IMU-838 for Progressive Multiple Sclerosis

(CALLIPER Trial)

Recruiting at 94 trial locations

Overseen By Andreas Muehler, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Immunic AG

Must not be taking: MS treatments

Disqualifiers: Neuromyelitis optica, Myelitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new medication called IMU-838 to help adults with Progressive Multiple Sclerosis. The medication aims to reduce inflammation and slow down the worsening of the disease. The study will check if the medication is safe and effective over a long period.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that previous or current use of MS treatments may be a factor. It's best to discuss your specific medications with the trial coordinators.

What is known about the safety of IMU-838 (Vidofludimus calcium) in humans?

IMU-838 (Vidofludimus calcium) has been studied for safety in healthy male subjects and patients with conditions like rheumatoid arthritis and Crohn's disease. Some studies reported hematuria (blood in urine) at higher doses, which seemed to be related to the amount taken. ^{1 2 3 4 5}

What makes the drug IMU-838 unique for treating progressive multiple sclerosis?

IMU-838 (Vidofludimus calcium) is unique because it works by selectively inhibiting an enzyme called DHODH, which is involved in the metabolism of cells, particularly affecting immune cells that contribute to inflammation in multiple sclerosis. This mechanism is different from many other treatments that primarily focus on modulating the immune system more broadly. ^{6 7 8 9 10}

What data supports the effectiveness of the drug IMU-838 for Progressive Multiple Sclerosis?

Research on teriflunomide, a similar drug, shows it can help manage multiple sclerosis by reducing relapses and improving quality of life. This suggests that IMU-838, which is related, might also be effective for progressive multiple sclerosis. ^{2 11 12 13 14}

Who Is on the Research Team?

Robert J. Fox, MD

Principal Investigator

Mellen Center for MS, Neurological Institute, Cleveland Clinic, Ohio

Are You a Good Fit for This Trial?

Adults aged 18-65 with Progressive Multiple Sclerosis (SPMS or PPMS) who haven't had a relapse in the last 24 months. They must have an EDSS score of 3.0 to 6.5, show disability progression not related to relapses, and be able to follow the study protocol. Excluded are those with other possible causes for symptoms, previous MS treatments within certain timeframes, recent SARS-CoV-2 infection without negative tests, positive tests for TB or hepatitis B/C/HIV, use of investigational products recently, or signs of NMO/MOG-associated encephalomyelitis.

Inclusion Criteria

I haven't had a relapse in 2 years and my diagnosis follows specific criteria.

Your EDSS score at screening is between 3.0 and 6.5.

My condition has not worsened in the last 2 years.

Exclusion Criteria

My symptoms are not caused by conditions other than MS.

I haven't used any experimental drugs recently.

I tested positive for COVID-19 within the last 14 days or have recently recovered with negative tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Main Treatment

Participants receive either IMU-838 or placebo daily to evaluate efficacy, safety, and tolerability

120 weeks

Open Label Extension

Participants may opt into continuation of treatment with IMU-838 long-term

Up to 8 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IMU-838

Trial Overview The CALLIPER trial is testing IMU-838's effectiveness and safety against a placebo in managing Progressive Multiple Sclerosis. Participants will be randomly assigned to either receive IMU-838 or a matching placebo in this double-blind study where neither they nor the researchers know who gets which treatment.

How Is the Trial Designed?

Group I: IMU-838 Experimental Treatment 1 Intervention

IMU-838 as tablet; Administration: Oral - daily

Group II: Placebo Placebo Group 1 Intervention

Matching placebo as tablet; Administration: Oral - daily

Who Is Running the Clinical Trial?

Immunic AG

Lead Sponsor

Trials

8

Recruited

3,300+

Published Research Related to This Trial

In a 6-month phase II trial involving patients with secondary progressive multiple sclerosis, the novel immunosuppressive drug β-D-Mannuronic acid (M2000) showed a significant reduction in disability progression compared to conventional treatments, with a notable decrease in the Expanded Disability Status Scale (EDSS) score (p < 0.009).

M2000 demonstrated better performance in MRI-related measurements compared to conventional drugs, and importantly, no short-term side effects were observed, indicating its potential safety and efficacy as a treatment option for MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled, randomized phase II clinical trial for efficacy and safety evaluation of mannuronic acid in secondary progressive form of multiple sclerosis. Najafi, S., Moghadam, NB., Saadat, P., et al.[2022]

Teriflunomide, an oral treatment for relapsing-remitting multiple sclerosis, has shown consistent efficacy in clinical trials, with safety data pooled from over 3044 patients and a treatment duration exceeding 12 years.

