DaxibotulinumtoxinA for Blepharospasm

NCT07489430 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: 860263 (26-0164)2026-IST-DAXI-000345
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to provide real-world information about the duration, safety, and overall benefit of DaxibotulinumtoxinA (also called DAXI) treatment for adults living with blepharospasm (BSP), a condition that causes uncontrolled blinking or muscle spasms around the eyes, which can interfere with vision and daily activities. Specifically, it is being done to learn more about how well and how long DAXI works for treating adults with blepharospasm. This is a single-center, open-label, single-arm study, meaning everyone in the study will receive DAXI, and both participants and researchers will know what treatment is being given. The study will include 20 adult participants. Participants may receive two to three treatment cycles of DAXI injections over about 12 months. The timing between treatments will depend on how long each injection works for each person. Injections will be given at least every 90 days (3 months) but no later than every 180 days (6 months). Participants and their doctors will decide when another injection is needed based on symptom control using a tool called the Blepharospasm Severity Tracker Form (BSTF). To make the injections more comfortable, participants may use topical lidocaine cream, cooling spray, or another local anesthetic before injection. DAXI will be prepared by the injecting clinician or trained staff right before use. The medication is made by mixing a measured amount of DAXI powder with a small amount of sterile saline solution (salt water) to reach the correct concentration. The exact injection technique (including the dose, location, and number of injection sites) will be chosen by the injector based on each participant's needs, but treatment will only be given in specific facial muscles (corrugator, procerus, orbicularis oculi, and nasalis). The use of imaging tools such as electromyography (EMG) or ultrasound is optional and typically not required for injections around the eyes. The starting DAXI dose will be based on each participant's current or previous botulinum toxin treatment:

• If the participant was previously treated with onabotulinumtoxinA (Botox®), the same number of "units" will be used for DAXI (a 1:1 conversion).
• If the participant was previously treated with incobotulinumtoxinA (Xeomin®), the DAXI dose will be adjusted to about two-thirds of the previous incobotulinumtoxinA dose (a 1.5:1 conversion). If a participant experienced side effects such as droopy eyelids (ptosis), double vision (diplopia), or dry eyes with prior treatments, that information will help guide dosing decisions. For later injection cycles, the injector may adjust the dose or injection pattern based on how well the participant responds. Whenever possible, the same injector will perform all of a participant's treatments to keep results consistent. Participants will come to the clinic for in-person visits for most study assessments. After each DAXI injection, the peak effect (best response) will be evaluated about one month later, guided by the BSTF. These visits may be done remotely (via phone or video) when appropriate. The same schedule will be followed for future cycles. For the final treatment, this one-month check will occur unless the participant reports that the treatment's full effect happened sooner. The main goal (primary endpoint) of the study is to measure how long DAXI's effects last, specifically by tracking the median time until the next injection is needed. Other key goals (secondary endpoints) include:
• How long participants feel the treatment works
• How severe their blepharospasm symptoms are over time
• What side effects or safety concerns occur (adverse events)

Conditions

Blepharospasm of Both Eyelids; Blepharospasm of Left Eyelid; Blepharospasm of Right Eyelid; Blepharospasm, Benign Essential; Blepharospasm

Keywords

blepharospasm; botulinum toxin injections; parkinsonism; dystonia; daxibotulinumtoxinA

Outcome Measures

Primary Outcomes (2)

• First time to retreatment

  Time to retreatment (in days) with DAXI between the first and second study injection cycle.

  Outcome will be assessed during Visit 5 (2nd study injection visit) and reported at study conclusion. Visit 5 will take place for each individual subject between days 180 and 280.

• Final time to retreatment

  For patients who receive 3 study injection cycles with DAXI over 12 months, a second primary endpoint will be the time to retreatment (in days) between the second-to-last and last injection cycle (i.e., between DAXI cycles 2 and 3).

  Outcome will be assessed during Visit 7 (3rd study injection visit) and reported at study conclusion. Visit 7 will take place for each individual study subject between days 270 and 280.

Secondary Outcomes (11)

• Difference in time to return of symptoms after first DAXI cycle

  Outcome will be assessed during Visit 3 (1st study injection visit) and reported at study conclusion. Visit 3 will take place for each individual study subject between days 90 and 100.

• Difference in time to return of symptoms after final DAXI cycle

  Outcome will be assessed during Visit 5 (days 180-280) for subjects only receiving 2 injections during study participation, and during Visit 7 (days 270-280) for subjects receiving 3. Outcomes will be reported at study conclusion.

