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NCT03943550

Double-Blinded, Placebo-Controlled Phase 1b Study for Safety, PK, Efficacy, PD of RO7049665 in Participants With Ulcerative Colitis (UC)

Terminated Phase 1 Results posted Last updated 15 February 2024
What this trial tests

Phase 1 trial testing RO7049665 in Ulcerative Colitis in 45 participants. Terminated before completion.

Timeline
13 May 2019
Primary endpoint
22 July 2021
22 July 2021

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingdouble
Primary purposetreatment
Enrollment45
Start date13 May 2019
Primary completion22 July 2021
Estimated completion22 July 2021
Sites6 locations across Georgia, Ukraine, Moldova, Hungary, United States

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 18 to 70, any sex, with Ulcerative Colitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · 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, requi

Number of participants with at least 1 AE
GroupValue95% CI
Placebo4
RO7049665 3.5 mg6
RO7049665 7.5 mg24
Number of participants with at least one SAE
GroupValue95% CI
Placebo0
RO7049665 3.5 mg0
RO7049665 7.5 mg1
Time to Maximum Concentration (Tmax) of RO7049665 Secondary · Day 1 to Day 15 (predose) and Day 43 (post-dose)
Day 1-Day 15: Dose 1
GroupValue95% CI
RO7049665 3.5 mg12.006.00 – 24.00
RO7049665 7.5 mg24.006.00 – 72.08
Day 43: Dose 4
GroupValue95% CI
RO7049665 3.5 mg18.0612.00 – 72.57
RO7049665 7.5 mg24.0012.00 – 73.17
Maximum Serum Concentration Observed (Cmax) of RO7049665 Secondary · Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
Day 1: Dose 1
GroupValue95% CI
RO7049665 3.5 mg22.58.59 – 63.7
RO7049665 7.5mg47.613.9 – 250
Day 43: Dose 4
GroupValue95% CI
RO7049665 3.5 mg38.721.8 – 65.4
RO7049665 7.5mg46.520.2 – 109
Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665 Secondary · Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
Day 1: Dose 1
GroupValue95% CI
RO7049665 3.5 mg20301020 – 3550
RO7049665 7.5 mg45201780 – 15100
Day 43: Dose 4
GroupValue95% CI
RO7049665 3.5 mg35201830 – 5740
RO7049665 7.5 mg41102200 – 8240
Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) Secondary · Baseline, Days 29 and 57

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, ulcera

Baseline
GroupValue95% CI
Placebo2.56± 0.53
RO7049665 3.5 mg2.44± 0.53
RO7049665 7.5 mg2.59± 0.50
Change from Baseline at Day 29
GroupValue95% CI
Placebo-0.22± 0.83
RO7049665 3.5 mg-0.22± 0.83
RO7049665 7.5 mg-0.54± 0.98
Change from Baseline at Day 57
GroupValue95% CI
Placebo-0.11± 0.93
RO7049665 3.5 mg0.00± 0.53
RO7049665 7.5 mg-0.42± 0.72
Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Secondary · Baseline, Days 29 and 57

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.

Baseline
GroupValue95% CI
Placebo4.33± 1.12
RO7049665 3.5 mg4.00± 1.73
RO7049665 7.5 mg3.85± 0.86
Change from Baseline at Day 29
GroupValue95% CI
Placebo-0.67± 1.32
RO7049665 3.5 mg-0.22± 1.79
RO7049665 7.5 mg-0.71± 1.52
Change from Baseline at Day 57
GroupValue95% CI
Placebo-0.22± 1.56
RO7049665 3.5 mg0.63± 1.85
RO7049665 7.5 mg-0.71± 1.33
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) Secondary · Baseline, Days 29 and 57

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 ep

Baseline
GroupValue95% CI
Placebo4.56± 0.88
RO7049665 3.5 mg3.22± 1.92
RO7049665 7.5 mg3.54± 2.04
Change from Baseline at Day 29
GroupValue95% CI
Placebo-0.33± 1.22
RO7049665 3.5 mg0.78± 2.49
RO7049665 7.5 mg-0.70± 1.11
Change from Baseline at Day 57
GroupValue95% CI
Placebo-0.89± 1.90
RO7049665 3.5 mg0.88± 2.85
RO7049665 7.5 mg-0.54± 1.82
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) Secondary · Baseline, Days 29 and 57

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.

Baseline
GroupValue95% CI
Placebo18.78± 7.19
RO7049665 3.5 mg11.44± 9.30
RO7049665 7.5 mg14.88± 10.90
Change from Baseline at Day 29
GroupValue95% CI
Placebo-3.11± 8.52
RO7049665 3.5 mg3.89± 11.85
RO7049665 7.5 mg-3.17± 7.36
Change from Baseline at Day 57
GroupValue95% CI
Placebo-6.22± 8.91
RO7049665 3.5 mg5.38± 16.83
RO7049665 7.5 mg-1.25± 8.90
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) Secondary · Baseline, Days 29 and 57

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), an

Baseline
GroupValue95% CI
Placebo3.11± 0.78
RO7049665 3.5 mg2.11± 1.45
RO7049665 7.5 mg2.42± 1.68
Change from Baseline at Day 29
GroupValue95% CI
Placebo-0.56± 1.01
RO7049665 3.5 mg0.33± 1.94
RO7049665 7.5 mg-0.57± 1.08
Change from Baseline at Day 57
GroupValue95% CI
Placebo-0.78± 1.48
RO7049665 3.5 mg0.88± 2.42
RO7049665 7.5 mg-0.25± 1.29
Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response Secondary · Baseline, Days 29 and 57

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.