The safety profile of teriflunomide is manageable, with common side effects including ALT increase, headache, diarrhea, hair thinning, and nausea, mostly mild-to-moderate in intensity, and no new safety concerns identified in long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions. Comi, G., Freedman, MS., Kappos, L., et al.[2022]

Vidofludimus (IMU-838) demonstrated good safety and tolerability in healthy male subjects across a wide dose range (10-50 mg) during two phase 1 studies, indicating it may be a safe option for treating conditions like rheumatoid arthritis and Crohn's disease.

The pharmacokinetics of IMU-838 were dose-proportional, with steady-state concentrations reached within 6-8 days, supporting its use as a once-daily oral medication without food affecting its absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability and Pharmacokinetics of Vidofludimus calcium (IMU-838) After Single and Multiple Ascending Oral Doses in Healthy Male Subjects. Muehler, A., Kohlhof, H., Groeppel, M., et al.[2021]

In a 24-week phase 2 trial involving patients with relapsing-remitting multiple sclerosis, vidofludimus calcium significantly reduced the number of new MRI brain lesions compared to placebo, indicating its efficacy in managing the disease.

The treatment was well tolerated, with no significant increase in serious adverse events or common side effects, suggesting a favorable safety profile for vidofludimus calcium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis. Fox, RJ., Wiendl, H., Wolf, C., et al.[2022]

The EDMUS database is a user-friendly system designed to collect and analyze data related to Multiple Sclerosis (MS), facilitating ongoing international multicenter trials.

Current studies using the EDMUS system include evaluations of treatment effects, such as the impact of pregnancy on MS and the effectiveness of early treatments with azathioprine and interferon-beta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EDMUS--a new European databank for multiple sclerosis. A brief introduction of ongoing and planned multicenter studies within the scope of the "European Concentrated Action for Multiple Sclerosis"]. Flachenecker, P., Hartung, HP.[2013]

The abstract lists a wide range of medical interventions, including various drugs and therapies, indicating a focus on diverse treatment options for different conditions.

However, the abstract does not provide specific findings related to safety, efficacy, or mechanisms of action for any of the listed interventions, making it difficult to extract key takeaways regarding their clinical impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. Bayes, M., Rabasseda, X., Prous, JR.[2007]

In a patient with metastatic castration-resistant prostate cancer (mCRPC), four cycles of radioligand therapy (RLT) using 177Lu-PSMA I&T resulted in over 97% destruction of metastatic tumors, indicating high efficacy of this treatment.

The study highlights the need for individualized dosimetry to account for variations in tumor response and suggests that measuring 177Lu-PSMA activity concentrations could improve routine dosimetry practices, while also noting that the first cycle of RLT has the most significant impact on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer-A Model Based on Clinical Example. Kelk, E., Ruuge, P., Rohtla, K., et al.[2021]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of [177Lu]Lu-PSMA-617 to standard care significantly delayed the time to first symptomatic skeletal event, with a median of 11.5 months compared to 6.8 months for standard care alone.

Patients receiving [177Lu]Lu-PSMA-617 also reported improved health-related quality of life and less pain, although there were some serious adverse events, including hematological issues, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Fizazi, K., Herrmann, K., Krause, BJ., et al.[2023]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Teriflunomide for the treatment of relapsing multiple sclerosis: a review of clinical data. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Multiple sclerosis relapses are associated with increased fatigue and reduced health-related quality of life - A post hoc analysis of the TEMSO and TOWER studies. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A controlled, randomized phase II clinical trial for efficacy and safety evaluation of mannuronic acid in secondary progressive form of multiple sclerosis. [2022]

4. Egypt pubmed.ncbi.nlm.nih.gov

Teriflunomide Safety and Efficacy in Advanced Progressive Multiple Sclerosis. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Safety, Tolerability and Pharmacokinetics of Vidofludimus calcium (IMU-838) After Single and Multiple Ascending Oral Doses in Healthy Male Subjects. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

[EDMUS--a new European databank for multiple sclerosis. A brief introduction of ongoing and planned multicenter studies within the scope of the "European Concentrated Action for Multiple Sclerosis"]. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Immunomodulatory agents for the treatment of relapsing multiple sclerosis: a systematic review. [2019]

10. Spain pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. [2007]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer-A Model Based on Clinical Example. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Preparation of 177Lu-PSMA-617 in Hospital Radiopharmacy: Convenient Formulation of a Clinical Dose Using a Single-Vial Freeze-Dried PSMA-617 Kit Developed In-House. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. [2023]