• Change in severity after first DAXI injection cycle

  Outcome will be assessed during Visit 4 (1st study injection peak effect assessment) and reported at study conclusion. Visit 4 will take place for each individual study subject between days 114 and 156.

• Change in severity after final DAXI injection cycle

  BSRS will be assessed during Visit 6 (days 200-340) for subjects only receiving 2 injections during study participation, and during Visit 8 (days 294-336) for subjects receiving 3. Outcomes will be reported at study conclusion.

• First change in the Patient Global Impression of Change (PGIC)

  Outcome will be assessed during Visit 4 (peak efficacy assessment of first study DAXI injection) taking place on days 114-156, and reported at study conclusion.

Other Outcomes (3)

• First change in craniocervical dystonia questionnaire

  Outcome will be assessed during Visit 4 (1st study injection peak effect assessment) and reported at study conclusion. Visit 4 will take place for each individual study subject between days 114 and 156.

• Final change in craniocervical questionnaire

  Outcome will be assessed during Visit 6 (days 200-340) for subjects only receiving 2 injections during study participation, and during Visit 8 (days 294-336) for subjects receiving 3. Outcomes will be reported at study conclusion.

• Average total DAXI doses at first and final study cycle

  Outcome will be assessed during Visit 5 (days 180-280) for subjects only receiving 2 injections during study participation, and during Visit 7 (days 270-280) for subjects receiving 3. Outcomes will be reported at study conclusion.

Study Arms (1)

Open label arm

EXPERIMENTAL

The study cohort will consist of adults with blepharospasm who previously received onabotulinumtoxinA or incobotulinumtoxinA and will transition to DAXI 12 weeks after their last botulinum toxin treatment. Each participant will receive a DAXI dose equivalent to their prior therapy, using a 1:1 conversion for onabotulinumtoxinA or a 1.5:1 conversion for incobotulinumtoxinA, adjusted if prior treatment caused excessive weakness or other side effects. Injections will be limited to muscles directly involved in blepharospasm (the orbicularis oculi, corrugators, procerus, and nasalis) and will use a dilution of 10 units per 0.1 mL. Subjects may use topical anesthetics to reduce injection pain, and efforts will ensure the same injector administers all treatments to maintain consistency.

Drug: Botulinum Neurotoxin Type A

Interventions

Botulinum Neurotoxin Type A DRUG

DaxibotulinumtoxinA (DAXI) for injection is a sterile, lyophilized powder containing 100 units of active daxibotulinumtoxinA per vial, along with inactive ingredients including RTP004, trehalose dihydrate, L-histidine, L-histidine hydrochloride, and polysorbate 20. It is reconstituted with Bacteriostatic Sodium Chloride Injection 0.9% (Pfizer) and stored at 2-8°C. DAXI will be prepared by trained injectors or staff, with all preparations documented. Experienced movement disorder neurologists will administer injections, primarily from UPenn's Parkinson's Disease and Movement Disorders Center. Dosing will follow prior treatment patterns using a 1:1 conversion from onabotulinumtoxinA or 1.5:1 from incobotulinumtoxinA, adjusted for prior adverse effects. Injection sites will be selected based on clinical presentation, with optional EMG or imaging guidance.

Also known as: daxibotulinumtoxinA, DAXI

Open label arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (18 years of age, or older)
• Clinical diagnosis of Blepharospasm that is disruptive enough to warrant ongoing clinical botulinum toxin injections and scoring ≥2 on the BSRS during screening. Blepharospasm may be focal (i.e. Benign essential blepharospasm), associated with non-drug-induced secondary cause (e.g., typical or atypical parkinsonism) or as part of a diagnosis of segmental or generalized dystonia involving the upper cranial region, if blepharospasm is the only indication requiring botulinum toxin injections.
• Currently receiving onabotulinumtoxinA or incobotulinumtoxinA for the treatment of blepharospasm with: 1) documented duration of benefit \<12 weeks from most recent injection; and 2) no further dose escalation possible or advised due to side effect risk (e.g., ptosis, diplopia, etc.), as determined by treating neurologist; and 3) ability to provide informed consent and comply with study procedures, or subject has a reliable caregiver/proxy.
• Written informed consent including authorization to release health information.

