Cervical Dystonia
Conditions
Brief summary
This Phase 2 trial will evaluate the safety and efficacy of ABP-450 for the treatment of cervical dystonia in adults. The study will enroll 60 patients across approximately 30 sites in the United States. Study subjects will be divided evenly across a low dose group, a medium dose group, a high dose group, and a placebo group for one treatment cycle.
Detailed description
This Phase 2 trial will evaluate the safety and efficacy of ABP-450 for the treatment of cervical dystonia in adults. The study will enroll 60 patients across approximately 30 sites in the United States. Study subjects will be divided evenly across a low dose, a medium dose group, a high dose and placebo group for one treatment cycle.
Interventions
DRUGABP-450
ABP-450 (prabotulinumtoxinA) contains a 900kDA botulinum toxin type-A complex produced by the bacterium Clostridium botulinum.
DRUGPlacebo
0.9% sodium chloride, sterile, unpreserved, USP/Ph.Eur.
Sponsors
PPD Development, LP
AEON Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The investigator, study nurse/other study personnel, and patients will be blinded to the treatment group. An appropriately trained person will reconstitute investigational product, fill masked syringes and provide them to the blinded investigator, but will not perform any assessments with the patient.
Intervention model description
Approximately 60 patients will be randomized in a 1:1:1:1 ratio and receive one of the four treatments: ABP-450 low dose, ABP-450 mid dose, ABP-450 high dose, or placebo via intramuscular injection into affected neck muscles.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients between 18 and 75 years of age (inclusive) 2. A clinical diagnosis of cervical dystonia (ie, spasmodic torticollis) defined by: * TWSTRS total score ≥20 * TWSTRS severity score ≥10 * TWSTRS disability score ≥3 * TWSTRS pain score ≥1 3. On a stable dose of medications (if any) used for focal dystonia treatment (eg, anticholinergics and benzodiazepines) for at least 3 months prior to and expected throughout the study duration 4. For pre-treated patients only: Source documentation (eg, patient history) of the last 2 consecutive injection sessions with a botulinum toxin type A 5. For pre-treated patients only: At least 16 weeks must have passed between the last injection with botulinum toxin for cervical dystonia and baseline treatment (patients can be screened at Week 15 but cannot be enrolled until 16 weeks \[for Day 0 injection\]) 6. Provided written informed consent to being treated for cervical dystonia with ABP-450 7. Stated willingness to comply with all study procedures, including attendance at the study center for all study visits as scheduled and have technological capabilities to have televisits
Exclusion criteria
1. Traumatic torticollis or tardive torticollis 2. Predominant retrocollis or anterocollis 3. Myotomy or denervation surgery in the affected muscles (eg, peripheral denervation and/or spinal cord stimulation) 4. Hypersensitivity to human serum albumin, sucrose, or botulinum toxin type A 5. Previous treatment for cervical dystonia with rimabotulinumtoxin B 6. Diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease that might interfere with the trial 7. Current swallowing disorder of any origin (dysphagia scale ≥3, ie, severe, with swallowing difficulties and requiring a change in diet) 8. Marked limitation on passive range of motion that suggests contractures or other structural abnormality, eg, cervical contractures or cervical spine syndrome 9. Treatment with botulinum toxins of any type for any indication other than cervical dystonia within 16 weeks prior to baseline and during the study 10. Medical or psychiatric conditions that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study 11. Participation in another interventional study during participation in this study 12. Pregnant or lactating females, or females of child-bearing potential not willing to use an acceptable method of contraception (ie, intrauterine device, barrier methods with spermicide, or abstinence) 13. For pre-treated patients only: The patient's most recent injection with botulinum toxin exceeding the number of units specified as follows: * OnabotulinumtoxinA (BOTOX®): \>300 units * IncobotulinumtoxinA (Xeomin®): \>300 units * AbobotulinumtoxinA (Dysport®): \>750 units
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Related Serious Adverse Events | Baseline up to 20 Weeks | The primary safety endpoint will be the number of participants with treatment-related serious adverse events since the start of treatment by Treatment Group when dosed with placebo, ABP-450 (low dose), ABP-450 (medium d dose), or ABP-450 (high dose). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Subscale Score of Disability of the Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | Baseline to Week 4 | The Disability subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is used to assess the severity of disability in cervical dystonia. The disability subscale has a minimum score of 0 and maximum score of 30, where higher scores represent worse outcomes. |
