A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of RO7268489 as Add-on Therapy to Ocrelizumab, in Participants With Progressive Forms of Multiple Sclerosis (MS) (Mintaka)

A Multi-center, Double-blind, Placebo-controlled, Phase II Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of RO7268489, a Monoacylglycerol Lipase Inhibitor, as Add-on Therapy to Ocrelizumab, in Participants With Progressive Forms of Multiple Sclerosis

The main purpose of this study is to assess the efficacy of RO7268489 in adults with progressive multiple sclerosis (PMS) receiving ocrelizumab. After the end of the double-blind period, an open-label (OL) extension may allow eligible participants to receive open-label RO7268489.

Study Overview

• Status: Recruiting
• Conditions: Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: RO7268489; Drug: Ocrelizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BP46016 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • Southern Neurology
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health
• France
  • Bron, France, 69500
    • Recruiting
    • Hopital Neurologique Pierre Wertheimer
  • Paris, France, 75013
    • Recruiting
    • Groupe Hospitalier Pitie-Salpetriere
  • Rennes, France, 35033
    • Recruiting
    • CHU Rennes - Hôpital Pontchaillou
  • Gard
    • Nîmes, Gard, France, 30029
      • Recruiting
      • Hopital Caremeau
  • Gironde
    • Bordeaux, Gironde, France, 33800
      • Recruiting
      • Groupe Hospitalier Pellegrin
  • Haute Garonne
    • Toulouse, Haute Garonne, France, 31059
      • Recruiting
      • Hopital Purpan
  • Herault
    • Montpellier, Herault, France, 34295
      • Recruiting
      • Hôpital Gui de Chauliac
  • Loire Atlantique
    • Saint-Herblain, Loire Atlantique, France, 44800
      • Recruiting
      • CHU Nantes - Hopital Nord Laënnec
  • Meurthe Et Moselle
    • Nancy, Meurthe Et Moselle, France, 54035
      • Recruiting
      • CHU Nancy Hôpital Central
  • Puy De Dome
    • Clermont-Ferrand, Puy De Dome, France, 63003
      • Recruiting
      • CHU Hôpital Gabriel Montpied
• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité Universitaetsmedizin Berlin - Campus Ch
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Recruiting
      • Universitaetsklinikum Tuebingen
    • Ulm, Baden-Wurttemberg, Germany, 89073
      • Recruiting
      • Studienzentrum Neuropoint GmbH,
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Universitaetsklinikum Erlangen
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • Klinikum rechts der Isar der TU Muenchen
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Recruiting
      • Universitaetsklinikum Carl Gustav Carus TU Dresden
• Hungary
  • Budapest, Hungary, 1033
    • Recruiting
    • ClinExpert Kft.
  • Budapest, Hungary, 1045
    • Recruiting
    • S-Medicon Egeszsegugyi Szolgaltato Kft.
  • Baranya
    • Pécs, Baranya, Hungary, 7623
      • Recruiting
      • Pécsi Tudományegyetem Klinikai Központ
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • Recruiting
      • Azienda Ospedaliera Universitaria Federico II
    • Naples, Campania, Italy, 80138
      • Recruiting
      • Azienda Ospedaliera Universitaria- Universit degli Studi della Campania Luigi Vanvitelli
    • Salerno, Campania, Italy, 84131
      • Recruiting
      • Az. Osp. OO.RR. S. Giovanni di Dio e Ruggi D' Aragona
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Recruiting
      • Fondazione IRCCS Istituto Neurologico Carlo Besta
    • Milan, Lombardy, Italy, 20162
      • Recruiting
      • Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
• New Zealand
  • Auckland, New Zealand, 1010
    • Recruiting
    • Optimal Clinical Trials - Central
  • South Island
    • Christchurch Central City, South Island, New Zealand, 8011
      • Recruiting
      • Optimal Clinical Trials - Christchurch
• Poland
  • ?ory, Poland, 44-240
    • Recruiting
    • ProNeuro Centrum Medyczne
  • ?ód?, Poland, 90-368
    • Recruiting
    • SOMED - Lodzkie Centrum Osteoporozy
