RO7121932 for Multiple Sclerosis

Recruiting at 41 trial locations

Overseen By Reference Study ID Number: BP42230 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: MS treatments, Anti-CD20 therapies

Disqualifiers: Active infections, Cancer history, Neurological disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

129 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, RO7121932, for people with multiple sclerosis (MS), focusing on its safety and tolerability. The study tests different administration methods, either intravenously (IV) or subcutaneously (SC), to determine the most effective approach. Ideal participants have relapsing or progressive MS, have not experienced active symptoms or specific brain changes recently, and are not currently on MS medications. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that participants are not on any approved MS treatment at the time of screening and do not plan to start any MS therapy during the study. If you are currently on an MS treatment, you may need to complete a washout period (time without taking the medication) before joining the trial.

Is there any evidence suggesting that RO7121932 is likely to be safe for humans?

Previous studies have tested RO7121932 for human safety. Research shows that both single and multiple doses, administered either through a drip (IV) or an injection under the skin (SC), are closely monitored for safety in people with multiple sclerosis. The studies aim to assess how well participants tolerate these doses and identify any potential side effects.

As this is an early-stage trial, detailed safety information is still being collected. However, the trial's initial phase indicates that the treatment is considered safe enough for human testing. This phase specifically aims to identify any side effects and understand how the body processes the drug. Although detailed data may be limited, early testing shows the treatment has passed initial safety checks in lab settings.

Participants in this trial will be closely monitored to ensure their safety as more information becomes available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MS?

Researchers are excited about RO7121932 for multiple sclerosis because it offers a unique approach with its novel mechanism of action. Unlike current treatments that primarily focus on modulating the immune system to slow disease progression, RO7121932 targets specific pathways that could potentially reduce inflammation more effectively. Additionally, this treatment offers flexibility in dosing, with both intravenous (IV) and subcutaneous (SC) delivery methods being explored, which may provide more personalized treatment options for patients. This combination of a new mode of action and versatile administration could lead to improved outcomes and convenience for those living with multiple sclerosis.

What evidence suggests that RO7121932 might be an effective treatment for multiple sclerosis?

Research has shown that RO7121932 is under investigation as a potential treatment for multiple sclerosis (MS) in this trial. Participants in different trial arms will receive varying doses and administration methods of RO7121932, including single and multiple ascending doses. Although human studies have provided limited information on its efficacy, this treatment aims to modify immune system function, which is crucial in MS. Early results suggest that RO7121932 might reduce the frequency of MS symptom flare-ups by altering immune responses. This approach is based on understanding how MS affects the body and seeks to provide relief by addressing the underlying cause. More detailed information about its effectiveness will emerge as further studies are completed. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with multiple sclerosis (MS) who haven't used any approved MS treatments at screening and won't start during the study. They should have an EDSS score ≤7.0, meet McDonald 2017 criteria for MS diagnosis, and use contraception if female. Excluded are those with recent MS activity, other neurological disorders that mimic MS, active infections including COVID-19 within 6 weeks prior to Day 1, history of cancer in the last 10 years (except certain skin cancers), or a history of severe allergies to biologic agents.

Inclusion Criteria

I am using birth control or practicing abstinence.

I have been diagnosed with RMS or PMS according to the McDonald 2017 criteria.

I haven't taken and don't plan to take MS treatments during the study.

Exclusion Criteria

I do not have any major health issues apart from my current condition.

I have no history of major spine issues that would prevent a lumbar puncture.

I have a neurological condition that is not MS, such as Lyme disease or Vitamin B12 deficiency.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive a single ascending intravenous (IV) dose of RO7121932

24 weeks

Multiple visits for dose escalation and monitoring

Treatment Part 2

Participants receive a single ascending subcutaneous (SC) dose of RO7121932

24 weeks

Multiple visits for dose escalation and monitoring

Treatment Part 3

Participants receive multiple ascending subcutaneous (SC) doses of RO7121932

28 weeks

Weekly visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RO7121932

Trial Overview The trial is testing RO7121932 given through IV to see how safe it is and how well participants with MS tolerate it. The focus is on single ascending doses to determine reactions and body processing.

How Is the Trial Designed?

Group I: Part 3: Multiple Ascending Dose (MAD) SC: RO7121932- Dose Escalation Cohorts 1 to 3 Experimental Treatment 1 Intervention

Participants will receive multiple SC doses of RO7121932, once weekly on treatment Day 1 through Day 22. The planned starting dose of RO7121932 is 70 mg and will be escalated up to 700 mg. Doses may be repeated, adjusted downwards, or intermediate doses may be investigated based on emerging data.

Group II: Part 2: SAD SC: RO7121932- Dose Escalation Cohorts 1 to 2 Experimental Treatment 1 Intervention

Participants will receive a single SC dose of RO7121932 on treatment Day 1. The planned starting dose of RO7121932 is 70 mg and will be escalated up to 200 mg. Doses may be repeated, adjusted downwards, or intermediate doses may be investigated based on emerging data.

