Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, IMU-838, vidofludimus calcium
Brief summary
This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-finding study to evaluate the efficacy and safety of IMU-838 for induction and maintenance therapy with an option for open-label treatment extension in moderate-to-severe ulcerative colitis (CALDOSE-1).
Detailed description
The investigational medicinal product (IMP) IMU-838 (vidofludimus calcium) is a new compound that selectively inhibits the human enzyme dihydroorotate dehydrogenase (DHODH). Dihydroorotate dehydrogenase plays a major role in the de-novo pyrimidine synthesis and is specifically expressed at high levels in proliferating or activated lymphocytes. Resting lymphocytes satisfy their pyrimidine requirements through a DHODH-independent salvage pathway. Thus, IMU-838-mediated DHODH inhibition selectively affects activated, rapidly proliferating lymphocytes. The metabolic stress secondary to DHODH inhibition leads to a reduction of pro-inflammatory cytokine release including interleukin (IL)-17 (IL-17A and IL-17F) and interferon gamma (IFNγ), and to an increased apoptosis in activated lymphocytes. This is a phase 2, multicenter, randomized, double-blind, and placebo-controlled trial in patients with moderate-to-severe UC with an option for open-label treatment extension. The study comprises a blinded induction phase to establish the optimal dose of IMU-838 to induce response and remission, a blinded maintenance phase to evaluate the potential of IMU-838 to maintain remission until Week 50, and an open-label treatment extension arm for all patients who discontinue the blinded phase as scheduled or prematurely, subject to certain restrictions. A subset of patients will undergo a pharmacokinetic (PK) period at the start of the open-label period to establish a full single-dose PK profile.
Interventions
DRUGIMU-838
IMU-838 tablet
DRUGPlacebo
Tablets manufactured to mimic IMU-838 tablets
Sponsors
Immunic AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Induction phase 1. Male and female patients, aged 18 - 80 years 2. UC diagnosed more than 3 months before Screening (Day-30) as documented in the medical chart 3. Previous treatment failure defined as: 1. Patient had an inadequate response with, lost response to, or was intolerant to approved or experimental immunomodulators (azathioprine, 6-mercaptopurine, 6-thioguanine, methotrexate, or tofacitinib) or biologics (no more than 2 treatment failures with biologic drugs i.e. anti-tumor necrosis factor α antibodies \[infliximab, adalimumab, golimumab and their biosimilars\], vedolizumab, or certain experimental antibodies \[ustekinumab\]); or 2. Patient had an inadequate response to, was intolerant to, or is corticosteroid dependent (corticosteroid-dependent patients are defined as i) unable to reduce steroids below the equivalent of prednisolone 10 mg/day within 3 months of starting steroids, without recurrent active disease, or ii) who have a relapse within 3 months of stopping steroids.) 4. Active disease defined as a. Mayo stool frequency score of ≥2 at Screening Visit 1 b. Mayo rectal bleeding score of ≥1 at Screening Visit 1 c. modified Mayo endoscopy subscore of ≥2 at the screening flexible sigmoidoscopy (endoscopy assessed by an independent central reader blinded to screening center and patient information) 5. Endoscopic appearance typical for UC and extending \>15 cm from the anal verge as confirmed by an independent central reader (blinded to screening center and patient information) 6. Laboratory values: Neutrophil count \>1500 cells/µL, platelet count ≥100 000 /mm3, serum creatinine \<1.5 x upper limit of normal (ULN), total bilirubin, alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) \<1.5 x ULN 7. Female patients must: a. Be of non-child-bearing potential i.e. surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before Screening) or post-menopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause), or b. If of child-bearing potential, must have a negative pregnancy test at Screening (blood test) and before the first study drug administration (Day 0 urine test). They must agree not to attempt to become pregnant, must not donate ova, and must use a highly effective contraceptive method 2 months before Screening, during treatment with IMU-838, and at least 3 months after the last dose of study therapy Highly effective forms of birth control are those with a failure rate less than 1% per year and include: \- oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation * oral, injectable, or implantable progestogen-only hormonal contraceptives associated with inhibition of ovulation * intrauterine device or intrauterine hormone-releasing system * bilateral tubal occlusion * vasectomized partner (i.e. the patient's male partner has undergone effective surgical sterilization before the female patient entered the clinical trial and he is the sole sexual partner of the female patient during the clinical trial) * sexual abstinence (acceptable only if it is the patient's usual form of birth control/lifestyle choice) 8. Male patients must agree not to father a child or to donate sperm starting at Screening and throughout the clinical trial and for 3 months after the last dose of study medication. 8. Male patients must also either \- abstain from sexual intercourse with a female partner (acceptable only if it is the patient's usual form of birth control/lifestyle choice), or \- use adequate barrier contraception during treatment with IMU-383 and for at least 3 months after the last dose of study medication For Poland and the UK the following additional requirement apply: * if male patients have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 7 And additionally, for Poland only: * if male patients have a pregnant partner, they must use condoms while taking study medication to avoid exposure of the fetus to study medication 9. Ability to understand and comply with study procedures and restrictions 10. The patient is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study's provisions and has duly signed the informed consent form Maintenance phase 1\. Symptomatic remission achieved at Week 10 or Week 22 of the induction phase Open-label treatment extension arm 1\. Patient is in the induction phase, had received at least 6 weeks of blinded study treatment and completed the sigmoidoscopy (incl. biopsy) regularly scheduled at Week 10/End of Induction, and has neither reached symptomatic remission nor symptomatic response OR Patient is in the extended induction phase, had completed all Week 10 assessments, and has not reached symptomatic remission during or at the end of the extended induction phase, Or Patient is in the maintenance phase and discontinues from the maintenance phase due to symptomatic UC relapse or other reasons with a flexible sigmoidoscopy performed at discontinuation (if the previous sigmoidoscopy had been performed more than 4 weeks before discontinuation) OR Patient has completed the maintenance phase as scheduled (including all Week 50 assessments)
Exclusion criteria
Gastrointestinal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Phase: Symptomatic Remission and Endoscopic Healing at Week 10 | 10 weeks | Composite endpoint: Proportion of patients with both, symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) and endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 10. All patients who were randomized to 30 mg/day and 45 mg/day were used for the assessment of the primary efficacy endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance Phase: Proportion of Patients Without Relapse | 50 weeks | Proportion of patients without symptomatic UC relapse until Week 50 |
| Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10 | 10 weeks | Proportion of patients with both symptomatic remission and endoscopic healing at Week 10 (all individual IMU-838 doses were compared with one another and to placebo) |
| Induction Phase: Symptomatic Remission | 22 weeks | Proportion of patients achieving symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) during the induction phase |
| Induction Phase: Time to Achieving Symptomatic Remission | 22 weeks | Time to achieving symptomatic remission (Mayo rectal bleeding subscore = 0 and Mayo stool frequency subscore of 0 or 1) within the extended induction phase |
| Induction Phase: Proportion of Patients With Clinical Response | 10 weeks | Proportion of patients with clinical response (decrease from Baseline in the full Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1) at Week 10 |
| Induction Phase: Proportion of Patients With Endoscopic Healing | 10 weeks | Proportion of patients with endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 10 |
| Induction Phase: Proportion of Patients With Symptomatic Response | 22 weeks | Proportion of patients with symptomatic response (≥1-point decrease from Baseline in Mayo PRO-2 score) during the induction phase (including extended induction phase) |
| Maintenance Phase: fCP | 50 weeks | Timecourse of biomarker fCP in stool samples |
| Induction Phase: Full Mayo Score | 10 weeks | Change in full Mayo Score from Baseline to Week 10. The full Mayo score is composed of 4 categories (bleeding, stool frequency, physician assessment, and endoscopic appearance) each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 12. A higher score indicates a worse outcome. |
| Induction Phase: Partial Mayo Score | 22 weeks | Change in partial mayo score over 10 or 22 weeks. The partial Mayo score includes only the non-invasive Mayo subscores, ie, stool frequency, rectal bleeding, and physician's global assessment (each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 9). A higher score indicates a worse outcome. |
| Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | 22 weeks | Change in PRO-2 Mayo score over 10 or 22 weeks. Mayo PRO-2 score, ie, stool frequency and rectal bleeding score each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 6. A higher score indicates a worse outcome. |
| Induction Phase: Fecal Calprotectin (fCP) | 22 weeks | Time course of biomarker fCP in stool samples during extended induction phase |
| Induction Phase: C-reactive Protein (CRP) | 22 weeks | Time course of biomarker CRP in blood samples during extended induction phase |
| Safety: Adverse Events | 50 weeks | Incidence and Severity of AEs during the induction and maintenance phases |
| Safety: Number of Participants With Clinically Significant Findings During Physical Examination | 50 weeks | The emergence of any clinically significant findings compared to screening captured during the induction and maintenance phases |
| Safety: Body Weight | 50 weeks | Changes in body weight during the induction and maintenance phases |
| Safety: Blood Pressure | 50 weeks | Changes in blood pressure (mm Hg) during the induction and maintenance phases |