  • Katowice, Poland, 40-571
    • Recruiting
    • M.A. LEK A.M.Maciejowscy SC.
  • Kielce, Poland, 25-726
    • Recruiting
    • Resmedica NZOZ Kielce
  • Krakow, Poland, 31-503
    • Recruiting
    • Samodzielny Publiczny Zakad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
  • Krakow, Poland, 31-826
    • Recruiting
    • Szpital Specjalistyczny im. L. Rydygiera w Krakowie
  • Lublin, Poland, 20-410
    • Recruiting
    • Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
  • Lublin, Poland, 20-601
    • Recruiting
    • Zanamed Medical Clinic sp z o o
  • Rzeszów, Poland, 35-055
    • Recruiting
    • Centrum Medyczne Medyk
  • Warsaw, Poland, 01-684
    • Recruiting
    • Centrum Medyczne Neuroprotect
  • Wroc?aw, Poland, 54-239
    • Recruiting
    • Penta Hospitals Przychodnie, Wroclaw Wejherowska
  • Zabrze, Poland, 41-800
    • Recruiting
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanislawa SzyszkoSUM w Katowicach
  • Podkarpackie Voivodeship
    • Rzeszw, Podkarpackie Voivodeship, Poland, 35-323
      • Recruiting
      • Nmedis sp. z o.o.
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-749
      • Recruiting
      • NEURO-CARE Sp. z o.o. Sp. Komandytowa
    • Katowice, Silesian Voivodeship, Poland, 40-081
      • Recruiting
      • Centrum Medyczne Pratia Katowice I
• Portugal
  • Braga, Portugal, 4710-243
    • Recruiting
    • Hospital de Braga
  • Lisbon, Portugal, 1169-050
    • Recruiting
    • ULS São José - Hospital de Sto António dos Capuchos;CRI Esclerose Múltipla
• Spain
  • Albacete, Spain, 02008
    • Recruiting
    • Complejo Hospitalario Universitario de Albacete
  • Barcelona, Spain, 08003
    • Recruiting
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d Hebron
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clínico San Carlos
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28006
    • Recruiting
    • Hospital Universitario De La Princesa
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Regional Universitario de Malaga
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politecnic La Fe
  • Girona
    • Salt, Girona, Spain, 17190
      • Recruiting
      • Hospital Santa Caterina
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Recruiting
      • Hospital Universitario Quironsalud Madrid
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Universitario Virgen de la Arrixaca
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Recruiting
      • Hospital Alvaro Cunqueiro
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06500
    • Recruiting
    • Gazi University Medical Faculty
  • Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • Ankara City Hospital
  • Ankara, Turkey (Türkiye), 06100
    • Recruiting
    • Hacettepe University of Medicine
  • Istanbul, Turkey (Türkiye), 34098
    • Recruiting
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey (Türkiye), 34093
    • Recruiting
    • Istanbul University Istanbul Medical Faculty
  • Istanbul, Turkey (Türkiye), 34785
    • Recruiting
    • Sancaktepe Sehit Prof Dr Ilhan Varank Training and Research Hospital
  • Izmit
    • Kocaeli, Izmit, Turkey (Türkiye), 41380
      • Recruiting
      • Kocaeli University Medical Faculty
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Recruiting
    • University Hospital of Wales
  • Salford, United Kingdom, M6 8HD
    • Recruiting
    • Salford Care Organisation
  • Swansea, United Kingdom, SA6 6NL
    • Recruiting
    • Morriston Hospital
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3HD
      • Recruiting
      • Royal Cornwall Hospital
  • Greater London
    • London, Greater London, United Kingdom, W6 8RF
      • Recruiting
      • Charing Cross Hospital
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom, G51 4TF
      • Recruiting
      • Queen Elizabeth University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• PMS, in accordance with the revised 2017 McDonald criteria
• Expanded disability status scale (EDSS) at screening between 3.0 and 6.0 inclusive