| Mean Change in the Subscale Score of Pain of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | Baseline to Week 4 | The Pain subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is used to assess the severity of pain in cervical dystonia. The pain subscale has a minimum score of 0 and maximum score of 20, where higher scores represent worse outcomes. |
| Mean Change of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total Score From Baseline to Week 4 | Baseline to Week 4 | The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scale is used to assess the severity of cervical Dystonia. The TWSTRS-total score has a minimum score of 0 and a maximum score of 85, where higher scores represent worse outcomes. It comprises 3 subscales, which are summated to get the total score: the Torticollis Severity Scale (minimum score of 0, maximum score of 35), the Disability Scale (minimum score of 0, maximum score of 30), and the Pain Scale (minimum score of 0, maximum score of 20). |
| Mean Change in Patient Global Impression of Change (PGI-C) From Baseline to Week 4 | Baseline to Week 4 | The PGI-C enables the patient to rate changes in their perception of their general health status over the duration of the assessment via a 7-point scale ranging from much improved to much worse. The 7-point scale range is much improved (+3) to much worse (-3) with no change at 0. The mean change in the subject's assessment of the change in clinical status since the start of treatment measured by the Patients' Global Impression of Change (PGI-C) Scale was assessed by Treatment Group at Week 4. |
| Mean Change in Clinical Global Impression of Change (CGI-C) From Baseline to Week 4 | Baseline to Week 4 | The CGI-C enables the patient to rate changes in their perception of their general health status over the duration of the assessment via a 7-point scale ranging from much improved to much worse. The 7-point scale range is much improved (+3) to much worse (-3) with no change at 0. The mean change from Baseline in the Clinical Global Impression of Change (CGI-C) Score was assessed by Treatment Group at Week 4. |
| Mean Change in the Subscale Score of Severity of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | Baseline to Week 4 | The Severity subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is used to assess the severity of torticollis in cervical dystonia. The severity subscale has a minimum score of 0 and maximum score of 35, where higher scores represent worse outcomes. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 25 sites in the U.S. between March 29, 2021 and July 11, 2021.
Pre-assignment details
Of the 70 participants screened, 61 were randomized. There were 59 participants randomized and dosed, and 57 of them were included in the modified full analysis set (mFAS) for the efficacy analysis.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (0.9% unpreserved saline) - Intramuscular injections into affected neck muscles. | 14 |
| ABP-450 - 150U ABP-450 Low Dose - Intramuscular injections into affected neck muscles. | 14 |
| ABP-450 - 250U ABP-450 Medium Dose - Intramuscular injections into affected neck muscles. | 14 |
| ABP-450 - 350U ABP-450 High Dose - Intramuscular injections into affected neck muscles. | 15 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 3 | 4 | 1 | 4 |
| Overall Study | Other reasons | 1 | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | ABP-450 - 150U | Total | ABP-450 - 350U | ABP-450 - 250U | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 12.97 | 56.2 years STANDARD_DEVIATION 12.09 | 55.3 years STANDARD_DEVIATION 11.39 | 54.6 years STANDARD_DEVIATION 13.61 | 59.3 years STANDARD_DEVIATION 11.06 |
| Baseline TWSTRS-Total Score | 44.30 units on a scale STANDARD_DEVIATION 6.093 | 42.47 units on a scale STANDARD_DEVIATION 8.962 | 43.62 units on a scale STANDARD_DEVIATION 9.847 | 42.20 units on a scale STANDARD_DEVIATION 11.585 | 39.68 units on a scale STANDARD_DEVIATION 7.525 |
| Duration of Cervical Dystonia | 14.58 years STANDARD_DEVIATION 10.799 | 12.26 years STANDARD_DEVIATION 9.421 | 11.53 years STANDARD_DEVIATION 7.175 | 7.36 years STANDARD_DEVIATION 6.464 | 14.83 years STANDARD_DEVIATION 11.134 |
| Previous treatment with BOTOX® | 9 Participants | 40 Participants | 10 Participants | 11 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 14 Participants | 52 Participants | 14 Participants | 11 Participants | 13 Participants |
| Sex: Female, Male Female | 7 Participants | 39 Participants | 12 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 18 Participants | 3 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 16 | 0 / 15 |
| other Total, other adverse events | 9 / 14 | 8 / 14 | 12 / 16 | 11 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 16 | 0 / 15 |
Outcome results
Primary
Number of Participants With Treatment-Related Serious Adverse Events
The primary safety endpoint will be the number of participants with treatment-related serious adverse events since the start of treatment by Treatment Group when dosed with placebo, ABP-450 (low dose), ABP-450 (medium d dose), or ABP-450 (high dose).