Day 29
GroupValue95% CI
Placebo11.10.28 – 48.25
RO7049665 3.5 mg33.37.49 – 70.07
RO7049665 7.5mg16.74.74 – 37.38
Day 57
GroupValue95% CI
Placebo22.22.81 – 60.01
RO7049665 3.5 mg50.015.7 – 84.3
RO7049665 7.5mg45.825.55 – 67.18
Number of Participants With Anti-Drug Antibodies (ADAs) Secondary · Baseline; Post-dose on Days 8, 22, 57, 71 and 99; Pre-dose on Days 15, 29 and 43

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).

ADA Positive: Treatment-Induced ADA Response
GroupValue95% CI
Placebo0
RO7049665 3.5 mg6
RO7049665 7.5 mg18
ADA Positive: Treatment-Enhanced ADA Response
GroupValue95% CI
Placebo0
RO7049665 3.5 mg0
RO7049665 7.5 mg2
Change From Baseline in White Blood Cells (Tregs, Teffs) Secondary · Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
CD4 Treg: Baseline
GroupValue95% CI
Placebo37.25± 33.34
RO7049665 3.5 mg42.14± 25.07
RO7049665 7.5 mg51.21± 35.09
CD4 Treg: Change from Baseline at Day 2
GroupValue95% CI
Placebo-2.83± 9.33
RO7049665 3.5 mg-24.33± 19.51
RO7049665 7.5 mg-25.65± 14.19
CD4 Treg: Change from Baseline at Day 6
GroupValue95% CI
Placebo12.17± 22.53
RO7049665 3.5 mg61.80± 31.22
RO7049665 7.5 mg87.37± 66.84
CD4 Treg: Change from Baseline at Day 8
GroupValue95% CI
Placebo3.00± 15.32
RO7049665 3.5 mg66.00± 68.26
RO7049665 7.5 mg169.34± 138.21
CD4 Treg: Change from Baseline at Day 10
GroupValue95% CI
Placebo-8.25± 6.76
RO7049665 3.5 mg27.20± 18.99
RO7049665 7.5 mg137.81± 98.51
CD4 Treg: Change from Baseline at Day 15 (Pre-dose)
GroupValue95% CI
Placebo-3.80± 11.57
RO7049665 3.5 mg16.29± 28.42
RO7049665 7.5 mg37.73± 41.74
CD4 Treg: Change from Baseline at Day 22
GroupValue95% CI
Placebo5.17± 5.89
RO7049665 3.5 mg76.00± 70.04
RO7049665 7.5 mg186.45± 130.40
CD4 Treg: Change from Baseline at Day 29 (Pre-dose)
GroupValue95% CI
Placebo-3.75± 6.55
RO7049665 3.5 mg15.57± 18.74
RO7049665 7.5 mg27.66± 29.09

Adverse events — posted to ClinicalTrials.gov

Time frame: From baseline up to safety follow-up visit on Day 99. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 0/9 (0%)
Deaths: 0/9
RO7049665 3.5 mg
Serious: 0/9 (0%)
Deaths: 0/9
RO7049665 7.5 mg
Serious: 1/27 (4%)
Deaths: 0/27

Serious adverse events (1 terms)

ReactionSystemPlaceboRO7049665 3.5 mgRO7049665 7.5 mg
Colitis ulcerativeGastrointestinal disorders
Other adverse events (23 terms — click to expand)

ReactionSystemPlaceboRO7049665 3.5 mgRO7049665 7.5 mg
Injection site reactionGeneral disorders
EosinophiliaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
Colitis ulcerativeGastrointestinal disorders
NauseaGastrointestinal disorders
Injection related reactionInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
HyperkalaemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
HaemorrhoidsGastrointestinal disorders
Oedema peripheralGeneral disorders
GastroenteritisInfections and infestations
Oral herpesInfections and infestations
Urinary tract infectionInfections and infestations
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
HypocalcaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Colitis ulcerative.

Data from ClinicalTrials.gov NCT03943550 adverse events section.

Sponsor's own description

The principal aim of this study is to evaluate the safety and tolerability of RO7049665 in participants with active ulcerative colitis (UC).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases.
    Raeber ME, Sahin D, Karakus U, Boyman O. · · 2023 · cited 139× · PMID 37004361 · DOI 10.1016/j.ebiom.2023.104539
  2. IL-2-based approaches to Treg enhancement.
    Harris F, Berdugo YA, Tree T. · · 2023 · cited 81× · PMID 36399073 · DOI 10.1093/cei/uxac105
  3. "IL-2 immunotherapy for targeting regulatory T cells in autoimmunity".
    Lykhopiy V, Malviya V, Humblet-Baron S, Schlenner SM. · · 2023 · cited 61× · PMID 37741949 · DOI 10.1038/s41435-023-00221-y
  4. A humanized IL-2 mutein expands Tregs and prolongs transplant survival in preclinical models.
    Efe O, Gassen RB, Morena L, Ganchiku Y, et al · · 2024 · cited 29× · PMID 38426492 · DOI 10.1172/jci173107
  5. Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.
    Tomasovic LM, Liu K, VanDyke D, Fabilane CS, et al · · 2024 · cited 17× · PMID 37999893 · DOI 10.1007/s40259-023-00635-0
  6. Targeting γc family cytokines with biologics: current status and future prospects.
    Bick F, Blanchetot C, Lambrecht BN, Schuijs MJ. · · 2025 · cited 5× · PMID 39967341 · DOI 10.1080/19420862.2025.2468312

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