| Safety: Heart Rate | 50 weeks | Changes in heart rate (beats per minute) during the induction and maintenance phases |
| Safety: 12-lead Electrocardiogram (ECG) | 50 weeks | Number of patients with clinically significant changes in ECG |
| Safety: Hematology | up to Week 50 | Number of participants with abnormal hematology laboratory values (treatment-emergent adverse events \[TEAEs\] related to hematological abnormalities) |
| Maintenance Phase: Mayo PRO-2 Score | 50 weeks | Time course of Mayo PRO-2 score until Week 50. Mayo patient-reported outcome score, ie, stool frequency and rectal bleeding score each rated from 0 to 3 3 that are added up to give a total score that ranges from 0 to 6. A higher score indicates a worse outcome. |
| Maintenance Phase: CRP | 50 weeks | Timecourse of biomarker CRP in blood samples |
| Safety: Blood Chemistry | 50 weeks | Number of participants with abnormal blood chemistry laboratory values (TEAES related to clinical chemistry abnormalities) |
| Safety: Coagulation | 10 weeks | Number of participants with clinically significant abnormal coagulation laboratory values |
| Safety: Urinalysis | 50 weeks | Number of participants with abnormal urinalysis laboratory values (TEAEs related to urinalysis) |
| Safety: Micro Ribonucleic Acid-122 Expression | 24 hours | Micro ribonucleic acid-122 (miR-122) expression (before first dose and 24 hours after first dose - foldchange of normalized expression values ) |
| Pharmacodynamics (PK): IMU-838 Trough Level | Day 0, Day 1, Day 7, Week 2 and Week 10 | Measurement of pre-dose (trough) blood plasma levels of IMU-838 throughout the induction period |
| PK: IMU-838 Plasma Level | 2 weeks | Measurement of post-dose blood plasma levels of IMU-838 at Week 2 |
| PK: Area Under the Drug Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC0-24h) | pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose | Single-dose PK measurement of AUC0-24h in a subset of patients in the open-label phase |
| PK: AUC Time Zero to Last Measurable Concentration (AUC0-t) | pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose | Single-dose PK measurement of AUC0-t in a subset of patients in the open-label phase |
| PK: AUC Time Zero to Infinity (AUC0-inf) | pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose | Single-dose PK measurement of AUC0-inf in a subset of patients in the open-label phase |
| PK: Maximum Plasma Concentration (Cmax) | pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose | Single-dose PK measurement of Cmax in a subset of patients in the open-label phase |
| PK: Time to Cmax (Tmax) | pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose | Single-dose PK measurement of Tmax in a subset of patients in the open-label phase |
| Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 14, Week 30, Week 50 | Proportion of patients in symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) by visit up to Week 50 in maintenance phase |
| Maintenance Phase: Proportion of Patients With Endoscopic Healing | 50 weeks | Proportion of patients with endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 50 of maintenance phase |
| Maintenance Phase: Time to Relapse | 50 weeks | Time to symptomatic ulcerative colitis (UC) relapse |
| Maintenance Phase: Corticosteroid-free Remission | 50 weeks | Corticosteroid-free clinical remission (clinical remission and no receipt of systemic or local corticosteroids) at Week 50 in patients receiving corticosteroids at Baseline |
| Open-label Phase: Symptom Control | up to 4 years | Proportion of patients with symptom control |
| Open-label Phase: fCP | Baseline, Week 4 OLE, Week 8 OLE, EoT up to 4 years (variable) | Timecourse of biomarker fCP in stool samples. Visits were scheduled every 4 weeks (+/-7 days) until 50 weeks of total study participation (ie induction + extended induction, if applicable, maintenance + open-label part) and every 10 weeks (+/-7 days) thereafter. The visit schedule in the OLE after 50 weeks of overall study treatment was changed from a 10-week schedule to a 24 week (+/-14 days) schedule after Protocol Version 6.0 came into force. Because the study was terminated early, EoT varied between patients depending on when patients entered the study and the time a patient participated in the induction and maintenance phases before switching to the OLE. |
| Open-label Phase: CRP | Baseline, Week 4 OLE, Week 8 OLE, Week 10 OLE, Week 12 OLE, Week 16 OLE, Week 20 OLE, Week 24 OLE, Week 28 OLE, Week 32 or 38 OLE (depending if entry was after extended induction phase), EoT up to 4 years (variable) | Timecourse of biomarker CRP in blood samples. Visits were scheduled every 4 weeks (+/-7 days) until 50 weeks of total study participation (ie induction + extended induction, if applicable, maintenance + open-label part) and every 10 weeks (+/-7 days) thereafter. The visit schedule in the OLE after 50 weeks of overall study treatment was changed from a 10-week schedule to a 24 week (+/-14 days) schedule after Protocol Version 6.0 came into force. Because the study was terminated early, EoT varied between patients depending on when patients entered the study and the time a patient participated in the induction and maintenance phases before switching to the OLE. |
| Maintenance Phase: Proportion of Patients With Microscopic Healing | 50 weeks | Proportion of patients with microscopic healing (Geboes score of =\< 3.1) at Week 50 of maintenance phase |
Countries
Albania, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czechia, Georgia, Netherlands, North Macedonia, Poland, Portugal, Romania, Russia, Serbia, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study had 3 phases, induction, maintenance and open-label. Patients who achieved symptomatic remission at Week 10 or 22 (extended) of induction phase (IP) could proceed to maintenance phase (MP). Patients who were treated for at least 6 weeks in the induction phase and fulfilled further eligibility criteria could proceed into the open label treatment extension phase (OLE).
Participants by arm
| Arm | Count |
|---|---|
| 10 mg IMU-838 (Induction Phase) Two 5 mg tablets once daily of IMU-838 for 10 to 22 weeks. | 67 |
| 30 mg IMU-838 (Induction Phase) Two 15 mg tablets once daily of IMU-838 for 10 to 22 weeks. | 66 |
| 45 mg IMU-838 (Induction Phase) Two 22.5 mg tablets once daily of IMU-838 for 10 to 22 weeks. | 66 |
| Placebo (Induction Phase) Two tablets once daily for 10 to 22 weeks. | 64 |
| 10 mg IMU-838 (Maintenance Phase Two 5 mg tablets once daily of IMU-838 for up to 50 weeks. | 45 |
| 30 mg IMU-838 (Maintenance Phase) Two 15 mg tablets once daily of IMU-838 for up to 50 weeks. | 40 |
| Placebo (Maintenance Phase) Two tablets once daily for up to 50 weeks. | 27 |
| 30 mg IMU-838 (Open-label Phase) Two 15 mg tablets once daily of IMU-838. | 190 |
| Total | 565 |
Baseline characteristics
| Characteristic | 45 mg IMU-838 (Induction Phase) | 30 mg IMU-838 (Induction Phase) | Placebo (Induction Phase) | 10 mg IMU-838 (Induction Phase) | Total | 10 mg IMU-838 (Maintenance Phase | 30 mg IMU-838 (Maintenance Phase) | Placebo (Maintenance Phase) | 30 mg IMU-838 (Open-label Phase) |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Induction Phase | 40.5 years | 41.0 years | 38.5 years | 40.0 years | 40.0 years | — | — | — | — |
| Age, Continuous Maintenance phase | — | — | — | — | 38.0 years | 37.0 years | 39.5 years | 38.0 years | — |
| Age, Continuous Open-label phase | — | — | — | — | 39.5 years | — | — | — | 39.5 years |
| Current tobacco users Induction phase | 2 Participants | 5 Participants | 4 Participants | 2 Participants | 13 Participants | — | — | — | — |
| Current tobacco users Maintenance phase | — | — | — | — | 1 Participants | 1 Participants | 0 Participants | 0 Participants | — |
| Current tobacco users Open-label phase | — | — | — | — | 10 Participants | — | — | — | 10 Participants |
| Duration of disease | 7.1 years STANDARD_DEVIATION 7.4 | 5.8 years STANDARD_DEVIATION 5.4 | 5.2 years STANDARD_DEVIATION 4.6 | 7.5 years STANDARD_DEVIATION 7.6 | 6.4 years STANDARD_DEVIATION 6.4 | — | — | — | — |
| Ethnicity (NIH/OMB) Induction phase Hispanic or Latino | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 4 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Induction phase Not Hispanic or Latino | 66 Participants | 65 Participants | 61 Participants | 67 Participants | 259 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Induction phase Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Maintenance phase Hispanic or Latino | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Ethnicity (NIH/OMB) Maintenance phase Not Hispanic or Latino | — | — | — | — | 112 Participants | 45 Participants | 40 Participants | 27 Participants | — |
| Ethnicity (NIH/OMB) Maintenance phase Unknown or Not Reported | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Ethnicity (NIH/OMB) Open-label phase Hispanic or Latino | — | — | — | — | 3 Participants | — | — | — | 3 Participants |
| Ethnicity (NIH/OMB) Open-label phase Not Hispanic or Latino | — | — | — | — | 187 Participants | — | — | — | 187 Participants |
| Ethnicity (NIH/OMB) Open-label phase Unknown or Not Reported | — | — | — | — | 0 Participants | — | — | — | 0 Participants |
| Mayo PRO-2 Score at Basline Induction phase | 4.3 units on a scale STANDARD_DEVIATION 1 | 4.3 units on a scale STANDARD_DEVIATION 1 | 4.3 units on a scale STANDARD_DEVIATION 0.9 | 4.1 units on a scale STANDARD_DEVIATION 1.2 | 4.2 units on a scale STANDARD_DEVIATION 1 | — | — | — | — |
| Mayo PRO-2 Score at Basline Maintenance phase | — | — | — | — | 0.8 units on a scale STANDARD_DEVIATION 0.6 | 0.8 units on a scale STANDARD_DEVIATION 0.5 | 0.9 units on a scale STANDARD_DEVIATION 0.8 | 0.7 units on a scale STANDARD_DEVIATION 0.5 | — |
| Mayo PRO-2 Score at Basline Open-label phase (Entry in open label after induction phase) | — | — | — | — | 3.9 units on a scale STANDARD_DEVIATION 1.2 | — | — | — | 3.9 units on a scale STANDARD_DEVIATION 1.2 |
| Mayo PRO-2 Score at Basline Open-label phase (Entry in open label after maintenance phase) | — | — | — | — | 1.6 units on a scale STANDARD_DEVIATION 1.7 | — | — | — | 1.6 units on a scale STANDARD_DEVIATION 1.7 |
| Race (NIH/OMB) Induction phase American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Induction phase Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | — | — | — | — |
| Race (NIH/OMB) Induction phase Black or African American | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | — | — | — | — |
| Race (NIH/OMB) Induction phase More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | — | — | — | — |
| Race (NIH/OMB) Induction phase Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Induction phase Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Induction phase White | 64 Participants | 66 Participants | 64 Participants | 64 Participants | 258 Participants | — | — | — | — |
