BOTOX® vs. XEOMIN® for Chronic Migraine

Overseen By Keely C Klaumann, BS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Naval Medical Center Camp Lejeune

Must not be taking: Anticoagulants, Prophylactic headache, Chronic pain

Disqualifiers: Pregnancy, Myasthenia gravis, Epilepsy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to find a new way to treat chronic migraines, particularly for military personnel. It will compare two treatments: BOTOX® (OnabotulinumtoxinA), which requires refrigeration, and XEOMIN® (IncobotulinumtoxinA), which does not. The goal is to determine if XEOMIN® can match the effectiveness of BOTOX® without the storage challenges. The trial seeks participants who experience frequent migraines (15 or more headache days a month, each lasting 4 hours or longer) and have not found success with at least two other migraine treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any prophylactic headache medication 4 weeks before the study starts and during the trial. If you are on chronic pain medication for a chronic condition, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found onabotulinumtoxinA (BOTOX) to be safe and well-tolerated for treating chronic migraines. Serious side effects were rare, with only about 1% of patients requiring hospital care due to worsened migraines. Most patients managed the treatment well without needing to stop it.

Research on incobotulinumtoxinA (XEOMIN) shows that side effects from the injections are usually mild and short-lasting. Serious issues like difficulty swallowing, speaking, or breathing can occur, but they are uncommon. XEOMIN is already used for other conditions, which adds confidence in its safety for new uses like chronic migraines.

Both treatments have a strong safety record, providing participants with confidence in their use in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for chronic migraine because they are exploring the potential differences between two botulinum toxin type A products: BOTOX® and XEOMIN®. While both treatments involve injecting a similar active ingredient into specific sites on the head and neck, XEOMIN® is unique because it is a "naked" neurotoxin, meaning it is free from accessory proteins. This could potentially reduce the risk of the body developing immunity against the treatment, possibly leading to longer-lasting effectiveness. Moreover, both treatments offer a targeted approach for migraine prevention, which can be a game-changer for those who experience frequent, debilitating headaches.

What evidence suggests that this trial's treatments could be effective for chronic migraine?

Research has shown that BOTOX®, one of the treatments in this trial, effectively treats chronic migraines. Studies indicate it can reduce headache days by 8 to 9 each month, with about 74% of patients experiencing a 50% or greater reduction. Participants in this trial may also receive XEOMIN®, another treatment option under study. Early findings suggest that XEOMIN® may also be safe and effective for preventing migraines, offering a similar reduction in migraine days and the convenience of not needing refrigeration. Both treatments relax muscles and block pain signals, reducing the frequency and severity of migraines. ^{2 3 5 6 7}

Who Is on the Research Team?

Jacqueline S Buckley, PharmD

Principal Investigator

Naval Medical Center Camp Lejeune

Are You a Good Fit for This Trial?

This trial is for Department of Defense beneficiaries aged 18-89 with chronic migraines, experiencing at least 15 headache days per month. Participants must have tried and not responded to two different migraine medications, be able to give informed consent in English, and attend follow-up visits. Pregnant or breastfeeding individuals, those allergic to botulinum toxin, on certain medications or with specific medical conditions are excluded.

Inclusion Criteria

Department of Defense (DoD) Beneficiary/TriCare Eligible

I experience 15 or more headache days each month, each lasting 4 hours or more.

Able to read, comprehend, and complete the assessment and diary

Exclusion Criteria

I am on long-term pain medication for a chronic condition.

I have a condition that could affect my muscle function.

I am taking blood thinners in pill form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Baseline

Establish baseline using headache days and questionnaires (HIT-6 and MSQ)

4 weeks

1 visit (in-person)

Treatment

Participants receive either onabotulinumtoxinA or incobotulinumtoxinA injections twice, 12 weeks apart

24 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• IncobotulinumtoxinA (XEOMIN®)
• OnabotulinumtoxinA (BOTOX®)

Trial Overview The study compares BOTOX® (onabotulinumtoxinA), an FDA-approved treatment requiring refrigeration, with XEOMIN® (incobotulinumtoxinA), which doesn't need cooling and is effective off-label for migraines. The goal is to find a viable treatment option that's easier to store especially for military personnel in the field.

How Is the Trial Designed?

Group I: IncobotulinumtoxinA (XEOMIN®) Experimental Treatment 1 Intervention

IncobotulinumtoxinA (XEOMIN®) Group: Administration consists of 31 injections (5 incobotulinumtoxinA (XEOMIN®) units per injection, for a total of 155 units) in the head and neck at two time points (12 weeks apart). Injection sites include the forehead, temples, back of the head, upper neck, and the junction of the shoulder and the neck. A very small (e.g., 30-gauge), very sharp needle will be used to perform the injections.

Group II: OnabotulinumtoxinA (BOTOX®) Active Control 1 Intervention

OnabotulinumtoxinA (BOTOX®) Group: Administration consists of 31 injections (5 onabotulinumtoxinA (BOTOX®) units per injection, for a total of 155units) in the head and neck at two time points (12 weeks apart). Injection sites include the forehead, temples, back of the head, upper neck, and the junction of the shoulder and the neck. A very small (e.g., 30-gauge), very sharp needle will be used to perform the injections.