Exclusion Criteria:

• MS relapse during the 6 months preceding the randomization date
• Lack of peripheral venous access
• History of alcohol or other drug abuse, in the opinion of the investigator, within 5 years prior to screening
• Inability to complete an magnetic resonance imaging (MRI)
• Contraindications to ocrelizumab mandatory pre-medications
• Treatment with intravenous immunoglobulin (IV Ig) or plasmapheresis within 12 weeks prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7268489 Dose 1 + Ocrelizumab; Participants will receive RO7268489 along with ocrelizumab as per the pre-defined regimen.	Drug: RO7268489; RO7268489 will be administered per schedule as specified in the arms.; Drug: Ocrelizumab; Ocrelizumab will be administered per schedule as specified in the arms.; Other Names: RO4964913, Ocrevus
Experimental: RO7268489 Dose 2 + Ocrelizumab; Participants will receive RO7268489 along with ocrelizumab as per the pre-defined regimen.	Drug: RO7268489; RO7268489 will be administered per schedule as specified in the arms.; Drug: Ocrelizumab; Ocrelizumab will be administered per schedule as specified in the arms.; Other Names: RO4964913, Ocrevus
Experimental: RO7268489 Dose 3 + Ocrelizumab; Participants will receive RO7268489 along with ocrelizumab as per the pre-defined regimen.	Drug: RO7268489; RO7268489 will be administered per schedule as specified in the arms.; Drug: Ocrelizumab; Ocrelizumab will be administered per schedule as specified in the arms.; Other Names: RO4964913, Ocrevus
Placebo Comparator: Placebo + Ocrelizumab; Participants will receive RO7268489 matching placebo along with ocrelizumab as per the pre-defined regimen.	Drug: Ocrelizumab; Ocrelizumab will be administered per schedule as specified in the arms.; Other Names: RO4964913, Ocrevus; Drug: Placebo; Placebo will be administered per schedule as specified in the arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Randomization to the First Occurrence of Composite Confirmed Disability Progression (cCPD) Confirmed for at Least 12 Weeks (cCDP12)	Time from randomization to the first occurrence of cCDP12 according to at least one of the following 3 criteria: 12-week confirmed disability progression (CDP12); 12-week confirmed increase in Timed 25-Foot Walk Test (T25FWT) or; 12-week confirmed increase in 9-Hole Peg Test (9-HPT) The EDSS is a disability scale is based on a standard neurological examination that ranges in 0.5-point steps from 0 (normal) - 10 (death). T25FWT=time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, the higher score, which indicates deterioration. Lower times indicate better performance and greater mobility. In 9-HPT, participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. The shorter time it takes to complete the task indicates a better outcome.	Up to approximately 110 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Randomization to the First Occurrence of 24-Week Confirmed ≥4-Point Decrease (Worsening) in Symbol Digit Modalities Test (SDMT)	The SDMT is a performance measure of processing speed that is widely used to assess cognitive function in response to treatment. It's brief, easy to administer, and involves a simple substitution task that healthy children and adults can easily perform. Using a reference key, the participant has 90 seconds to pair specific numbers with given geometric figures. The total SDMT score is the total number of correct responses and ranges from 0 to 110, with a higher score indicating a higher level of processing speed. A four-point change from baseline is typically considered clinically meaningful.	Up to approximately 110 weeks
Change From Baseline in Total Brain Volume		Up to approximately 110 weeks
Time to Onset of 24-Week cCDP (cCDP24)		Up to approximately 110 weeks
Time to Onset of 12-Week Confirmed Disability Progression CDP (CDP12)		Up to approximately 110 weeks
Time to Onset of 24-Week CDP (CDP24)		Up to approximately 110 weeks
Time to ≥ 20% Increase in 12-week Confirmed Timed 25-Foot Walk Test (T25FWT)	The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, higher the score, which indicates deterioration and greater impairment. Lower times indicate better performance and greater mobility. Lower the mean change in the score over time, the better performance.	Up to approximately 110 weeks
Time to ≥ 20% Increase in 24-week Confirmed T25FWT	The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, higher the score, which indicates deterioration and greater impairment. Lower times indicate better performance and greater mobility. Lower the mean change in the score over time, the better performance.	Up to approximately 110 weeks
Time to ≥ 20% Increase in 12-week Confirmed 9-Hole Peg Test (9-HPT)	Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. More time = higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance.	Up to approximately 110 weeks
Time to ≥ 20% Increase in 24-week Confirmed 9-HPT	Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. More time = higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance.	Up to approximately 110 weeks
Plasma 2-arachidonoylglycerol (2-AG) Levels		Up to approximately 110 weeks
Change From Baseline in Plasma 2-AG Levels		Up to approximately 110 weeks
Number of Participants With Adverse events (AEs)		Up to 5 years
Number of Participants With Treatment Discontinuations due to AEs		Up to 5 years
Proportion of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)	C-SSRS is an assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher indicate suicidal ideation or behavior.	Up to 5 years
Plasma Concentrations of RO7268489 and Its Metabolite(s)		Up to 5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2030

Study Registration Dates

• First Submitted: December 5, 2025
• First Submitted That Met QC Criteria: December 5, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; ocrelizumab
• Other Study ID Numbers: BP46016; 2025-521636-10-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No