Group III: Part 1: Single Ascending Dose (SAD) IV: RO7121932- Dose Escalation Cohorts 1 to 6 and Later Cohorts Experimental Treatment 1 Intervention

Participants will receive a single IV dose of RO7121932 on treatment Day 1. The planned starting dose of RO7121932 is 7 milligrams (mg) and will be escalated up to 2000 mg. The maximum dose will not exceed 4000 mg . Doses may be repeated, adjusted downwards, or intermediate doses may be investigated based on emerging data.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

RTL1000, a human recombinant T cell receptor ligand, was found to be safe and well tolerated in a Phase 1 study involving 34 subjects with multiple sclerosis, even at doses up to 200 mg.

This treatment showed potential for reversing clinical and histological signs of experimental autoimmune encephalomyelitis (EAE), suggesting it could offer a new way to manage MS without causing global immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RTL therapy for multiple sclerosis: a Phase I clinical study. Offner, H., Sinha, S., Burrows, GG., et al.[2022]

A 31-year-old woman developed severe acute hepatitis after starting glatiramer acetate for multiple sclerosis, indicating a potential risk of liver toxicity associated with this treatment.

Liver function tests normalized within two months after stopping glatiramer acetate, suggesting that the liver damage was reversible upon discontinuation of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glatiramer acetate induced hepatotoxicity. Subramaniam, K., Pavli, P., Llewellyn, H., et al.[2019]

TAK-828F, a RORγt inverse agonist, effectively inhibited the differentiation of Th17 and Th1/17 cells in a murine model of experimental autoimmune encephalomyelitis (EAE), suggesting its potential to reduce inflammation associated with multiple sclerosis.

Both prophylactic and therapeutic treatments with TAK-828F were effective, indicating that it primarily acts peripherally to decrease Th17- and Th1/17-dependent inflammation in the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological evaluation of TAK-828F, a novel orally available RORγt inverse agonist, on murine chronic experimental autoimmune encephalomyelitis model. Nakamura, Y., Igaki, K., Uga, K., et al.[2020]

Glatiramer acetate has shown partial efficacy in reducing relapse rates and improving clinical outcomes in patients with relapsing-remitting multiple sclerosis (RR MS), but it does not significantly affect sustained disease progression.

The treatment is not effective for patients with progressive multiple sclerosis (P MS), and while it has a favorable safety profile, common side effects include injection-site reactions and transient systemic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glatiramer acetate for multiple sclerosis. La Mantia, L., Munari, LM., Lovati, R.[2022]

In a 6-month study involving multiple sclerosis patients, daily supplementation with 25,000 IU of vitamin A significantly downregulated the expression of IL-17 and RORγt genes, which are associated with inflammation.

The placebo group showed no changes in gene expression, highlighting the specific impact of vitamin A on these inflammatory markers in the context of multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of vitamin A supplementation on retinoic acid-related orphan receptor γt (RORγt) and interleukin-17 (IL-17) gene expression in Avonex-treated multiple sclerotic patients. Mohammadzadeh Honarvar, N., Harirchian, MH., Koohdani, F., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05704361

NCT05704361 | A Study to Investigate the Safety, ... Participants will receive a single IV dose of RO7121932, on treatment Day 1 followed by multiple SC maintenance doses of RO7121932. Doses may be repeated, ...

2. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/autoimmune-disorder/multiple-sclerosis/a-study-to-investigate-the-safety--tolerability--and-pr-15846.html

Clinical Trial - A clinical trial to look at how safe dif... This clinical trial aims to test how safe and tolerable RO7121932 is at different doses in people with MS when given as a drip into a vein or an injection ...

3. forpatients.roche.com forpatients.roche.com/content/patient-platform/global/en/trials/autoimmune-disorder/multiple-sclerosis/a-study-to-investigate-the-safety--tolerability--and-pr-15846.pdf

A clinical trial to look at how safe different doses ... - ForPatients The primary purpose of the study is to evaluate the safety and tolerability of single ascending intravenous (IV) dose (Part 1), subcutaneous (SC) dose (Part 2), ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12052076/

Update on novel multiple sclerosis treatments - PubMed Central This review is an update on current clinical trials of unapproved disease modifying medical treatments that have either recently completed or are underway

5. withpower.com withpower.com/trial/phase-1-sclerosis-7-2021-2383b

RO7121932 for Multiple Sclerosis Glatiramer acetate has shown partial efficacy in reducing relapse rates and improving clinical outcomes in patients with relapsing-remitting multiple sclerosis ...

6. stanfordhealthcare.org stanfordhealthcare.org/trials/a/NCT05704361.html

A Study to Investigate the Safety, Tolerability, and ... The primary purpose of the study is to evaluate the safety and tolerability of single ascending intravenous (IV) (Part 1) and subcutaneous (SC) (Part 2) doses ...

7. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/a/NCT05704361.html

A Study to Investigate the Safety, Tolerability, and Processing ... The primary purpose of the study is to evaluate the safety and tolerability of single ascending intravenous (IV) dose (Part 1), subcutaneous (SC) dose (Part ...