Time frame: Baseline up to 20 Weeks
Population: All treated patients are accounted for in the Treatment-related Serious Adverse Events data table including the two patients with changes in background medications.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Related Serious Adverse Events | 0 Participants |
| ABP-450 - 150U | Number of Participants With Treatment-Related Serious Adverse Events | 0 Participants |
| ABP-450 - 250U | Number of Participants With Treatment-Related Serious Adverse Events | 0 Participants |
| ABP-450 - 350U | Number of Participants With Treatment-Related Serious Adverse Events | 0 Participants |
Secondary
Mean Change in Clinical Global Impression of Change (CGI-C) From Baseline to Week 4
The CGI-C enables the patient to rate changes in their perception of their general health status over the duration of the assessment via a 7-point scale ranging from much improved to much worse. The 7-point scale range is much improved (+3) to much worse (-3) with no change at 0. The mean change from Baseline in the Clinical Global Impression of Change (CGI-C) Score was assessed by Treatment Group at Week 4.
Time frame: Baseline to Week 4
Population: Two patients were excluded from the analysis due to a change in their background medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in Clinical Global Impression of Change (CGI-C) From Baseline to Week 4 | 3.9 units on a scale | Standard Error 0.33 |
| ABP-450 - 150U | Mean Change in Clinical Global Impression of Change (CGI-C) From Baseline to Week 4 | 2.3 units on a scale | Standard Error 0.32 |
| ABP-450 - 250U | Mean Change in Clinical Global Impression of Change (CGI-C) From Baseline to Week 4 | 2.0 units on a scale | Standard Error 0.33 |
| ABP-450 - 350U | Mean Change in Clinical Global Impression of Change (CGI-C) From Baseline to Week 4 | 2.7 units on a scale | Standard Error 0.31 |
Secondary
Mean Change in Patient Global Impression of Change (PGI-C) From Baseline to Week 4
The PGI-C enables the patient to rate changes in their perception of their general health status over the duration of the assessment via a 7-point scale ranging from much improved to much worse. The 7-point scale range is much improved (+3) to much worse (-3) with no change at 0. The mean change in the subject's assessment of the change in clinical status since the start of treatment measured by the Patients' Global Impression of Change (PGI-C) Scale was assessed by Treatment Group at Week 4.