You may not qualify if:

• Tardive or medication-induced blepharospasm, as well as psychogenic/functional blepharospasm.
• Active ocular pathology interfering with evaluation or injection safety.
• Neuromuscular junction or motor neuron disorders (e.g., myasthenia gravis, Lambert-Eaton Myasthenic Syndrome, Amyotrophic Lateral Sclerosis, etc.).
• Known hypersensitivity to botulinum toxin or formulation components.
• Pregnant or breastfeeding women (including those who are found to be pregnant after a positive pregnancy test at Screening), women who are hoping to get pregnant over the upcoming 15 months, or women of childbearing potential who are unwilling to use contraception while enrolled in the BLEXI study.
• Any signal suggestive of active suicidality, as per C-SSRS at screening.
• Subjects who have undergone Deep Brain Stimulation (DBS) surgery for the management of blepharospasm and are not willing to keep the DBS settings unchanged for the duration of the trial.
• History of primary or secondary non-response to BoNT-A injections, particularly those known to have neutralizing antibodies to BoNT-A.
• Subjects on oral medications for dystonia (e.g., anticholinergics, muscle relaxants, benzodiazepines, dopamine depleter) who have not been stable on their regimen for at least 4 weeks prior to Screening, or who are not willing to keep them stable for the duration of the trial.
• Use of aminoglycoside antibiotics, polymyxins, lincosamides (e.g., clindamycin), or other agents that might interfere with neuromuscular transmission (e.g., curare-like drugs, quinidine, magnesium sulfate, anticholinesterases, succinylcholine chloride) within 14 days prior to Screening.
• History of severe (stage 3) chronic obstructive pulmonary disease, or unstable pulmonary disease within 30 days prior to Screening.
• History of chronic or recurrent hypokalemia.
• History of congestive heart failure (New York Heart Association Class III or IV), Torsade de Pointe (TdP), and/or Long QT Syndrome.
• Subjects in an investigational drug or device study within the last 30 days prior to Screening.
• Active skin infections at the injection sites which would put the subject at increased risk of morbidity with BoNT injections

Sponsors & Collaborators

• University of Pennsylvania: lead
• Revance Therapeutics, Inc.: collaborator

Study Sites (1)

Parkinson Disease and Movement Disorders Center at the University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (4)

• Dutton JJ, Fowler AM. Botulinum toxin in ophthalmology. Surv Ophthalmol. 2007 Jan-Feb;52(1):13-31. doi: 10.1016/j.survophthal.2006.10.003.

  PMID: 17212988 BACKGROUND

• Garcia-Murray E, Velasco Villasenor ML, Acevedo B, Luna S, Lee J, Waugh JM, Hornfeldt CS. Safety and efficacy of RT002, an injectable botulinum toxin type A, for treating glabellar lines: results of a phase 1/2, open-label, sequential dose-escalation study. Dermatol Surg. 2015 Jan;41 Suppl 1:S47-55. doi: 10.1097/DSS.0000000000000276.

  PMID: 25548845 BACKGROUND

• Aoki KR, Guyer B. Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions. Eur J Neurol. 2001 Nov;8 Suppl 5:21-9. doi: 10.1046/j.1468-1331.2001.00035.x.

  PMID: 11851731 BACKGROUND

• Defazio G, Hallett M, Jinnah HA, Conte A, Berardelli A. Blepharospasm 40 years later. Mov Disord. 2017 Apr;32(4):498-509. doi: 10.1002/mds.26934. Epub 2017 Feb 10.

  PMID: 28186662 BACKGROUND

MeSH Terms

Conditions

Benign essential blepharospasm; Blepharospasm; Parkinsonian Disorders; Dystonia

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Eyelid Diseases; Eye Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This Phase 2, open-label, single-center trial will assess the efficacy and safety of daxibotulinumtoxinA (DAXI) for adults with blepharospasm, either isolated, part of segmental dystonia, or associated with parkinsonian syndromes. The sponsor considers the study low-risk, using an FDA-approved drug for a non-significant modification of use. Twenty adults who are already receiving onabotulinumtoxinA or incobotulinumtoxinA will be enrolled and switched to DAXI 12 weeks after their last injection. DAXI will be injected only into muscles directly involved in BSP. The primary endpoints are time to retreatment between injection cycles (as a marker of duration of effect). Efficacy will be measured using BSRS, CDQ-24, global impression scales, and satisfaction questionnaires. Safety evaluations include neurological exams, pregnancy tests, C-SSRS, and monitoring for adverse events.

Study Record Dates

• First Submitted: March 4, 2026
• First Posted: March 24, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)