| Race (NIH/OMB) Maintenance phase American Indian or Alaska Native | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Maintenance phase Asian | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Maintenance phase Black or African American | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Maintenance phase More than one race | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Maintenance phase Native Hawaiian or Other Pacific Islander | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Maintenance phase Unknown or Not Reported | — | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Maintenance phase White | — | — | — | — | 112 Participants | 45 Participants | 40 Participants | 27 Participants | — |
| Race (NIH/OMB) Open-label phase American Indian or Alaska Native | — | — | — | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) Open-label phase Asian | — | — | — | — | 1 Participants | — | — | — | 1 Participants |
| Race (NIH/OMB) Open-label phase Black or African American | — | — | — | — | 1 Participants | — | — | — | 1 Participants |
| Race (NIH/OMB) Open-label phase More than one race | — | — | — | — | 1 Participants | — | — | — | 1 Participants |
| Race (NIH/OMB) Open-label phase Native Hawaiian or Other Pacific Islander | — | — | — | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) Open-label phase Unknown or Not Reported | — | — | — | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) Open-label phase White | — | — | — | — | 187 Participants | — | — | — | 187 Participants |
| Region of Enrollment Albania | 3 participants | 2 participants | 5 participants | 3 participants | 13 participants | 0 participants | 4 participants | 3 participants | 2 participants |
| Region of Enrollment Belarus | 2 participants | 1 participants | 0 participants | 3 participants | 6 participants | 2 participants | 2 participants | 0 participants | 4 participants |
| Region of Enrollment Bosnia and Herzegovina | 2 participants | 2 participants | 0 participants | 1 participants | 5 participants | 4 participants | 1 participants | 0 participants | 3 participants |
| Region of Enrollment Bulgaria | 1 participants | 0 participants | 1 participants | 1 participants | 3 participants | 0 participants | 0 participants | 1 participants | 3 participants |
| Region of Enrollment Croatia | 3 participants | 2 participants | 0 participants | 0 participants | 5 participants | 0 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment Czechia | 3 participants | 1 participants | 1 participants | 4 participants | 9 participants | 0 participants | 1 participants | 1 participants | 9 participants |
| Region of Enrollment Netherlands | 2 participants | 0 participants | 1 participants | 1 participants | 4 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment North Macedonia | 2 participants | 2 participants | 1 participants | 5 participants | 10 participants | 1 participants | 1 participants | 0 participants | 6 participants |
| Region of Enrollment Poland | 12 participants | 20 participants | 12 participants | 11 participants | 55 participants | 9 participants | 9 participants | 4 participants | 42 participants |
| Region of Enrollment Portugal | 0 participants | 1 participants | 1 participants | 0 participants | 2 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Romania | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Russia | 10 participants | 5 participants | 8 participants | 3 participants | 26 participants | 4 participants | 4 participants | 1 participants | 20 participants |
| Region of Enrollment Serbia | 5 participants | 4 participants | 2 participants | 5 participants | 16 participants | 4 participants | 4 participants | 0 participants | 11 participants |
| Region of Enrollment Spain | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Ukraine | 18 participants | 21 participants | 25 participants | 21 participants | 85 participants | 20 participants | 14 participants | 14 participants | 66 participants |
| Region of Enrollment United Kingdom | 0 participants | 2 participants | 4 participants | 4 participants | 10 participants | 1 participants | 0 participants | 2 participants | 9 participants |
| Region of Enrollment United States | 1 participants | 3 participants | 3 participants | 5 participants | 12 participants | 0 participants | 0 participants | 0 participants | 8 participants |
| Sex: Female, Male Induction phase Female | 26 Participants | 26 Participants | 31 Participants | 32 Participants | 115 Participants | — | — | — | — |
| Sex: Female, Male Induction phase Male | 40 Participants | 40 Participants | 33 Participants | 35 Participants | 148 Participants | — | — | — | — |
| Sex: Female, Male Maintenance phase Female | — | — | — | — | 49 Participants | 15 Participants | 25 Participants | 9 Participants | — |
| Sex: Female, Male Maintenance phase Male | — | — | — | — | 63 Participants | 30 Participants | 15 Participants | 18 Participants | — |
| Sex: Female, Male Open-label phase Female | — | — | — | — | 83 Participants | — | — | — | 83 Participants |
| Sex: Female, Male Open-label phase Male | — | — | — | — | 107 Participants | — | — | — | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 67 | 0 / 66 | 0 / 63 | 0 / 45 | 0 / 40 | 0 / 27 | 0 / 190 |
| other Total, other adverse events | 8 / 67 | 7 / 67 | 12 / 66 | 13 / 63 | 7 / 45 | 6 / 40 | 2 / 27 | 24 / 190 |
| serious Total, serious adverse events | 2 / 67 | 5 / 67 | 5 / 66 | 0 / 63 | 3 / 45 | 2 / 40 | 1 / 27 | 14 / 190 |
Outcome results
Primary
Induction Phase: Symptomatic Remission and Endoscopic Healing at Week 10
Composite endpoint: Proportion of patients with both, symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) and endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 10. All patients who were randomized to 30 mg/day and 45 mg/day were used for the assessment of the primary efficacy endpoint
Time frame: 10 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Symptomatic Remission and Endoscopic Healing at Week 10 | 16 Participants |
| Placebo (Induction Phase) | Induction Phase: Symptomatic Remission and Endoscopic Healing at Week 10 | 8 Participants |
p-value: 0.5836Cochran-Mantel-Haenszel
Secondary
Induction Phase: C-reactive Protein (CRP)
Time course of biomarker CRP in blood samples during extended induction phase
Time frame: 22 weeks
Population: FAS
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (all patients) | 3.50 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 10 (all patients) | 3.40 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (Only patients who entered extended induction phase) | 3.65 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 22 (Only patients who entered extended induction phase) | 2.70 mg/L |
| Placebo (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (all patients) | 3.2 mg/L |
| Placebo (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 22 (Only patients who entered extended induction phase) | 1.25 mg/L |
| Placebo (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 10 (all patients) | 1.85 mg/L |
| Placebo (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (Only patients who entered extended induction phase) | 2.40 mg/L |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 22 (Only patients who entered extended induction phase) | 2.80 mg/L |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 10 (all patients) | 4.00 mg/L |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (Only patients who entered extended induction phase) | 5.55 mg/L |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (all patients) | 5.30 mg/L |
| Placebo (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (all patients) | 3.70 mg/L |
| Placebo (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 10 (all patients) | 3.50 mg/L |
| Placebo (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 22 (Only patients who entered extended induction phase) | 2.00 mg/L |
| Placebo (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (Only patients who entered extended induction phase) | 3.05 mg/L |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 22 (Only patients who entered extended induction phase) | 2.75 mg/L |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (Only patients who entered extended induction phase) | 7.85 mg/L |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Week 10 (all patients) | 2.75 mg/L |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: C-reactive Protein (CRP) | Day 0 (all patients) | 3.50 mg/L |
Secondary
Induction Phase: Fecal Calprotectin (fCP)
Time course of biomarker fCP in stool samples during extended induction phase
Time frame: 22 weeks
Population: FAS
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (all patients) | 799.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 10 (all patients | 290.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (Only patients who entered extended induction phase) | 616.5 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 22 (Only patients who entered extended induction phase) | 332.0 mg/kg |
| Placebo (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (all patients) | 899.0 mg/kg |
| Placebo (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 22 (Only patients who entered extended induction phase) | 387.0 mg/kg |
| Placebo (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 10 (all patients | 405.0 mg/kg |
| Placebo (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (Only patients who entered extended induction phase) | 1039.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 22 (Only patients who entered extended induction phase) | 353.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 10 (all patients | 384.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (Only patients who entered extended induction phase) | 603.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (all patients) | 697.0 mg/kg |
| Placebo (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (all patients) | 711.5 mg/kg |
| Placebo (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 10 (all patients | 301.5 mg/kg |
| Placebo (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 22 (Only patients who entered extended induction phase) | 314.0 mg/kg |
| Placebo (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (Only patients who entered extended induction phase) | 547.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 22 (Only patients who entered extended induction phase) | 576.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (Only patients who entered extended induction phase) | 856.5 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Week 10 (all patients | 265.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Fecal Calprotectin (fCP) | Day 0 (all patients) | 992.0 mg/kg |
Secondary
Induction Phase: Full Mayo Score
Change in full Mayo Score from Baseline to Week 10. The full Mayo score is composed of 4 categories (bleeding, stool frequency, physician assessment, and endoscopic appearance) each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 12. A higher score indicates a worse outcome.
