A Phase 2 interventional study of ALTB-168 in Ulcerative Colitis, sponsored by AltruBio Inc.. Terminated at 12 sites in 2 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-01-05.
Sponsored by AltruBio Inc. · Phase 2, Interventional, and Treatment
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.
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.
Moderate-to-severe active UC, at time of screening, defined as:
Stable doses of concomitant medications, including :
Exclusion Criteria:
GI related exclusion criteria:
Short gut syndrome
General health related exclusion criteria:
History of drug abuse according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria within 12 months prior to screening or positive drug screening tests.
Infection related exclusion criteria:
intravenous doses of ALTB-168
Biological: ALTB-168
monoclonal antibody
Also known as: Neihulizumab
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
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
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
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
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
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
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
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
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
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
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
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.
| Milestone | ALTB-168 in Patients With Refractory Ulcerative Colitis |
|---|---|
| Started | 24 |
| Number of participants who received 8 doses of altb-168 | 10 |
| Number of participants who received 10 doses of altb-168 | 14 |
| Completed | 11 |
| Not completed | 13 |
| Withdrew: Lack of efficacy | 4 |
| Withdrew: Withdrawal by subject | 7 |
| Withdrew: Adverse event | 1 |
| Withdrew: Disease relapse | 1 |
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.
| percentage of total number of patients | Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) |
|---|---|---|
| The Proportion of Patients With Clinical Response at Week 12 | 22.2 (2.8 to 60) | 50 (23 to 77) |
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.
| percentage of total number of patients | Pilot Study (Amendment 1~3: 9 mg/kg; Total 8 Doses) | Main Study (Amendment 4: 9 mg/kg; Total 10 Doses) |
|---|---|---|
| Clinical Response at week 6 | 33.3 (7.5 to 70.1) | 57.1 (28.9 to 82.3) |
| Clinical Response at week 16 | 0 (0 to 0) | 64.3 (35.1 to 87.2) |
| Clinical Response at week 20 | 11.1 (0.3 to 48.2) | 64.3 (35.1 to 87.2) |
| Clinical Response at week 26 | 11.1 (0.3 to 48.2) | 35.7 (12.8 to 64.9) |
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.
| percentage of total number of patients | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Clinical response at week 6 | 11.1 (0.3 to 48.2) | 35.7 (12.8 to 64.9) |
| Clinical response at week 16 | 0 (0 to 0) | 35.7 (12.8 to 64.9) |
| Clinical response at week 20 | 0 (0 to 0) | 35.7 (12.8 to 64.9) |
| Clinical response at week 26 | 11.1 (0.3 to 48.2) | 21.4 (4.7 to 50.8) |
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.
| score on a scale | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Flexible Sigmoidoscopy Score at Baseline | 2.7 ± 0.5 | 2.6 ± 0.5 |
| Flexible Sigmoidoscopy Score at week 12 CFB | -0.7 ± 1.03 | -0.6 ± 1.0 |
| Flexible Sigmoidoscopy Score at week 26 CFB | 0 ± 0 | -0.6 ± 1.27 |
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.
| participants | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Week 12 | 2 | 4 |
| Week 26 | 0 | 3 |
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
| participants | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Week 12 | 0 | 2 |
| Week 26 | 1 | 4 |
The histological healing is defined as histological grade = 0
| Participants | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Week 12 | 0 | 0 |
| Week 26 | 0 | 0 |
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.
| participants | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Week 12 | 2 | 9 |
| Week 26 | 1 | 7 |
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.
| participants | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Week 12 | 2 | 9 |
| Week 26 | 1 | 7 |
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
| mg/L | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Baseline | 4.3 ± 5.32 | 11.29 ± 20.555 |
| Week 4 | 6.5 ± 17.30 | -1.93 ± 14.403 |
| Am 4 Week 9, Am 1-3 Week 8 | 6.2 ± 10.65 | -0.42 ± 18.821 |
| Week 12 | 6.0 ± 8.49 | 0.12 ± 15.605 |
| Week 16 | NA ± NA | -0.65 ± 13.450 |
| Week 20 | NA ± NA | -2.94 ± 14.161 |
| Week 26 | NA ± NA | -0.42 ± 4.079 |
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.