IncobotulinumtoxinA (XEOMIN®) is already approved in United States, European Union for the following indications:

Approved in United States as XEOMIN for:

• Blepharospasm
• Cervical dystonia
• Upper limb spasticity
• Chronic sialorrhea

Approved in European Union as XEOMIN for:

• Blepharospasm
• Cervical dystonia
• Upper limb spasticity
• Chronic sialorrhea

Who Is Running the Clinical Trial?

Naval Medical Center Camp Lejeune

Lead Sponsor

Trials

3

Recruited

170+

Published Research Related to This Trial

In a study of 175 patients with chronic migraine, increasing the dose of onabotulinumtoxinA from 150 units to 200 units significantly reduced the number of headache days and severe headache days, indicating improved efficacy with higher doses.

The higher dose of onabotulinumtoxinA also led to a decrease in the duration of 'wearing off' periods, suggesting that patients experienced more consistent relief from migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA in chronic migraine: is the response dose dependent? Zandieh, A., Cutrer, FM.[2022]

In a 2-year study involving 172 patients, OnabotulinumtoxinA (BOTOX®) at a dosage of 195 U was found to be more effective than 155 U in reducing headache and migraine days, as well as improving overall headache impact scores.

Both dosages had similar safety profiles, with treatment-related side effects being mild to moderate and transient, indicating that higher doses can be used safely in chronic migraine patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A two years open-label prospective study of OnabotulinumtoxinA 195 U in medication overuse headache: a real-world experience. Negro, A., Curto, M., Lionetto, L., et al.[2022]

In a study of 61 patients with refractory chronic migraine, XEOMIN® (Incobotulinumtoxin A) injections led to over 50% reductions in migraine frequency for 73% of participants, demonstrating its efficacy as a prophylactic treatment.

The treatment showed sustained benefits over an average duration of 21 months, with significant reductions in headache days and medication intake, indicating that XEOMIN® can be a reliable option for patients unresponsive to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monocentric Prospective Study into the Sustained Effect of Incobotulinumtoxin A (XEOMIN®) Botulinum Toxin in Chronic Refractory Migraine. Ion, I., Renard, D., Le Floch, A., et al.[2019]

In the COMPEL Study involving 716 adults with chronic migraine, onabotulinumtoxinA treatment every 12 weeks for 108 weeks resulted in a significant reduction in headache days, with an average decrease of 10.7 days by the end of the study (P < 0.0001).

The treatment was found to be generally safe and well-tolerated, with only 18.3% of patients reporting adverse events, the most common being neck pain, and no deaths reported, indicating a favorable risk-benefit profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study. Blumenfeld, AM., Stark, RJ., Freeman, MC., et al.[2018]

In a study of 11 patients with hemiplegic migraine who received onabotulinumtoxinA injections, 9 patients reported a decrease in the frequency and severity of their migraine aura, indicating its potential efficacy beyond headache prevention.

The results suggest that onabotulinumtoxinA may have a beneficial effect on aura symptoms, with some patients experiencing a 'wearing off' effect around week 9 of treatment, highlighting the need for ongoing management and potential adjustments in treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of OnabotulinumtoxinA on Aura Frequency and Severity in Patients With Hemiplegic Migraine: Case Series of 11 Patients. Chen, TY., Garza, I., Dodick, DW., et al.[2019]

In a study of 725 patients treated with OnabotulinumtoxinA for chronic migraine over one year, 79.3% experienced more than a 50% reduction in headache frequency, demonstrating its effectiveness in a real-life setting.

The study found that starting treatment within the first 12 months of chronic migraine diagnosis significantly increased the likelihood of a positive response, suggesting that early intervention may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA in chronic migraine: predictors of response. A prospective multicentre descriptive study. Domínguez, C., Pozo-Rosich, P., Torres-Ferrús, M., et al.[2019]

IncobotulinumtoxinA (Xeomin) has been shown to be effective and well-tolerated for treating neurological conditions like blepharospasm, cervical dystonia, and post-stroke spasticity, based on randomized controlled trials lasting up to 89 weeks.

The safety profile of incobotulinumtoxinA is favorable, with mild to moderate adverse events such as eyelid ptosis and dry eye, and it has demonstrated therapeutic equivalence to another formulation, onabotulinumtoxinA, in treating blepharospasm and cervical dystonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders. Jost, WH., Benecke, R., Hauschke, D., et al.[2018]

In a study of 52 patients with chronic Lyme borreliosis, untreated patients (31 individuals) exhibited significantly higher frequencies of symptoms such as headache, myalgias, and cranial neuritis compared to treated patients (21 individuals), highlighting the importance of early treatment.