Time frame: 10 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Full Mayo Score | Baseline | 9.1 score on a scale | Standard Deviation 1.4 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Full Mayo Score | Change from Baseline to Week 10 | -2.6 score on a scale | Standard Deviation 2.7 |
| Placebo (Induction Phase) | Induction Phase: Full Mayo Score | Baseline | 9.1 score on a scale | Standard Deviation 1.4 |
| Placebo (Induction Phase) | Induction Phase: Full Mayo Score | Change from Baseline to Week 10 | -2.3 score on a scale | Standard Deviation 2.7 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Full Mayo Score | Baseline | 9.0 score on a scale | Standard Deviation 1.6 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Full Mayo Score | Change from Baseline to Week 10 | -3.0 score on a scale | Standard Deviation 2.6 |
| Placebo (Induction Phase) | Induction Phase: Full Mayo Score | Change from Baseline to Week 10 | -2.5 score on a scale | Standard Deviation 2.7 |
| Placebo (Induction Phase) | Induction Phase: Full Mayo Score | Baseline | 9.1 score on a scale | Standard Deviation 1.4 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Full Mayo Score | Baseline | 9.1 score on a scale | Standard Deviation 1.4 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Full Mayo Score | Change from Baseline to Week 10 | -2.8 score on a scale | Standard Deviation 2.7 |
Secondary
Induction Phase: Partial Mayo Score
Change in partial mayo score over 10 or 22 weeks. The partial Mayo score includes only the non-invasive Mayo subscores, ie, stool frequency, rectal bleeding, and physician's global assessment (each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 9). A higher score indicates a worse outcome.
Time frame: 22 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (all patients) | 6.6 score on a scale | Standard Deviation 1.2 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 10 (all patients) | -2.2 score on a scale | Standard Deviation 2.2 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (only patients who entered extended induction phase) | 6.6 score on a scale | Standard Deviation 1.2 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -3.5 score on a scale | Standard Deviation 2.1 |
| Placebo (Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (all patients) | 6.5 score on a scale | Standard Deviation 1.1 |
| Placebo (Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -3.6 score on a scale | Standard Deviation 2.2 |
| Placebo (Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 10 (all patients) | -1.9 score on a scale | Standard Deviation 2.2 |
| Placebo (Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (only patients who entered extended induction phase) | 6.5 score on a scale | Standard Deviation 1 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -3.4 score on a scale | Standard Deviation 2.3 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 10 (all patients) | -2.4 score on a scale | Standard Deviation 2.2 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (only patients who entered extended induction phase) | 6.6 score on a scale | Standard Deviation 1.3 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (all patients) | 6.4 score on a scale | Standard Deviation 1.4 |
| Placebo (Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (all patients) | 6.5 score on a scale | Standard Deviation 1.2 |
| Placebo (Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 10 (all patients) | -1.9 score on a scale | Standard Deviation 2 |
| Placebo (Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -3.7 score on a scale | Standard Deviation 2.2 |
| Placebo (Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (only patients who entered extended induction phase) | 6.6 score on a scale | Standard Deviation 1.2 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -3.3 score on a scale | Standard Deviation 2 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (only patients who entered extended induction phase) | 6.7 score on a scale | Standard Deviation 1.2 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Partial Mayo Score | Change from Baseline to Week 10 (all patients) | -2.4 score on a scale | Standard Deviation 2.3 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Partial Mayo Score | Baseline (all patients) | 6.6 score on a scale | Standard Deviation 1.2 |
Secondary
Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score
Change in PRO-2 Mayo score over 10 or 22 weeks. Mayo PRO-2 score, ie, stool frequency and rectal bleeding score each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 6. A higher score indicates a worse outcome.
Time frame: 22 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (all patients) | 4.3 score on a scale | Standard Deviation 1 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 10 (all patients) | -1.6 score on a scale | Standard Deviation 1.7 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (only patients who entered extended induction phase) | 4.3 score on a scale | Standard Deviation 1 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -2.5 score on a scale | Standard Deviation 1.6 |
| Placebo (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (all patients) | 4.3 score on a scale | Standard Deviation 0.9 |
| Placebo (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -2.6 score on a scale | Standard Deviation 1.6 |
| Placebo (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 10 (all patients) | -1.4 score on a scale | Standard Deviation 1.7 |
| Placebo (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (only patients who entered extended induction phase) | 4.3 score on a scale | Standard Deviation 0.8 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -2.4 score on a scale | Standard Deviation 1.8 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 10 (all patients) | -1.7 score on a scale | Standard Deviation 1.6 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (only patients who entered extended induction phase) | 4.2 score on a scale | Standard Deviation 1.1 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (all patients) | 4.1 score on a scale | Standard Deviation 1.2 |
| Placebo (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (all patients) | 4.3 score on a scale | Standard Deviation 1 |
| Placebo (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 10 (all patients) | -1.4 score on a scale | Standard Deviation 1.6 |
| Placebo (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -2.7 score on a scale | Standard Deviation 1.6 |
| Placebo (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (only patients who entered extended induction phase) | 4.3 score on a scale | Standard Deviation 1.1 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 22 (only patients who entered extended induction phase) | -2.3 score on a scale | Standard Deviation 1.6 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (only patients who entered extended induction phase) | 4.3 score on a scale | Standard Deviation 1 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Change from Baseline to Week 10 (all patients) | -1.8 score on a scale | Standard Deviation 1.7 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score | Baseline (all patients) | 4.3 score on a scale | Standard Deviation 1 |
Secondary
Induction Phase: Proportion of Patients With Clinical Response
Proportion of patients with clinical response (decrease from Baseline in the full Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1) at Week 10
Time frame: 10 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Proportion of Patients With Clinical Response | 50 Participants |
| Placebo (Induction Phase) | Induction Phase: Proportion of Patients With Clinical Response | 27 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Proportion of Patients With Clinical Response | 31 Participants |
| Placebo (Induction Phase) | Induction Phase: Proportion of Patients With Clinical Response | 23 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Proportion of Patients With Clinical Response | 27 Participants |
Secondary
Induction Phase: Proportion of Patients With Endoscopic Healing
Proportion of patients with endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 10
Time frame: 10 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Proportion of Patients With Endoscopic Healing | 28 Participants |
| Placebo (Induction Phase) | Induction Phase: Proportion of Patients With Endoscopic Healing | 12 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Proportion of Patients With Endoscopic Healing | 18 Participants |
| Placebo (Induction Phase) | Induction Phase: Proportion of Patients With Endoscopic Healing | 14 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Proportion of Patients With Endoscopic Healing | 14 Participants |
Secondary
Induction Phase: Proportion of Patients With Symptomatic Response
Proportion of patients with symptomatic response (≥1-point decrease from Baseline in Mayo PRO-2 score) during the induction phase (including extended induction phase)
Time frame: 22 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Proportion of Patients With Symptomatic Response | 101 Participants |
| Placebo (Induction Phase) | Induction Phase: Proportion of Patients With Symptomatic Response | 49 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Proportion of Patients With Symptomatic Response | 55 Participants |
| Placebo (Induction Phase) | Induction Phase: Proportion of Patients With Symptomatic Response | 52 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Proportion of Patients With Symptomatic Response | 49 Participants |
Secondary
Induction Phase: Symptomatic Remission
Proportion of patients achieving symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) during the induction phase
Time frame: 22 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Symptomatic Remission | 56 Participants |
| Placebo (Induction Phase) | Induction Phase: Symptomatic Remission | 28 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Symptomatic Remission | 38 Participants |
| Placebo (Induction Phase) | Induction Phase: Symptomatic Remission | 25 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Symptomatic Remission | 31 Participants |
Secondary
Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10
Proportion of patients with both symptomatic remission and endoscopic healing at Week 10 (all individual IMU-838 doses were compared with one another and to placebo)
Time frame: 10 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10 | 10 Participants |
| Placebo (Induction Phase) | Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10 | 7 Participants |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10 | 9 Participants |
| Placebo (Induction Phase) | Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10 | 8 Participants |
