Combination Therapies for Multiple Sclerosis

Recruiting in Palo Alto (17 mi)

Overseen by Bibiana Bielekova, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: MS drugs

Must not be taking: Immunosuppressants, Immunomodulators

Disqualifiers: Cerebrovascular disease, Cardiomyopathy, Clotting disorder, Neurodegenerative disorder, Substance abuse, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests four different drugs, alone or in combination, on adults with progressive multiple sclerosis who are not responding well to current treatments. The goal is to see if these drugs can reduce harmful inflammation and immune activity in the brain and spinal fluid.

Will I have to stop taking my current medications?

The trial requires that participants keep their current MS medication stable during the study. If you need to change your medication, the study drugs will be stopped to establish a new baseline before continuing.

What makes the drug combination of Clemastine Fumarate, Dantrolene, Pioglitazone, and Pirfenidone unique for treating Multiple Sclerosis?

This drug combination is unique because it combines medications typically used for other conditions, like allergies (Clemastine), muscle spasms (Dantrolene), diabetes (Pioglitazone), and lung fibrosis (Pirfenidone), to potentially offer a novel approach to treating Multiple Sclerosis, which currently lacks a standard treatment. ^{1 2 3 4 5}

Research Team

Bibiana Bielekova, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

Adults over 18 with progressive MS, able to walk a few steps, and currently in protocol 09-I-0032 can join. They must have shown MS progression and agree to birth control if applicable. Participants can continue their FDA-approved MS drugs but may need to stop if they change treatments.

Inclusion Criteria

My condition has worsened by at least 0.5 points/year over 1.5 years.

My disability level is moderate to severe but I can still perform some daily activities.

I am willing to keep my current FDA-approved MS treatment stable during the study.

Exclusion Criteria

I am not allergic to Dantrolene, have no liver problems, and no history of liver issues caused by drugs or alcohol.

I am not allergic to Pirfenidone, do not have liver disease, my liver tests are normal, and I do not smoke.

Abnormal screening/baseline blood tests exceeding any of the limits defined below: Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values, Total white blood cell count less than 3,000/mm^3, Platelet count less than 85,000/mm^3, Serum creatinine level greater than 2.0 mg/dl and eGFR (glomerular filtration rate) less than 60, Serological evidence of HIV, HTLV-1 or active hepatitis A, B or C, Positive pregnancy test

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy

Participants receive one of the study drugs for up to 18 months, with regular assessments of CSF biomarkers to determine drug efficacy.

18 months

2 visits per year (in-person)

Combination Therapy

Participants may start a second drug, continuing for an additional 18 months if the first drug is effective.

18 months

2 visits per year (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a call 3 months after stopping the drugs.

3 months

Treatment Details

Interventions

• Clemastine Fumarate (Other)
• Dantrolene (Other)
• Pioglitazone (Other)
• Pirfenidone (Other)

Trial Overview The trial tests whether Dantrolene, Pirfenidone, Pioglitazone, or clemastine fumarate alone or combined affect MS biomarkers in the brain/CSF. It aims to predict drug response based on these biomarker changes during up to an 18-month treatment period.

Participant Groups

Group I: Monotherapy Experimental Treatment 4 Interventions

Any of the study Interventions

Group II: Combination Therapy Experimental Treatment 4 Interventions

Any two-drug combination of study interventions

Clemastine Fumarate is already approved in Canada for the following indications:

Approved in Canada as Clemastine for:

• Allergic rhinitis
• Urticaria
• Pruritus

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

Findings from Research

The combination therapy of S-1 and paclitaxel (PTX) showed promising efficacy in patients with previously treated non-small cell lung cancer (NSCLC), achieving a response rate of 27.5% and a disease control rate of 75% among 40 enrolled patients.

The treatment was associated with manageable safety profiles, with only mild to moderate toxicities reported, such as grade 3/4 anemia in 12% of patients, and no treatment-related deaths, indicating that this combination therapy is a feasible option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of S-1 and Paclitaxel Combination Therapy in Patients with Previously Treated Non-Small Cell Lung Cancer. Chihara, Y., Yoshimura, A., Date, K., et al.[2020]

A new regimen combining doxorubicin and paclitaxel has been developed that is both well-tolerated and highly effective, utilizing bolus administration of doxorubicin and a 3-hour infusion of paclitaxel, overcoming previous schedule-dependent toxicity issues.

Paclitaxel has shown promising results when combined with fluorouracil and folinic acid in patients with extensive prior chemotherapy, and adding mitoxantrone to this combination appears to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-based combination chemotherapy for breast cancer. Hortobagyi, GN.[2015]

In a study of 201 patients with hormone-refractory prostate cancer, the combination of vinblastine and estramustine (EM-V) showed a significantly longer time to disease progression compared to vinblastine alone, with median times of 3.7 months versus 2.2 months, respectively.

While overall survival was not significantly different between the two treatments, EM-V resulted in a higher percentage of patients achieving a significant decline in prostate-specific antigen (PSA) levels (25.2% vs. 3.2%), indicating better efficacy in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: A Hoosier Oncology Group and Fox Chase Network phase III trial. Hudes, G., Einhorn, L., Ross, E., et al.[2017]

Combining paclitaxel with doxorubicin has shown impressive remission rates for metastatic breast cancer, with overall rates exceeding 90% and nearly 50% achieving complete remission, especially when administered in a specific sequence.

While other combinations of paclitaxel with drugs like cisplatin and vinorelbine have shown variable results, the doxorubicin/paclitaxel combination remains the most effective and tolerable treatment option currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. Hortobagyi, GN., Ibrahim, N.[2018]

Paclitaxel has shown single-agent activity in breast cancer, leading to ongoing trials exploring its effectiveness in various combinations with other drugs like doxorubicin, cisplatin, and cyclophosphamide.

Despite numerous studies, no optimal combination regimen for paclitaxel has been established yet, highlighting the need for well-designed trials to safely explore these combinations due to the unpredictable nature of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel combination therapy in the treatment of metastatic breast cancer. Holmes, FA.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II Study of S-1 and Paclitaxel Combination Therapy in Patients with Previously Treated Non-Small Cell Lung Cancer. [2020]

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

Paclitaxel-based combination chemotherapy for breast cancer. [2015]

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

Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: A Hoosier Oncology Group and Fox Chase Network phase III trial. [2017]

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

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. [2018]

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

Paclitaxel combination therapy in the treatment of metastatic breast cancer. [2015]