amendment 1-3 <=18 years | 0 Participants |
| Age, Categorical Enrolled Under Amendment 1-3 >=65 years | 1 Participants |
| Age, Categorical Enrolled Under Amendment 1-3 Between 18 and 65 years | 9 Participants |
| Age, Categorical Enrolled Under Amendment 4 <=18 years | 0 Participants |
| Age, Categorical Enrolled Under Amendment 4 >=65 years | 0 Participants |
| Age, Categorical Enrolled Under Amendment 4 Between 18 and 65 years | 14 Participants |
| Age, Continuous Amendment 1-3 | 37 years |
| Age, Continuous Amendment 4 | 35.5 years |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 7 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 15 Participants |
| Race/Ethnicity, Customized Ethnicity Not reported | 2 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Enrolled under Amendment 1~3 Female | 6 Participants |
| Sex: Female, Male Enrolled under Amendment 1~3 Male | 4 Participants |
| Sex: Female, Male Enrolled under Amendment 4 Female | 7 Participants |
| Sex: Female, Male Enrolled under Amendment 4 Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 14 |
| other Total, other adverse events | 9 / 10 | 13 / 14 |
| serious Total, serious adverse events | 1 / 10 | 0 / 14 |
Outcome results
Primary
The Proportion of Patients With Clinical Response at Week 12
The clinical response is defined as a ≥ 3-point reduction in Mayo Clinic Score, a 30% or greater decrease from the baseline score, and with a 1-point or greater decrease of the rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1, The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement.
Time frame: week 12
Population: The full analysis set includes all participants who received at least 1 dose of study drug. The response rates were calculated using non-responder imputation, where participants with a missing scores at week 12 were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Response at Week 12 | 22.2 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Response at Week 12 | 50 percentage of total number of patients |
Secondary
Change of Histological Activity Grade From Baseline Using the Geboes System
The number of patients with histological activity Geboes Score ≤ 3.1 (worst of both rectum and sigmoid colon). The original Geboes grade system is from Grade 0 to Grade 5. The following are the grades: Grade 0: Architectural changes Grade 1: Chronic inflammatory infiltrate Grade 2A: Eosinophils in lamina propria Grade 2B: Neutrophils in lamina propria Grade 3: Neutrophils in epithelium Grade 4:Crypt destruction Grade 5: Erosions and ulcerations
Time frame: at 12- and 26-week after the first treatment
Population: Study participants who received at least one dose of ALTB-168
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Change of Histological Activity Grade From Baseline Using the Geboes System | Week 12 | 0 participants |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Change of Histological Activity Grade From Baseline Using the Geboes System | Week 26 | 1 participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Change of Histological Activity Grade From Baseline Using the Geboes System | Week 12 | 2 participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Change of Histological Activity Grade From Baseline Using the Geboes System | Week 26 | 4 participants |
Secondary
Change of Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline
Number of Participants with a Clinically Significant Difference in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline, to Week 12 and Week 26. The IBDQ is a questionnaire used for an assessment of Health Related Quality of Life (HRQoL) in patients with the Inflammatory Bowel Disease (IBD). The IBDQ has a possible score range of 32 (minimum) to 224 (maximum), where a higher score indicates better HRQoL. A difference of 16 points from Baseline Assessment (Baseline Score) to Week 12, and Baseline Assessment (Baseline Score) to Week 26, is considered clinically significant. The outcome measure is assessed by comparing each patient's change in individual IBDQ score from Baseline to Week 12, and from Baseline to Week 26. Patients who achieved the 16 point difference (improvement of the IBDQ score from the baseline indicating the Clinically Significant Difference) are included as responders to the treatment.
Time frame: at 12- and 26-week after the first treatment
Population: Study participants who received at least one dose of ALTB-168. Missing data imputed as non-responders (i.e. Amd 1-3: Week 12 - 3 missing; Week 26 - 8 missing; and Amd 4: Week 12 - 0 missing; Week 26 - 6 missing).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Change of Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline | Week 12 | 2 participants |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Change of Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline | Week 26 | 1 participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Change of Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline | Week 12 | 9 participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Change of Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline | Week 26 | 7 participants |
Secondary
Flexible Sigmoidoscopy Subscore Changes From Baseline
The mean (SD) observed flexible sigmoidoscopy subscore change from baseline (CFB). Baseline is defined as the last available assessment prior to the first administration of the study drug. The sigmoidoscopic improvement is defined as any decrease in Mayo Clinic Score (MCS) endoscopic subscore, at Weeks 12 and 26. MCS range is 1-3. The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement.