Secondary
Induction Phase: Time to Achieving Symptomatic Remission
Time to achieving symptomatic remission (Mayo rectal bleeding subscore = 0 and Mayo stool frequency subscore of 0 or 1) within the extended induction phase
Time frame: 22 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Induction Phase: Time to Achieving Symptomatic Remission | 108.8 days | Standard Error 5.5 |
| Placebo (Induction Phase) | Induction Phase: Time to Achieving Symptomatic Remission | 119.6 days | Standard Error 7.1 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Time to Achieving Symptomatic Remission | 98 days | Standard Error 7.7 |
| Placebo (Induction Phase) | Induction Phase: Time to Achieving Symptomatic Remission | 115.9 days | Standard Error 7.4 |
| 45 mg IMU-838 (Induction Phase) | Induction Phase: Time to Achieving Symptomatic Remission | 101.9 days | Standard Error 8.1 |
Secondary
Maintenance Phase: Corticosteroid-free Remission
Corticosteroid-free clinical remission (clinical remission and no receipt of systemic or local corticosteroids) at Week 50 in patients receiving corticosteroids at Baseline
Time frame: 50 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Corticosteroid-free Remission | 10 Participants |
| Placebo (Induction Phase) | Maintenance Phase: Corticosteroid-free Remission | 16 Participants |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Corticosteroid-free Remission | 5 Participants |
Secondary
Maintenance Phase: CRP
Timecourse of biomarker CRP in blood samples
Time frame: 50 weeks
Population: FAS
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: CRP | Maintenance phase Baseline | 1.30 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: CRP | Week 14 | 1.10 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: CRP | Week 30 | 1.30 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: CRP | Week 50 | 1.10 mg/L |
| Placebo (Induction Phase) | Maintenance Phase: CRP | Week 50 | 3.60 mg/L |
| Placebo (Induction Phase) | Maintenance Phase: CRP | Maintenance phase Baseline | 2.50 mg/L |
| Placebo (Induction Phase) | Maintenance Phase: CRP | Week 30 | 2.05 mg/L |
| Placebo (Induction Phase) | Maintenance Phase: CRP | Week 14 | 1.50 mg/L |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: CRP | Week 50 | 1.95 mg/L |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: CRP | Week 14 | 1.90 mg/L |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: CRP | Week 30 | 1.00 mg/L |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: CRP | Maintenance phase Baseline | 1.10 mg/L |
Secondary
Maintenance Phase: fCP
Timecourse of biomarker fCP in stool samples
Time frame: 50 weeks
Population: FAS
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: fCP | Maintenance phase Baseline | 256.5 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: fCP | Week 14 | 99.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: fCP | Week 30 | 149.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: fCP | Week 50 | 181.0 mg/kg |
| Placebo (Induction Phase) | Maintenance Phase: fCP | Week 50 | 147.0 mg/kg |
| Placebo (Induction Phase) | Maintenance Phase: fCP | Maintenance phase Baseline | 207.0 mg/kg |
| Placebo (Induction Phase) | Maintenance Phase: fCP | Week 30 | 217.0 mg/kg |
| Placebo (Induction Phase) | Maintenance Phase: fCP | Week 14 | 145.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: fCP | Week 50 | 364.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: fCP | Week 14 | 353.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: fCP | Week 30 | 210.0 mg/kg |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: fCP | Maintenance phase Baseline | 335.0 mg/kg |
Secondary
Maintenance Phase: Mayo PRO-2 Score
Time course of Mayo PRO-2 score until Week 50. Mayo patient-reported outcome score, ie, stool frequency and rectal bleeding score each rated from 0 to 3 3 that are added up to give a total score that ranges from 0 to 6. A higher score indicates a worse outcome.
Time frame: 50 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Mayo PRO-2 Score | Maintenance phase Baseline | 0.8 score on a scale | Standard Deviation 0.5 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Mayo PRO-2 Score | Change from Baseline to Week 50 | 0.1 score on a scale | Standard Deviation 0.9 |
| Placebo (Induction Phase) | Maintenance Phase: Mayo PRO-2 Score | Maintenance phase Baseline | 0.9 score on a scale | Standard Deviation 0.8 |
| Placebo (Induction Phase) | Maintenance Phase: Mayo PRO-2 Score | Change from Baseline to Week 50 | 0.2 score on a scale | Standard Deviation 1.1 |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Mayo PRO-2 Score | Maintenance phase Baseline | 0.7 score on a scale | Standard Deviation 0.5 |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Mayo PRO-2 Score | Change from Baseline to Week 50 | 0.4 score on a scale | Standard Deviation 0.9 |
Secondary
Maintenance Phase: Proportion of Patients in Symptomatic Remission
Proportion of patients in symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) by visit up to Week 50 in maintenance phase
Time frame: Week 14, Week 30, Week 50
Population: FAS
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 14 | 16 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 50 | 27 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 30 | 33 Participants |
| Placebo (Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 30 | 23 Participants |
| Placebo (Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 14 | 14 Participants |
| Placebo (Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 50 | 24 Participants |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 50 | 16 Participants |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 14 | 7 Participants |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Proportion of Patients in Symptomatic Remission | Week 30 | 19 Participants |
Secondary
Maintenance Phase: Proportion of Patients With Endoscopic Healing
Proportion of patients with endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 50 of maintenance phase
Time frame: 50 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Proportion of Patients With Endoscopic Healing | 15 Participants |
| Placebo (Induction Phase) | Maintenance Phase: Proportion of Patients With Endoscopic Healing | 19 Participants |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Proportion of Patients With Endoscopic Healing | 6 Participants |
Secondary
Maintenance Phase: Proportion of Patients With Microscopic Healing
Proportion of patients with microscopic healing (Geboes score of =\< 3.1) at Week 50 of maintenance phase
Time frame: 50 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Proportion of Patients With Microscopic Healing | 25 Participants |
| Placebo (Induction Phase) | Maintenance Phase: Proportion of Patients With Microscopic Healing | 20 Participants |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Proportion of Patients With Microscopic Healing | 12 Participants |
Secondary
Maintenance Phase: Proportion of Patients Without Relapse
Proportion of patients without symptomatic UC relapse until Week 50
Time frame: 50 weeks
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Proportion of Patients Without Relapse | 32 Participants |
| Placebo (Induction Phase) | Maintenance Phase: Proportion of Patients Without Relapse | 24 Participants |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Proportion of Patients Without Relapse | 18 Participants |
Secondary
Maintenance Phase: Time to Relapse
Time to symptomatic ulcerative colitis (UC) relapse
Time frame: 50 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Maintenance Phase: Time to Relapse | 231.7 days | Standard Error 10 |
| Placebo (Induction Phase) | Maintenance Phase: Time to Relapse | 221.9 days | Standard Error 16.2 |
| 45 mg IMU-838 (Induction Phase) | Maintenance Phase: Time to Relapse | 186.6 days | Standard Error 10.2 |
Secondary
Open-label Phase: CRP
Timecourse of biomarker CRP in blood samples. Visits were scheduled every 4 weeks (+/-7 days) until 50 weeks of total study participation (ie induction + extended induction, if applicable, maintenance + open-label part) and every 10 weeks (+/-7 days) thereafter. The visit schedule in the OLE after 50 weeks of overall study treatment was changed from a 10-week schedule to a 24 week (+/-14 days) schedule after Protocol Version 6.0 came into force. Because the study was terminated early, EoT varied between patients depending on when patients entered the study and the time a patient participated in the induction and maintenance phases before switching to the OLE.
Time frame: Baseline, Week 4 OLE, Week 8 OLE, Week 10 OLE, Week 12 OLE, Week 16 OLE, Week 20 OLE, Week 24 OLE, Week 28 OLE, Week 32 or 38 OLE (depending if entry was after extended induction phase), EoT up to 4 years (variable)
Population: FAS, separated by entry in OLE, data only shown if number of patients included in analysis ≥ 50 per visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Baseline | 5.20 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Visit 1 (Week 4 OLE) | 3.30 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Visit 2 (Week 8 OLE) | 2.30 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Visit 3 (Week 12 OLE) | 2.40 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Visit 4 (Week 16 OLE) | 2.60 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Visit 5 (Week 20 OLE) | 3.60 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Visit 6 (Week 24 OLE) | 3.40 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Visit 7 (Week 28 OLE) | 2.80 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - Visit 8 (Week 32 or 38 OLE) | 2.20 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after (extended) induction phase - end of treatment (up to 4 years, variable) | 2.45 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after maintenance phase - Baseline | 1.90 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after maintenance phase - Visit 1 (Week 10 OLE) | 1.55 mg/L |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: CRP | Entry in OLE after maintenance phase - Visit 2 (Week 20 OLE) | 1.25 mg/L |
Secondary
Open-label Phase: fCP
Timecourse of biomarker fCP in stool samples. Visits were scheduled every 4 weeks (+/-7 days) until 50 weeks of total study participation (ie induction + extended induction, if applicable, maintenance + open-label part) and every 10 weeks (+/-7 days) thereafter. The visit schedule in the OLE after 50 weeks of overall study treatment was changed from a 10-week schedule to a 24 week (+/-14 days) schedule after Protocol Version 6.0 came into force. Because the study was terminated early, EoT varied between patients depending on when patients entered the study and the time a patient participated in the induction and maintenance phases before switching to the OLE.
