Ulcerative ColitisPhase 1NCT03943550
Double-Blinded, Placebo-Controlled Phase 1b Study for Safety, PK, Efficacy, PD of RO7049665 in Participants With Ulcerative Colitis (UC)
A Phase 1 study testing RO7049665 in people with Ulcerative Colitis, run by Hoffmann-La Roche at 6 sites in 5 countries.
Trial summary
The principal aim of this study is to evaluate the safety and tolerability of RO7049665 in participants with active ulcerative colitis (UC). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- RO7049665
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 6 sitesin 5 countries
- Study dates
- 13 May 2019to 22 Jul 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with UC for at least 12 weeks prior to screening
- Screening colonoscopy for colorectal cancer conducted within the prior two years if a history of pancolitis with disease duration ≥ 8 years or history of left-sided colitis and disease duration ≥12 years
- Evidence of disease activity at time of screening
- Insufficient clinical response to standard of care (SOC) therapy or intolerance to SOC
Who cannot join
- Diagnosis of Crohn's disease or indeterminate colitis
- History of infection with hepatitis B, human immunodeficiency virus (HIV), active hepatitis C virus (HCV) infection, or other chronic infection
- Active infections requiring systemic therapy with antibiotic, antiviral or antifungal or febrile illness within 7 days before Day -1
- History of primary or acquired immunodeficiency
- Abnormal hematologic values
- Abnormal hepatic enzyme or hepatic function values
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
Hungary2 sites
Drug Research Centre Gyogyszervizsgalo Kozpontot Kft.
Balatonfüred, 8230
SE ÁOK I. sz. Belgyógyászati Klinika
Budapest, 1083
United States1 site
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
Moldova1 site
ARENSIA Phase 1 Unit- Spitalul Clinic Republican Location
Chisinau, MD-2025
Ukraine1 site
Medical center of Yuriy Spizhenko LLC
Kapitanovka Village, KIEV Governorate, 08112
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo Controlled Phase Ib Study to Investigate the Safety, Tolerability, Pharmacokinetics, Preliminary Efficacy, and Pharmacodynamics of Subcutaneously Administered RO7049665 in Participants With Active Ulcerative Colitis
The principal aim of this study is to evaluate the safety and tolerability of RO7049665 in participants with active ulcerative colitis (UC).
- Conditions
- Ulcerative Colitis
- Being tested
- RO7049665, Placebo
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO7049665Drug
Multiple ascending doses of RO7049665 will be administered SC.
PlaceboDrug
Matching placebo will be administered SC.
| Study group | Role | What they receive |
|---|---|---|
| RO7049665 | Experimental | Participants will receive a subcutaneous (SC) dose of RO7049665 every 2 weeks for 4 doses. Receives: Drug: RO7049665 |
| Placebo | Placebo comparator | Participants will receive a SC dose of matching placebo every 2 weeks for 4 doses. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect. Severity of AEs were graded according to NCI CTCAE v4.0.
Measured: From baseline up to safety follow-up visit on Day 99
Secondary outcomes (14)
Time to Maximum Concentration (Tmax) of RO7049665
Measured: Day 1 to Day 15 (predose) and Day 43 (post-dose)
Maximum Serum Concentration Observed (Cmax) of RO7049665
Measured: Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665
Measured: Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES)
The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy (i.e., centrally read MCS-ES) and Physician Global Assessment (PGA). Flexible sigmoidoscopy (or colonoscopy) was centrally read and scored using the MCS-ES scoring systems. The disease was considered as endoscopic normal or inactive if the MCS-ES (centrally read) was 0, mild (erythema, decreased vascular pattern) if MCS-ES was 1, moderate (marked erythema, absent vascular pattern, erosions) if MCS-ES was 2 and severe (spontaneous bleeding, ulceration) if MCS-ES was 3. The Endoscopy Subscore of the Mayo Score was modified so that a value of 1 did not include friability. A negative change from baseline indicates improvement.
Measured: Baseline, Days 29 and 57
Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
Flexible sigmoidoscopy (or colonoscopy) were centrally read and scored using the UCEIS scoring systems. The UCEIS total score is a sum of 3 assessments: Bleeding (scored 0-3), Erosion and Ulcers (scored 0-3), and Vascular Pattern (scored 0-2). The total score ranges from 0-8, with higher score indicating more severe disease. A negative change from baseline indicates improvement.
Measured: Baseline, Days 29 and 57
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS)
Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 centimeters (cm) from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using GS. The GS is a stepwise grading system used for the evaluation of microscopic inflammation and histopathologic disease activity in UC. The microscopic appearance of the mucosa is categorized into 6 grades: Grade 0: architectural changes, Grade 1: chronic inflammatory infiltrate, Grade 2: lamina propria neutrophils and eosinophils, Grade 3: neutrophils in epithelium, Grade 4: crypt destruction and erosions or Grade 5: ulcerations, and each grade of the score is divided in 4 subcategories. A decrease of the Geboes grading system to Grades 0 or 1 would indicate mucosal healing.
Measured: Baseline, Days 29 and 57
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI)
Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 cm from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using RIH. The RHI is an evaluative index, derived from the Geboes score and is designed to be reproducible and responsive to clinically meaningful change in disease activity over time. The total RHI score ranges from 0 (no disease activity) to 33 (severe disease activity). A negative change from baseline indicates improvement.