Time frame: Baseline, week 12- and week 26 after the first treatment
Population: Study participants who entered the study under amendment 1-3 (n=9) and participans who entered the study under amendment 4 (n=14) have been inlcuded in this analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Flexible Sigmoidoscopy Subscore Changes From Baseline | Flexible Sigmoidoscopy Score at Baseline | 2.7 score on a scale | Standard Deviation 0.5 |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Flexible Sigmoidoscopy Subscore Changes From Baseline | Flexible Sigmoidoscopy Score at week 12 CFB | -0.7 score on a scale | Standard Deviation 1.03 |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Flexible Sigmoidoscopy Subscore Changes From Baseline | Flexible Sigmoidoscopy Score at week 26 CFB | 0 score on a scale | Standard Deviation 0 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Flexible Sigmoidoscopy Subscore Changes From Baseline | Flexible Sigmoidoscopy Score at Baseline | 2.6 score on a scale | Standard Deviation 0.5 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Flexible Sigmoidoscopy Subscore Changes From Baseline | Flexible Sigmoidoscopy Score at week 12 CFB | -0.6 score on a scale | Standard Deviation 1 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Flexible Sigmoidoscopy Subscore Changes From Baseline | Flexible Sigmoidoscopy Score at week 26 CFB | -0.6 score on a scale | Standard Deviation 1.27 |
Secondary
The Number of Patients With Histological Healing
The histological healing is defined as histological grade = 0
Time frame: at 12- and 26-week after the first treatment
Population: Study participants who received at least one dose of ALTB-168. Missing data imputed as non-responders (i.e. Amd 1-3: Week 12 - 4 missing; Week 26 - 8 missing; and Amd 4: Week 12 - 2 missing; Week 26 - 7 missing).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Number of Patients With Histological Healing | Week 12 | 0 Participants |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Number of Patients With Histological Healing | Week 26 | 0 Participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Number of Patients With Histological Healing | Week 12 | 0 Participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Number of Patients With Histological Healing | Week 26 | 0 Participants |
Secondary
The Number of Patients With Inflammatory IBDQ Response
The Inflammatory Bowel Disease Questionnaire (IBDQ) has a possible score range of 32 (minimum) to 224 (maximum), where a higher score indicates better Health Related Quality of Life (HRQoL). A difference of 16 points from Baseline to Week 12 and Baseline to Week 26, is considered clinically significant. The outcome measure will be assessed by comparing each patient's change in individual IBDQ score from Baseline to Week 12, and from Baseline to Week 26, to assess whether a response was seen.
Time frame: at 12- and 26-week after the first treatment
Population: Study participants who received at least one dose of ALTB-168. Missing data imputed as non-responders (i.e. Amd 1-3: Week 12 - 3 missing; Week 26 - 8 missing; and Amd 4: Week 12 - 0 missing; Week 26 - 6 missing).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Number of Patients With Inflammatory IBDQ Response | Week 12 | 2 participants |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Number of Patients With Inflammatory IBDQ Response | Week 26 | 1 participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Number of Patients With Inflammatory IBDQ Response | Week 12 | 9 participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Number of Patients With Inflammatory IBDQ Response | Week 26 | 7 participants |
Secondary
The Number of Patients With Mucosal Healing
The mucosal healing is defined as an absolute subscore for endoscopy of 0 or 1 The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement.
Time frame: at 12- and 26-week after the first treatment
Population: Study participants who received at least one dose of ALTB-168. Missing data imputed as non-responders (i.e. Amd 1-3: Week 12 - 3 missing; Week 26 - 8 missing; and Amd 4: Week 12 - 2 missing; Week 26 - 7 missing).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Number of Patients With Mucosal Healing | Week 12 | 2 participants |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Number of Patients With Mucosal Healing | Week 26 | 0 participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Number of Patients With Mucosal Healing | Week 12 | 4 participants |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Number of Patients With Mucosal Healing | Week 26 | 3 participants |
Secondary
The Proportion of Patients With Clinical Remission
The number of patients with clinical remission, defined as MCS of 2 or lower (or pMCS of 1 or lower) and no subscore higher than 1. The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement.
Time frame: weeks 6,16, 20 and 26
Population: The full analysis set includes all participants who received at least 1 dose of study drug. Response rates were calculated using non-responder imputation, where participants with a missing information were counted as non-responders. 23 participants are included in the study analysis. 9 participants from the pilot study (protocol Amendments 1-3) and 14 participants from the main study (protocol Amendment 4).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Remission | Clinical response at week 6 | 11.1 percentage of total number of patients |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Remission | Clinical response at week 20 | 0 percentage of total number of patients |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Remission | Clinical response at week 26 | 11.1 percentage of total number of patients |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Remission | Clinical response at week 16 | 0 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Remission | Clinical response at week 26 | 21.4 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Remission | Clinical response at week 6 | 35.7 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Remission | Clinical response at week 16 | 35.7 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Remission | Clinical response at week 20 | 35.7 percentage of total number of patients |
Secondary
The Proportion of Patients With Clinical Response (mITT)
The proportion of patients with clinical response defined as a ≥2-point decrease in partial MCS (pMCS), and with a 1 point or greater decrease of the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1. The colonic site with maximum inflammation was determined by Mayo endoscopic subscore (MES) defined as follows: normal (0 points); erythema, decreased vascular pattern, mild friability (1 point); absent vascular pattern, friability, erosions (2 points); and spontaneous bleeding or ulceration (3 points). Lower score means disease improvement.