Time frame: Baseline, Week 4 OLE, Week 8 OLE, EoT up to 4 years (variable)
Population: FAS, separated by entry in OLE, data only shown if number of patients included in analysis ≥ 5 per visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: fCP | Entry in OLE after (extended) induction phase - Baseline | 542.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: fCP | Entry in OLE after (extended) induction phase - Visit 1 (Week 4 OLE) | 557.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: fCP | Entry in OLE after (extended) induction phase - Visit 2 (Week 8 OLE) | 467.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: fCP | Entry in OLE after (extended) induction phase - end of treatment (up to 4 years, variable) | 234.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: fCP | Entry in OLE after maintenance phase - Baseline | 221.0 mg/kg |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: fCP | Entry in OLE after maintenance phase - end of treatment (up to 4 years, variable) | 168.0 mg/kg |
Secondary
Open-label Phase: Symptom Control
Proportion of patients with symptom control
Time frame: up to 4 years
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Open-label Phase: Symptom Control | 55 Participants |
Secondary
Pharmacodynamics (PK): IMU-838 Trough Level
Measurement of pre-dose (trough) blood plasma levels of IMU-838 throughout the induction period
Time frame: Day 0, Day 1, Day 7, Week 2 and Week 10
Population: SAF
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Week 2 | 0.97 µg/mL |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 7 | 0.58 µg/mL |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 0 | 0.00 µg/mL |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 1 | 0.30 µg/mL |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Week 10 | 1.17 µg/mL |
| Placebo (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 7 | 1.71 µg/mL |
| Placebo (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 0 | 0.00 µg/mL |
| Placebo (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 1 | 0.94 µg/mL |
| Placebo (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Week 2 | 3.24 µg/mL |
| Placebo (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Week 10 | 3.32 µg/mL |
| 45 mg IMU-838 (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Week 10 | 5.03 µg/mL |
| 45 mg IMU-838 (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Week 2 | 5.23 µg/mL |
| 45 mg IMU-838 (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 0 | 0.00 µg/mL |
| 45 mg IMU-838 (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 7 | 2.77 µg/mL |
| 45 mg IMU-838 (Induction Phase) | Pharmacodynamics (PK): IMU-838 Trough Level | Day 1 | 1.41 µg/mL |
Secondary
PK: Area Under the Drug Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC0-24h)
Single-dose PK measurement of AUC0-24h in a subset of patients in the open-label phase
Time frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose
Population: No data were collected for this endpoint.
Secondary
PK: AUC Time Zero to Infinity (AUC0-inf)
Single-dose PK measurement of AUC0-inf in a subset of patients in the open-label phase
Time frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose
Population: No data were collected for this endpoint.
Secondary
PK: AUC Time Zero to Last Measurable Concentration (AUC0-t)
Single-dose PK measurement of AUC0-t in a subset of patients in the open-label phase
Time frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose
Population: No data were collected for this endpoint.
Secondary
PK: IMU-838 Plasma Level
Measurement of post-dose blood plasma levels of IMU-838 at Week 2
Time frame: 2 weeks
Population: SAF
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | PK: IMU-838 Plasma Level | 2.30 µg/mL |
| Placebo (Induction Phase) | PK: IMU-838 Plasma Level | 6.05 µg/mL |
| 45 mg IMU-838 (Induction Phase) | PK: IMU-838 Plasma Level | 10.70 µg/mL |
Secondary
PK: Maximum Plasma Concentration (Cmax)
Single-dose PK measurement of Cmax in a subset of patients in the open-label phase
Time frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose
Population: No data were collected for this endpoint.
Secondary
PK: Time to Cmax (Tmax)
Single-dose PK measurement of Tmax in a subset of patients in the open-label phase
Time frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose
Population: No data were collected for this endpoint.
Secondary
Safety: 12-lead Electrocardiogram (ECG)
Number of patients with clinically significant changes in ECG
Time frame: 50 weeks
Population: SAF
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: 12-lead Electrocardiogram (ECG) | 0 Participants |
| Placebo (Induction Phase) | Safety: 12-lead Electrocardiogram (ECG) | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: 12-lead Electrocardiogram (ECG) | 0 Participants |
| Placebo (Induction Phase) | Safety: 12-lead Electrocardiogram (ECG) | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: 12-lead Electrocardiogram (ECG) | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: 12-lead Electrocardiogram (ECG) | 0 Participants |
| Placebo (Maintenance Phase) | Safety: 12-lead Electrocardiogram (ECG) | 0 Participants |
Secondary
Safety: Adverse Events
Incidence and Severity of AEs during the induction and maintenance phases
Time frame: 50 weeks
Population: SAF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Adverse Events | Any TEAE | 28 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Adverse Events | Any mild TEAE | 23 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Adverse Events | Any moderate TEAE | 7 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Adverse Events | Any severe TEAE | 2 Participants |
| Placebo (Induction Phase) | Safety: Adverse Events | Any severe TEAE | 3 Participants |
| Placebo (Induction Phase) | Safety: Adverse Events | Any moderate TEAE | 10 Participants |
| Placebo (Induction Phase) | Safety: Adverse Events | Any TEAE | 30 Participants |
| Placebo (Induction Phase) | Safety: Adverse Events | Any mild TEAE | 21 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Adverse Events | Any moderate TEAE | 11 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Adverse Events | Any mild TEAE | 24 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Adverse Events | Any TEAE | 30 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Adverse Events | Any severe TEAE | 2 Participants |
| Placebo (Induction Phase) | Safety: Adverse Events | Any TEAE | 23 Participants |
| Placebo (Induction Phase) | Safety: Adverse Events | Any mild TEAE | 15 Participants |
| Placebo (Induction Phase) | Safety: Adverse Events | Any moderate TEAE | 13 Participants |
| Placebo (Induction Phase) | Safety: Adverse Events | Any severe TEAE | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Adverse Events | Any TEAE | 16 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Adverse Events | Any severe TEAE | 2 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Adverse Events | Any mild TEAE | 11 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Adverse Events | Any moderate TEAE | 5 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Adverse Events | Any mild TEAE | 12 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Adverse Events | Any TEAE | 16 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Adverse Events | Any moderate TEAE | 7 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Adverse Events | Any severe TEAE | 2 Participants |
| Placebo (Maintenance Phase) | Safety: Adverse Events | Any moderate TEAE | 4 Participants |
| Placebo (Maintenance Phase) | Safety: Adverse Events | Any TEAE | 12 Participants |
| Placebo (Maintenance Phase) | Safety: Adverse Events | Any mild TEAE | 8 Participants |
| Placebo (Maintenance Phase) | Safety: Adverse Events | Any severe TEAE | 0 Participants |
Secondary
Safety: Blood Chemistry
Number of participants with abnormal blood chemistry laboratory values (TEAES related to clinical chemistry abnormalities)
Time frame: 50 weeks
Population: SAF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood creatinine increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Hypokalemia | 1 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood cholesterol increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Hyperlipasemia | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Liver function test abnormal | 1 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood bilirubin unconjugated increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Alanine transferase increased | 2 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood calcium decreased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Hypophosphatasemia | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | C-reactive protein increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Aspartate aminotransferase increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Hyperkalemia | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood triglycerides increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Hyperbilirubinemia | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Lipase increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Hypertriglyceridemia | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood potassium increased | 1 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Fecal calprotectin increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase increased | 1 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Hyperuricemia | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Gamma-glutamyltransferase increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Amylase increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase MB increased | 1 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Blood bilirubin increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Chemistry | Hepatic enzyme increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Gamma-glutamyltransferase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hyperkalemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hepatic enzyme increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hyperbilirubinemia | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Aspartate aminotransferase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Alanine transferase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood bilirubin increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Liver function test abnormal | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood bilirubin unconjugated increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hypophosphatasemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood calcium decreased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood cholesterol increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hypokalemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood creatinine increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase MB increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hyperuricemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase increased | 2 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Amylase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood potassium increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hypertriglyceridemia | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood triglycerides increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | C-reactive protein increased | 2 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hyperlipasemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Fecal calprotectin increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Lipase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hyperlipasemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood creatinine increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Lipase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hyperuricemia | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Liver function test abnormal | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hepatic enzyme increased | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase MB increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood bilirubin increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Aspartate aminotransferase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hyperkalemia | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hypertriglyceridemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood potassium increased | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Amylase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Fecal calprotectin increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hyperbilirubinemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hypophosphatasemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood triglycerides increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood bilirubin unconjugated increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood calcium decreased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hypokalemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Alanine transferase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Gamma-glutamyltransferase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood cholesterol increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | C-reactive protein increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hepatic enzyme increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | C-reactive protein increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Lipase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood creatinine increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood calcium decreased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hyperuricemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hypokalemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Fecal calprotectin increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood bilirubin increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood triglycerides increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase MB increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Liver function test abnormal | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Amylase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Aspartate aminotransferase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hypophosphatasemia | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Gamma-glutamyltransferase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Alanine transferase increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hyperlipasemia | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hypertriglyceridemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood bilirubin unconjugated increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hyperbilirubinemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Hyperkalemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood cholesterol increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Blood