Time frame: Baseline to Week 4
Population: Two patients were excluded from the analysis due to a change in their background medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in Patient Global Impression of Change (PGI-C) From Baseline to Week 4 | 4.0 units on a scale | Standard Error 1.11 |
| ABP-450 - 150U | Mean Change in Patient Global Impression of Change (PGI-C) From Baseline to Week 4 | 2.6 units on a scale | Standard Error 0.31 |
| ABP-450 - 250U | Mean Change in Patient Global Impression of Change (PGI-C) From Baseline to Week 4 | 2.2 units on a scale | Standard Error 0.32 |
| ABP-450 - 350U | Mean Change in Patient Global Impression of Change (PGI-C) From Baseline to Week 4 | 2.7 units on a scale | Standard Error 0.3 |
Secondary
Mean Change in the Subscale Score of Disability of the Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4
The Disability subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is used to assess the severity of disability in cervical dystonia. The disability subscale has a minimum score of 0 and maximum score of 30, where higher scores represent worse outcomes.
Time frame: Baseline to Week 4
Population: Two patients were excluded from the analysis due to a change in their background medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the Subscale Score of Disability of the Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 1.02 score on a scale | Standard Error 1.11 |
| ABP-450 - 150U | Mean Change in the Subscale Score of Disability of the Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 4.53 score on a scale | Standard Error 1.09 |
| ABP-450 - 250U | Mean Change in the Subscale Score of Disability of the Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 4.24 score on a scale | Standard Error 1.14 |
| ABP-450 - 350U | Mean Change in the Subscale Score of Disability of the Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 2.62 score on a scale | Standard Error 1.06 |
Secondary
Mean Change in the Subscale Score of Pain of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4
The Pain subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is used to assess the severity of pain in cervical dystonia. The pain subscale has a minimum score of 0 and maximum score of 20, where higher scores represent worse outcomes.
Time frame: Baseline to Week 4
Population: Two patients were excluded from the analysis due to a change in their background medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the Subscale Score of Pain of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 1.27 score on a scale | Standard Error 1.1 |
| ABP-450 - 150U | Mean Change in the Subscale Score of Pain of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 3.56 score on a scale | Standard Error 1.05 |
| ABP-450 - 250U | Mean Change in the Subscale Score of Pain of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 3.58 score on a scale | Standard Error 1.08 |
| ABP-450 - 350U | Mean Change in the Subscale Score of Pain of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 3.69 score on a scale | Standard Error 1.02 |
Secondary
Mean Change in the Subscale Score of Severity of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4
The Severity subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is used to assess the severity of torticollis in cervical dystonia. The severity subscale has a minimum score of 0 and maximum score of 35, where higher scores represent worse outcomes.
Time frame: Baseline to Week 4
Population: Two patients were excluded from the analysis due to a change in their background medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the Subscale Score of Severity of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 1.91 score on a scale | Standard Error 0.91 |
| ABP-450 - 150U | Mean Change in the Subscale Score of Severity of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 5.89 score on a scale | Standard Error 0.91 |
| ABP-450 - 250U | Mean Change in the Subscale Score of Severity of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 2.94 score on a scale | Standard Error 0.97 |
| ABP-450 - 350U | Mean Change in the Subscale Score of Severity of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) From Baseline to Week 4 | 3.45 score on a scale | Standard Error 0.87 |
Secondary
Mean Change of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total Score From Baseline to Week 4
The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scale is used to assess the severity of cervical Dystonia. The TWSTRS-total score has a minimum score of 0 and a maximum score of 85, where higher scores represent worse outcomes. It comprises 3 subscales, which are summated to get the total score: the Torticollis Severity Scale (minimum score of 0, maximum score of 35), the Disability Scale (minimum score of 0, maximum score of 30), and the Pain Scale (minimum score of 0, maximum score of 20).
Time frame: Baseline to Week 4
Population: Two patients were excluded from the analysis due to a change in their background medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total Score From Baseline to Week 4 | 3.57 score on a scale | Standard Error 2.67 |
| ABP-450 - 150U | Mean Change of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total Score From Baseline to Week 4 | 14.01 score on a scale | Standard Error 2.63 |
| ABP-450 - 250U | Mean Change of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total Score From Baseline to Week 4 | 11.28 score on a scale | Standard Error 2.7 |
| ABP-450 - 350U | Mean Change of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total Score From Baseline to Week 4 | 9.92 score on a scale | Standard Error 2.54 |