Time frame: weeks 6,16, 20 and 26
Population: The full analysis set includes all participants who received at least 1 dose of study drug. Response rates were calculated using non-responder imputation, where participants with a missing information were counted as non-responders. 23 participants are included in the study analysis. 9 participants from the pilot study (protocol Amendments 1-3) and 14 participants from the main study (protocol Amendment 4).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Response (mITT) | Clinical Response at week 6 | 33.3 percentage of total number of patients |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Response (mITT) | Clinical Response at week 16 | 0 percentage of total number of patients |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Response (mITT) | Clinical Response at week 20 | 11.1 percentage of total number of patients |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | The Proportion of Patients With Clinical Response (mITT) | Clinical Response at week 26 | 11.1 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Response (mITT) | Clinical Response at week 26 | 35.7 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Response (mITT) | Clinical Response at week 6 | 57.1 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Response (mITT) | Clinical Response at week 20 | 64.3 percentage of total number of patients |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | The Proportion of Patients With Clinical Response (mITT) | Clinical Response at week 16 | 64.3 percentage of total number of patients |
Other Pre-specified
Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker
Faecal calprotectin changes from the baseline at Week 4, 9, 12, 16, 20, and 26 were measured. Baseline is defined as the last available assessment prior to the first administration of the study drug. Faecal calprotectin is measured as mcg/g, so the results come back as a numeric value. A level under 50 is considered to be 'normal'. A level between 50 and 100, coupled with digestive symptoms, means IBS is likely. Lower level means improvement.
Time frame: Am 4, Weeks 4, 9, 12, 16, 20, 26; Am 1-3 weeks 4,8,12,16,20, 26
Population: Study participants who received at least one dose of ALTB-168
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 9 (Am 4, week 8 Am 1-3) | 223.17 mcg/g | Standard Deviation 605.971 |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 16 | NA mcg/g | — |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 4 (CFB) | 113.89 mcg/g | Standard Deviation 753.179 |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 20 | NA mcg/g | — |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 12 | 923.00 mcg/g | Standard Deviation 997.162 |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 26 | NA mcg/g | — |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Baseline | 682.80 mcg/g | Standard Deviation 548.153 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 26 | -780.30 mcg/g | Standard Deviation 633.292 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Baseline | 1283.49 mcg/g | Standard Deviation 758.019 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 4 (CFB) | -203.30 mcg/g | Standard Deviation 704.559 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 9 (Am 4, week 8 Am 1-3) | -384.47 mcg/g | Standard Deviation 662.42 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 12 | -584.17 mcg/g | Standard Deviation 847.809 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 16 | -155.01 mcg/g | Standard Deviation 1142.984 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | Changes in Fecal Calprotectin (CFB) - Exploratory Biomarker | Week 20 | -29.46 mcg/g | Standard Deviation 477.15 |
Other Pre-specified
CRP Changes From Baseline (CFB) (Exploratory)
Change in biomarkers of CRP (C-reactive protein). C-reactive protein (CRP) is a biomarker produced by your liver in response to inflammation. Normal CRP value is below 1 mg/L. 1-3 mg/L is in the yellow zone, indicating some inflammation \>3 mg/L is in the red zone, meaning there is significant inflammation
Time frame: Am 4, Weeks 4, 9, 12, 16, 20, 26; Am 1-3 weeks 4,8,12,16,20, 26
Population: Study participants who received at least one dose of ALTB-168
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Am 4 Week 9, Am 1-3 Week 8 | 6.2 mg/L | Standard Deviation 10.65 |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 16 | NA mg/L | — |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 4 | 6.5 mg/L | Standard Deviation 17.3 |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 20 | NA mg/L | — |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 12 | 6.0 mg/L | Standard Deviation 8.49 |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 26 | NA mg/L | — |
| Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Baseline | 4.3 mg/L | Standard Deviation 5.32 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 26 | -0.42 mg/L | Standard Deviation 4.079 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Baseline | 11.29 mg/L | Standard Deviation 20.555 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 4 | -1.93 mg/L | Standard Deviation 14.403 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Am 4 Week 9, Am 1-3 Week 8 | -0.42 mg/L | Standard Deviation 18.821 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 12 | 0.12 mg/L | Standard Deviation 15.605 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 16 | -0.65 mg/L | Standard Deviation 13.45 |
| Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) | CRP Changes From Baseline (CFB) (Exploratory) | Week 20 | -2.94 mg/L | Standard Deviation 14.161 |