Chemistry | Blood potassium increased | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hyperlipasemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Alanine transferase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Amylase increased | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Aspartate aminotransferase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood bilirubin increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood bilirubin unconjugated increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood calcium decreased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood cholesterol increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood creatinine increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase MB increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood potassium increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Blood triglycerides increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | C-reactive protein increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Fecal calprotectin increased | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Gamma-glutamyltransferase increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hepatic enzyme increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hyperbilirubinemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hyperkalemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hypertriglyceridemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hyperuricemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hypokalemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Hypophosphatasemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Liver function test abnormal | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Chemistry | Lipase increased | 1 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood cholesterol increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood calcium decreased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Alanine transferase increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Hypokalemia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Amylase increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Hypertriglyceridemia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood bilirubin unconjugated increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood triglycerides increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Hypophosphatasemia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Hyperlipasemia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase MB increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood bilirubin increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Hyperkalemia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Aspartate aminotransferase increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Lipase increased | 1 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Liver function test abnormal | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood creatinine increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | C-reactive protein increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Hyperbilirubinemia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Hyperuricemia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Hepatic enzyme increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Blood potassium increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Gamma-glutamyltransferase increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Chemistry | Fecal calprotectin increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Fecal calprotectin increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Hyperkalemia | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | C-reactive protein increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood triglycerides increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Hyperlipasemia | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood potassium increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase increased | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Hypertriglyceridemia | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood creatine phosphokinase MB increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood creatinine increased | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Alanine transferase increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Hyperuricemia | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood cholesterol increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood calcium decreased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Hypokalemia | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood bilirubin unconjugated increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Lipase increased | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Hypophosphatasemia | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Blood bilirubin increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Aspartate aminotransferase increased | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Liver function test abnormal | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Hepatic enzyme increased | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Hyperbilirubinemia | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Gamma-glutamyltransferase increased | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Blood Chemistry | Amylase increased | 0 Participants |
Secondary
Safety: Blood Pressure
Changes in blood pressure (mm Hg) during the induction and maintenance phases
Time frame: 50 weeks
Population: SAF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Pressure | Induction phase - Week 10 (systolic blood pressure) | 123.1 mmHg | Standard Deviation 11.4 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Pressure | Induction phase - Week 10 (diastolic blood pressure) | 76.1 mmHg | Standard Deviation 9.1 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Pressure | Induction phase - Day 0 (systolic blood pressure) | 123.2 mmHg | Standard Deviation 14.2 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Pressure | Induction phase - Day 0 (diastolic blood pressure) | 76.2 mmHg | Standard Deviation 10.8 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Pressure | Induction phase - Week 22 (systolic blood pressure) | 118.3 mmHg | Standard Deviation 10.2 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Blood Pressure | Induction phase - Week 22 (diastolic blood pressure) | 72.0 mmHg | Standard Deviation 7.6 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 22 (systolic blood pressure) | 126.7 mmHg | Standard Deviation 12.3 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Day 0 (diastolic blood pressure) | 78.1 mmHg | Standard Deviation 10.3 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 22 (diastolic blood pressure) | 77.6 mmHg | Standard Deviation 7.4 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 10 (systolic blood pressure) | 123.8 mmHg | Standard Deviation 13.2 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 10 (diastolic blood pressure) | 79.5 mmHg | Standard Deviation 9.2 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Day 0 (systolic blood pressure) | 125.1 mmHg | Standard Deviation 12.8 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 22 (systolic blood pressure) | 119.8 mmHg | Standard Deviation 6.6 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Induction phase - Day 0 (systolic blood pressure) | 123.2 mmHg | Standard Deviation 11.4 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 10 (systolic blood pressure) | 121.7 mmHg | Standard Deviation 9.7 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 22 (diastolic blood pressure) | 75.4 mmHg | Standard Deviation 6.5 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Induction phase - Day 0 (diastolic blood pressure) | 79.5 mmHg | Standard Deviation 9.4 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 10 (diastolic blood pressure) | 77.3 mmHg | Standard Deviation 7.9 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 22 (systolic blood pressure) | 121.8 mmHg | Standard Deviation 12.3 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 10 (systolic blood pressure) | 122.0 mmHg | Standard Deviation 12.8 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 22 (diastolic blood pressure) | 74.2 mmHg | Standard Deviation 9.8 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Week 10 (diastolic blood pressure) | 75.5 mmHg | Standard Deviation 7.9 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Day 0 (systolic blood pressure) | 121.9 mmHg | Standard Deviation 11.8 |
| Placebo (Induction Phase) | Safety: Blood Pressure | Induction phase - Day 0 (diastolic blood pressure) | 74.9 mmHg | Standard Deviation 8.2 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Maintenance phase - Week 50 (diastolic blood pressure | 76.5 mmHg | Standard Deviation 9.9 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Maintenance phase - baseline (systolic blood pressure) | 121.3 mmHg | Standard Deviation 10.6 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Maintenance phase - Week 50 (systolic blood pressure) | 122.0 mmHg | Standard Deviation 13 |
| 45 mg IMU-838 (Induction Phase) | Safety: Blood Pressure | Maintenance phase - baseline (diastolic blood pressure) | 75.2 mmHg | Standard Deviation 8.7 |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Pressure | Maintenance phase - baseline (systolic blood pressure) | 123.7 mmHg | Standard Deviation 12.2 |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Pressure | Maintenance phase - Week 50 (systolic blood pressure) | 125.3 mmHg | Standard Deviation 14.3 |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Pressure | Maintenance phase - Week 50 (diastolic blood pressure | 77.1 mmHg | Standard Deviation 9 |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Blood Pressure | Maintenance phase - baseline (diastolic blood pressure) | 76.5 mmHg | Standard Deviation 9.5 |
| Placebo (Maintenance Phase) | Safety: Blood Pressure | Maintenance phase - baseline (systolic blood pressure) | 124.1 mmHg | Standard Deviation 13 |
| Placebo (Maintenance Phase) | Safety: Blood Pressure | Maintenance phase - baseline (diastolic blood pressure) | 75.1 mmHg | Standard Deviation 8.8 |
| Placebo (Maintenance Phase) | Safety: Blood Pressure | Maintenance phase - Week 50 (diastolic blood pressure | 74.7 mmHg | Standard Deviation 6.4 |
| Placebo (Maintenance Phase) | Safety: Blood Pressure | Maintenance phase - Week 50 (systolic blood pressure) | 122.6 mmHg | Standard Deviation 9.2 |
Secondary
Safety: Body Weight
Changes in body weight during the induction and maintenance phases
Time frame: 50 weeks
Population: SAF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Body Weight | Induction phase - Week 22 | 70.310 kg | Standard Deviation 13.64 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Body Weight | Induction phase - Week 10 | 73.747 kg | Standard Deviation 20.03 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Body Weight | Induction phase - Day 0 | 73.881 kg | Standard Deviation 19.479 |
| Placebo (Induction Phase) | Safety: Body Weight | Induction phase - Week 22 | 74.689 kg | Standard Deviation 15.143 |
| Placebo (Induction Phase) | Safety: Body Weight | Induction phase - Day 0 | 72.436 kg | Standard Deviation 15.348 |
| Placebo (Induction Phase) | Safety: Body Weight | Induction phase - Week 10 | 71.457 kg | Standard Deviation 14.522 |
| 45 mg IMU-838 (Induction Phase) | Safety: Body Weight | Induction phase - Week 10 | 75.094 kg | Standard Deviation 14.148 |
| 45 mg IMU-838 (Induction Phase) | Safety: Body Weight | Induction phase - Day 0 | 73.959 kg | Standard Deviation 13.915 |
| 45 mg IMU-838 (Induction Phase) | Safety: Body Weight | Induction phase - Week 22 | 75.188 kg | Standard Deviation 18.202 |
| Placebo (Induction Phase) | Safety: Body Weight | Induction phase - Week 10 | 71.437 kg | Standard Deviation 15.998 |
| Placebo (Induction Phase) | Safety: Body Weight | Induction phase - Day 0 | 70.141 kg | Standard Deviation 15.754 |
| Placebo (Induction Phase) | Safety: Body Weight | Induction phase - Week 22 | 69.635 kg | Standard Deviation 14.425 |
| 45 mg IMU-838 (Induction Phase) | Safety: Body Weight | Maintenance phase - Baseline | 74.431 kg | Standard Deviation 13.081 |
| 45 mg IMU-838 (Induction Phase) | Safety: Body Weight | Maintenance phase - Week 50 | 75.743 kg | Standard Deviation 13.452 |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Body Weight | Maintenance phase - Week 50 | 73.986 kg | Standard Deviation 18.069 |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Body Weight | Maintenance phase - Baseline | 70.490 kg | Standard Deviation 16.48 |
| Placebo (Maintenance Phase) | Safety: Body Weight | Maintenance phase - Baseline | 72.441 kg | Standard Deviation 13.259 |
| Placebo (Maintenance Phase) | Safety: Body Weight | Maintenance phase - Week 50 | 70.310 kg | Standard Deviation 11.458 |
Secondary
Safety: Coagulation
Number of participants with clinically significant abnormal coagulation laboratory values
Time frame: 10 weeks
Population: SAF, Coagulation parameters were only analyzed in the Induction phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Coagulation | 0 Participants |
| Placebo (Induction Phase) | Safety: Coagulation | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Coagulation | 0 Participants |
| Placebo (Induction Phase) | Safety: Coagulation | 0 Participants |
Secondary
Safety: Heart Rate
Changes in heart rate (beats per minute) during the induction and maintenance phases
Time frame: 50 weeks
Population: SAF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Heart Rate | Induction phase - Week 10 | 76.1 beats per minute | Standard Deviation 13.9 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Heart Rate | Induction phase - Day 0 | 74.7 beats per minute | Standard Deviation 13.6 |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Heart Rate | Induction phase - Week 22 | 69.6 beats per minute | Standard Deviation 13 |
| Placebo (Induction Phase) | Safety: Heart Rate | Induction phase - Week 10 | 74.1 beats per minute | Standard Deviation 10.4 |
| Placebo (Induction Phase) | Safety: Heart Rate | Induction phase - Week 22 | 71.9 beats per minute | Standard Deviation 9.1 |
| Placebo (Induction Phase) | Safety: Heart Rate | Induction phase - Day 0 | 77.4 beats per minute | Standard Deviation 12.3 |
| 45 mg IMU-838 (Induction Phase) | Safety: Heart Rate | Induction phase - Week 10 | 73.6 beats per minute | Standard Deviation 9 |
| 45 mg IMU-838 (Induction Phase) | Safety: Heart Rate | Induction phase - Week 22 | 71.6 beats per minute | Standard Deviation 6.2 |
| 45 mg IMU-838 (Induction Phase) | Safety: Heart Rate | Induction phase - Day 0 | 73.6 beats per minute | Standard Deviation 8.9 |
| Placebo (Induction Phase) | Safety: Heart Rate | Induction phase - Week 10 | 73.9 beats per minute | Standard Deviation 10.8 |