The study suggests that early intervention in Lyme borreliosis is crucial, as untreated patients experienced more severe symptoms and complications, including neuropathy, indicating that prompt treatment may help reduce the severity of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical characteristics and perplexities in the treatment of chronic Lyme borreliosis]. Bojić, I., Begović, V.[2015]

A network meta-analysis of 19 studies involving 2532 patients found no significant differences in treatment effectiveness or adverse outcomes among various antibiotics for early cutaneous Lyme borreliosis, indicating that the choice of antibiotic may not impact treatment success.

Treatment failures were rare, with only 4% at 2 months and 2% at 12 months post-treatment, suggesting that antibiotics are generally effective and safe for managing this condition, although the certainty of evidence was low due to study limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Antibiotic Therapy in Early Cutaneous Lyme Borreliosis: A Network Meta-analysis. Torbahn, G., Hofmann, H., Rücker, G., et al.[2019]

The study analyzed cerebrospinal fluid (CSF) samples from 100 patients across four groups, revealing that high concentrations of CXCL13 were significantly associated with proven Lyme neuroborreliosis (LNB), with a cut-off value of >131 pg/mL for the Luminex assay and >259 pg/mL for the ELISA.

The Luminex assay demonstrated high sensitivity (88%) and specificity (94%), making it a reliable diagnostic tool for distinguishing LNB from other neurological disorders, particularly when correlated with CSF lymphocyte/monocyte counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CXCL13 concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other neurological disorders determined by Luminex and ELISA. Markowicz, M., Schötta, AM., Kundi, M., et al.[2019]

In a study of 65 chronic migraine patients treated with onabotulinumtoxinA (Botox®) over three years, there was a significant reduction in the mean number of monthly headache days, from 7.2 to 3.4 days, indicating sustained efficacy of the treatment.

The therapy was found to be safe and well tolerated, with low rates of adverse events and drop-outs, supporting the long-term use of onabotulinumtoxinA for chronic migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained onabotulinumtoxinA therapeutic benefits in patients with chronic migraine over 3 years of treatment. Vikelis, M., Argyriou, AA., Dermitzakis, EV., et al.[2022]

OnabotulinumtoxinA has been approved for preventing chronic migraines, showing effectiveness in two large controlled trials.

Pragmatic studies in real-life settings have provided valuable insights for managing patients with chronic migraines, highlighting its importance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin for chronic migraine: Clinical trials and technical aspects. Tassorelli, C., Sances, G., Avenali, M., et al.[2018]

In a study of nine patients with lymphocytic meningoradiculitis in Sweden, six showed elevated antibody levels against the Lyme spirochete, suggesting a connection to Lyme disease.

The findings indicate that lymphocytic meningoradiculitis may be related to Lyme disease, potentially representing different manifestations of the same infectious agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bannwarth's syndrome (lymphocytic meningoradiculitis) in Sweden. Ryberg, B.[2018]

A 54-year-old male presented with erythema chronicum migrans (ECM) and neurological symptoms, including lymphocytic meningitis and severe pain, indicating a serious late-stage Lyme disease infection.

The case highlights that neurologic complications, known as Bannwarth syndrome, necessitate high-dose intravenous penicillin treatment for effective management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Erythema chronicum migrans with Bannwarth syndrome (Garin-Bujadoux-Bannwarth meningopolyneuritis)]. Kutzner, H., Wolff, HH., Kömpf, D.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6024863/

Monocentric Prospective Study into the Sustained Effect of ... These results suggest that IncobotulinumtoxinA toxin may be an effective and safe prophylactic treatment for a variety of refractory migraines.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07018713

Study Details | NCT07018713 | A Clinical Trial to Evaluate ... The purpose is to measure the change in monthly migraine days with Xeomin injections compared to Placebo injections. Trial details include: Trial duration: 52 ...

3. merztherapeutics.com merztherapeutics.com/us/merz-therapeutics-announces-first-patients-enrolled-in-two-phase-iii-trials-investigating-xeomin-incobotulinumtoxina-for-migraine-prevention/

North America (US) Trials designed to reflect migraine burden and patient experience; Merz Therapeutics continues to build on established neurotoxin expertise.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5367647/

Botulinum toxin in the management of chronic migraine It has been shown that onabotulinumtoxinA is effective in the reduction of headache frequency and severity in patients with CM.

5. clinicaltrial.be clinicaltrial.be/en/details/76727?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

BOTOX® vs. XEOMIN® for Chronic Migraine Changes in chronic migraine frequency and duration are recorded and compared. Primary outcomes. 1. Headache days per month. To compare the ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/125360s078lbl.pdf

XEOMIN (incobotulinumtoxinA) - accessdata.fda.gov WARNING: DISTANT SPREAD OF TOXIN EFFECT. See full prescribing information for complete boxed warning. The effects of XEOMIN and all botulinum toxin products ...

7. botoxchronicmigraine.com botoxchronicmigraine.com/

BOTOX® (onabotulinumtoxinA) - Chronic Migraine Treatment Learn about BOTOX® for adults with Chronic Migraines (15+ headache days a month). See full Safety and Product Info, including Boxed Warning.