| mcg/g | Amendment 1~3: 9 mg/kg; Total 8 Doses | Amendment 4: 9 mg/kg; Total 10 Doses |
|---|---|---|
| Baseline | 682.80 ± 548.153 | 1283.49 ± 758.019 |
| Week 4 (CFB) | 113.89 ± 753.179 | -203.30 ± 704.559 |
| Week 9 (Am 4, week 8 Am 1-3) | 223.17 ± 605.971 | -384.47 ± 662.420 |
| Week 12 | 923.00 ± 997.162 | -584.17 ± 847.809 |
| Week 16 | NA ± NA | -155.01 ± 1142.984 |
| Week 20 | NA ± NA | -29.46 ± 477.150 |
| Week 26 | NA ± NA | -780.30 ± 633.292 |
Collected over 26 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ALTB-168 9mg/kg (Amendment 1-3) | 0/10 (0%) | 1/10 (10%) | 9/10 (90%) |
| ALTB-168 9mg/kg (Amendment 4) | 0/14 (0%) | 0/14 (0%) | 13/14 (92.9%) |
| Event | ALTB-168 9mg/kg (Amendment 1-3) | ALTB-168 9mg/kg (Amendment 4) |
|---|---|---|
| Ulcerative Colitis FlareGastrointestinal disorders | 1/10 | 0/14 |
| Event | ALTB-168 9mg/kg (Amendment 1-3) | ALTB-168 9mg/kg (Amendment 4) |
|---|---|---|
| HeadacheNervous system disorders | 5/10 | 5/14 |
| Abdominal PainGastrointestinal disorders | 0/10 | 3/14 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/10 | 1/14 |
| ConfusionInjury, poisoning and procedural complications | 0/10 | 2/14 |
| Fecal Calprotectin IncreasedInvestigations | 0/10 | 2/14 |
| RashSkin and subcutaneous tissue disorders | 0/10 | 2/14 |
| NasopharyngitisInfections and infestations | 0/10 | 2/14 |
| ConstipationGastrointestinal disorders | 1/10 | 0/14 |
| ChillsGeneral disorders | 1/10 | 0/14 |
| FatigueGeneral disorders | 1/10 | 0/14 |
Safety population /The mITT set was defined as all patients who were enrolled and who received at least one dose of ALTB-168 treatment.
| Age, Categorical(Participants) | ALTB-168 |
|---|---|
| Enrolled Under Amendment 1-3 — <=18 years | 0 |
| Enrolled Under Amendment 1-3 — Between 18 and 65 years | 9 |
| Enrolled Under Amendment 1-3 — >=65 years | 1 |
| Enrolled Under Amendment 4 — <=18 years | 0 |
| Enrolled Under Amendment 4 — Between 18 and 65 years | 14 |
| Enrolled Under Amendment 4 — >=65 years | 0 |
| Age, Continuous(years) | ALTB-168 |
|---|---|
| Amendment 1-3 | 37 (21 to 65) |
| Amendment 4 | 35.5 (22 to 61) |
| Sex: Female, Male(Participants) | ALTB-168 |
|---|---|
| Enrolled under Amendment 1~3 — Female | 6 |
| Enrolled under Amendment 1~3 — Male | 4 |
| Enrolled under Amendment 4 — Female | 7 |
| Enrolled under Amendment 4 — Male | 7 |
| Race/Ethnicity, Customized(Participants) | ALTB-168 |
|---|---|
| Ethnicity — Hispanic or Latino | 7 |
| Ethnicity — Not Hispanic or Latino | 15 |
| Ethnicity — Not reported | 2 |
| Region of Enrollment(participants) | ALTB-168 |
|---|---|
| United States | 24 |
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