| Placebo (Induction Phase) | Safety: Heart Rate | Induction phase - Day 0 | 73.5 beats per minute | Standard Deviation 9 |
| Placebo (Induction Phase) | Safety: Heart Rate | Induction phase - Week 22 | 70.8 beats per minute | Standard Deviation 7.1 |
| 45 mg IMU-838 (Induction Phase) | Safety: Heart Rate | Maintenance phase - Week 50 | 73.0 beats per minute | Standard Deviation 8.6 |
| 45 mg IMU-838 (Induction Phase) | Safety: Heart Rate | Maintenance phase -Baseline | 73.0 beats per minute | Standard Deviation 9.2 |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Heart Rate | Maintenance phase - Week 50 | 73.2 beats per minute | Standard Deviation 6.5 |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Heart Rate | Maintenance phase -Baseline | 73.4 beats per minute | Standard Deviation 7.5 |
| Placebo (Maintenance Phase) | Safety: Heart Rate | Maintenance phase -Baseline | 72.4 beats per minute | Standard Deviation 9.7 |
| Placebo (Maintenance Phase) | Safety: Heart Rate | Maintenance phase - Week 50 | 75.4 beats per minute | Standard Deviation 10.7 |
Secondary
Safety: Hematology
Number of participants with abnormal hematology laboratory values (treatment-emergent adverse events \[TEAEs\] related to hematological abnormalities)
Time frame: up to Week 50
Population: SAF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Leukocytosis | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Anemia | 3 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Neutropenia | 1 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Platelet count increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | White blood cell count increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Hemoglobin decreased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Neutrophil count increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Microcytic anemia | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Thrombocytosis | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Hematology | Leukopenia | 1 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Microcytic anemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Neutrophil count increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Leukopenia | 1 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Leukocytosis | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Neutropenia | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Thrombocytosis | 1 Participants |
| Placebo (Induction Phase) | Safety: Hematology | White blood cell count increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Hemoglobin decreased | 2 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Platelet count increased | 1 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Anemia | 6 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Neutrophil count increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Leukopenia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Hemoglobin decreased | 9 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Thrombocytosis | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Microcytic anemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | White blood cell count increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Platelet count increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Neutropenia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Anemia | 4 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Leukocytosis | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Neutropenia | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Leukocytosis | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Thrombocytosis | 1 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Neutrophil count increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Microcytic anemia | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Hemoglobin decreased | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Anemia | 3 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Platelet count increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | White blood cell count increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Hematology | Leukopenia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Leukocytosis | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Platelet count increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Anemia | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Leukopenia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Hemoglobin decreased | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Thrombocytosis | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Neutropenia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Microcytic anemia | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | Neutrophil count increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Hematology | White blood cell count increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Neutrophil count increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Anemia | 2 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Leukopenia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Neutropenia | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Thrombocytosis | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Hemoglobin decreased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Platelet count increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Leukocytosis | 1 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | Microcytic anemia | 1 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Hematology | White blood cell count increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Leukocytosis | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Platelet count increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Neutrophil count increased | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Hemoglobin decreased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Thrombocytosis | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Neutropenia | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Leukopenia | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Anemia | 2 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | White blood cell count increased | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Hematology | Microcytic anemia | 0 Participants |
Secondary
Safety: Micro Ribonucleic Acid-122 Expression
Micro ribonucleic acid-122 (miR-122) expression (before first dose and 24 hours after first dose - foldchange of normalized expression values )
Time frame: 24 hours
Population: SAF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Micro Ribonucleic Acid-122 Expression | 2.0276 fold change | Standard Deviation 2.7747 |
| Placebo (Induction Phase) | Safety: Micro Ribonucleic Acid-122 Expression | 3.5573 fold change | Standard Deviation 10.8852 |
| 45 mg IMU-838 (Induction Phase) | Safety: Micro Ribonucleic Acid-122 Expression | 1.8842 fold change | Standard Deviation 3.5346 |
| Placebo (Induction Phase) | Safety: Micro Ribonucleic Acid-122 Expression | 2.5739 fold change | Standard Deviation 5.2723 |
Secondary
Safety: Number of Participants With Clinically Significant Findings During Physical Examination
The emergence of any clinically significant findings compared to screening captured during the induction and maintenance phases
Time frame: 50 weeks
Population: SAF
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Number of Participants With Clinically Significant Findings During Physical Examination | 0 Participants |
| Placebo (Induction Phase) | Safety: Number of Participants With Clinically Significant Findings During Physical Examination | 3 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Number of Participants With Clinically Significant Findings During Physical Examination | 4 Participants |
| Placebo (Induction Phase) | Safety: Number of Participants With Clinically Significant Findings During Physical Examination | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Number of Participants With Clinically Significant Findings During Physical Examination | 2 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Number of Participants With Clinically Significant Findings During Physical Examination | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Number of Participants With Clinically Significant Findings During Physical Examination | 2 Participants |
Secondary
Safety: Urinalysis
Number of participants with abnormal urinalysis laboratory values (TEAEs related to urinalysis)
Time frame: 50 weeks
Population: SAF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Ketonuria | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Renal Cyst | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Hyperuricosuria | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Red blood cells urine positive | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Blood urine present | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Renal colic | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Creatinine urine increased | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Hematuria | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Crystalluria | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Proteinuria | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Micturition urgency | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Hemorrhage urinary tract | 0 Participants |
| Combined IMU-838 (30 or 45 mg IMU-838, Induction Phase) | Safety: Urinalysis | Hyperoxaluria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Renal colic | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Ketonuria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Creatinine urine increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Hemorrhage urinary tract | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Red blood cells urine positive | 1 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Proteinuria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Crystalluria | 2 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Hematuria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Hyperoxaluria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Renal Cyst | 1 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Hyperuricosuria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Micturition urgency | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Blood urine present | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Renal colic | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Ketonuria | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Red blood cells urine positive | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Micturition urgency | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Hyperoxaluria | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Creatinine urine increased | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Blood urine present | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Hyperuricosuria | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Proteinuria | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Renal Cyst | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Hemorrhage urinary tract | 1 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Hematuria | 5 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Crystalluria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Ketonuria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Blood urine present | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Creatinine urine increased | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Crystalluria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Hematuria | 1 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Hemorrhage urinary tract | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Hyperoxaluria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Hyperuricosuria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Micturition urgency | 1 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Proteinuria | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Red blood cells urine positive | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Renal colic | 0 Participants |
| Placebo (Induction Phase) | Safety: Urinalysis | Renal Cyst | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Ketonuria | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Blood urine present | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Crystalluria | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Red blood cells urine positive | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Hemorrhage urinary tract | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Renal Cyst | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Creatinine urine increased | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Proteinuria | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Hyperoxaluria | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Hyperuricosuria | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Hematuria | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Renal colic | 0 Participants |
| 45 mg IMU-838 (Induction Phase) | Safety: Urinalysis | Micturition urgency | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Hyperuricosuria | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Hemorrhage urinary tract | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Crystalluria | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Ketonuria | 1 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Hematuria | 2 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Micturition urgency | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Creatinine urine increased | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Red blood cells urine positive | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Blood urine present | 1 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Renal Cyst | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Renal colic | 0 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Proteinuria | 1 Participants |
| 30 mg IMU-838 (Maintenance Phase) | Safety: Urinalysis | Hyperoxaluria | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Micturition urgency | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Proteinuria | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Hematuria | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Crystalluria | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Ketonuria | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Renal colic | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Hemorrhage urinary tract | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Blood urine present | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Renal Cyst | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Creatinine urine increased | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Hyperoxaluria | 0 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Red blood cells urine positive | 1 Participants |
| Placebo (Maintenance Phase) | Safety: Urinalysis | Hyperuricosuria | 0 Participants |