Measured: Baseline, Days 29 and 57
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI)
Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 cm from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using NHI. NHI is a validated index for assessing histological disease activity in UC. It is composed of three histological items defining five grades of disease activity: absence of significant histological disease (Grade 0), chronic inflammatory infiltrate with no acute inflammatory infiltrate (Grade 1), mildly active disease (Grade 2), moderately active disease (Grade 3), and severely active disease (Grade 4). The presence of ulceration on the biopsy specimen corresponds to severely active disease (Grade 4). A decrease of the NHI grading system to Grades 0 or 1 would indicate improvement.
Measured: Baseline, Days 29 and 57
Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response
The MCS ranges from 0 to 12 and is a composite of 4 assessments: stool frequency, rectal bleeding, endoscopy (i.e., centrally read MCS-ES) and Physician Global Assessment (PGA). Each assessment was rated from 0-3, with higher score indicating more severe disease. Clinical response was defined as a decrease in the MCS of at least 3 points and at least 30% decrease from baseline.
Measured: Baseline, Days 29 and 57
Number of Participants With Anti-Drug Antibodies (ADAs)
ADA assays was used to detect anti-drug antibodies against RO7049665. Samples which were positive for anti-drug antibodies were further assessed using a neutralizing antibody assay. Participants were considered ADA positive if they were ADA negative at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 4-fold (treatment-enhanced ADA response).
Measured: Baseline; Post-dose on Days 8, 22, 57, 71 and 99; Pre-dose on Days 15, 29 and 43
Change From Baseline in White Blood Cells (Tregs, Teffs)
Measured: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Change From Baseline in White Blood Cells (Natural Killer (NK) Cells)
Measured: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Change From Baseline in White Blood Cells (B Cells)
Measured: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Change From Baseline in Eosinophils
Measured: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 8, 22, 36, 57, 71 and follow-up visit on Day 99
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start13 May 2019
- Primary completion22 Jul 2021
- Study completion22 Jul 2021
Why it stopped: The decision to terminate study WP40161 was based on that treatment with RO7049665 showed trends in efficacy, however these data were below expectations and would not have supported superiority over standard of care.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03943550
- Sponsor's protocol ID
- WP40161
- Other IDs
- 2017-004599-74, 2017
- Status last verified
- Jun 2023
- First submitted
- 7 May 2019
- Last updated
- 15 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo Controlled Phase Ib Study to Investigate the Safety, Tolerability, Pharmacokinetics, Preliminary Efficacy, and Pharmacodynamics of Subcutaneously Administered RO7049665 in Participants With Active Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT03943550
- Acronym / sponsor ID
- WP40161
- Conditions
- Ulcerative Colitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The decision to terminate study WP40161 was based on that treatment with RO7049665 showed trends in efficacy, however these data were below expectations and would not have supported superiority over standard of care.
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 13 May 2019 (actual)
- Primary completion
- 22 Jul 2021 (actual)
- Study completion
- 22 Jul 2021 (actual)
- First posted
- 9 May 2019 (actual)
- Results
- Posted 15 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The principal aim of this study is to evaluate the safety and tolerability of RO7049665 in participants with active ulcerative colitis (UC).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RO7049665 | Experimental | Drug: RO7049665Participants will receive a subcutaneous (SC) dose of RO7049665 every 2 weeks for 4 doses. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive a SC dose of matching placebo every 2 weeks for 4 doses. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosed with UC for at least 12 weeks prior to screening
- Screening colonoscopy for colorectal cancer conducted within the prior two years if a history of pancolitis with disease duration ≥ 8 years or history of left-sided colitis and disease duration ≥12 years
- Evidence of disease activity at time of screening
- Insufficient clinical response to standard of care (SOC) therapy or intolerance to SOC
Key exclusion criteria (6 listed)
- Diagnosis of Crohn's disease or indeterminate colitis
- History of infection with hepatitis B, human immunodeficiency virus (HIV), active hepatitis C virus (HCV) infection, or other chronic infection
- Active infections requiring systemic therapy with antibiotic, antiviral or antifungal or febrile illness within 7 days before Day -1
- History of primary or acquired immunodeficiency
- Abnormal hematologic values
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RO7049665Multiple ascending doses of RO7049665 will be administered SC. | Drug | RO7049665 |
| PlaceboMatching placebo will be administered SC. | Drug | Placebo |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From baseline up to safety follow-up visit on Day 99
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect. Severity of AEs were graded according to NCI CTCAE v4.0.
14 secondary outcomes
Time to Maximum Concentration (Tmax) of RO7049665
Time frame: Day 1 to Day 15 (predose) and Day 43 (post-dose)
Maximum Serum Concentration Observed (Cmax) of RO7049665
Time frame: Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665
Time frame: Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES)
Time frame: Baseline, Days 29 and 57
Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
Time frame: Baseline, Days 29 and 57
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS)
Time frame: Baseline, Days 29 and 57
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI)
Time frame: Baseline, Days 29 and 57
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI)
Time frame: Baseline, Days 29 and 57
Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response
Time frame: Baseline, Days 29 and 57
Number of Participants With Anti-Drug Antibodies (ADAs)
Time frame: Baseline; Post-dose on Days 8, 22, 57, 71 and 99; Pre-dose on Days 15, 29 and 43
Change From Baseline in White Blood Cells (Tregs, Teffs)
Time frame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Change From Baseline in White Blood Cells (Natural Killer (NK) Cells)
Time frame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Change From Baseline in White Blood Cells (B Cells)
Time frame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Change From Baseline in Eosinophils
Time frame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 8, 22, 36, 57, 71 and follow-up visit on Day 99
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO7049665 in people with Ulcerative Colitis, run by Hoffmann-La Roche at 6 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Hungary, United States, Georgia, Moldova, Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From baseline up to safety follow-up visit on Day 99). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2024.