Efficacy and Safety Evaluation of IPN10200 in Adult Cervical Dystonia: A Phase II Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to assess the **efficacy** of IPN10200 treatment compared to placebo in reducing symptoms of **Cervical Dystonia** (CD) at Week 4 in adult participants. This is clinically relevant as it aims to provide evidence on the potential therapeutic benefits of IPN10200, which could lead to improved management of CD, a condition characterized by involuntary muscle contractions in the neck.

Secondary objectives include: - Evaluating the efficacy of IPN10200 over time in reducing CD symptoms compared to placebo. - Assessing whether IPN10200 reduces pain, disability, and severity of symptoms in CD patients. - Evaluating the return of symptoms and the overall health impacts of CD. - Assessing the safety and tolerability of IPN10200. - Determining if IPN10200 improves illness symptoms and reduces illness severity as assessed by both clinicians and participants.

The clinical trial involves a total of **41 participants** diagnosed with **Cervical Dystonia**, a condition characterized by involuntary muscle contractions in the neck, head, and shoulder areas. The study population includes both male and female adults, with an age range that corresponds to categories 3 and 4, typically encompassing individuals from young adulthood to middle age. Participants were selected based on a clinical diagnosis of isolated Cervical Dystonia with at least moderate severity, as measured by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The trial does not include a vulnerable population. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The study aims to evaluate the efficacy of IPN10200 treatment compared to placebo in reducing symptoms of Cervical Dystonia at Week 4.

The clinical trial is a Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the efficacy and safety of **IPN10200** as a treatment for **cervical dystonia** in adult participants. The trial aims to assess the efficacy of IPN10200 compared to placebo in reducing cervical dystonia symptoms at Week 4. The study involves the administration of IPN10200, a solution for injection containing **clostridium botulinum, neurotoxin serotype A/B**, via intramuscular use. The trial is expected to commence recruitment on June 12, 2025, and conclude by November 5, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a clinical diagnosis of isolated cervical dystonia with moderate severity. The baseline visit (Day 1) will involve randomization and administration of the study drug or placebo. Follow-up visits will be scheduled at various time points post-injection, with primary efficacy assessed at Week 4. Secondary endpoints will be evaluated at all scheduled timepoints until Week 36, including changes in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores and other clinical assessments.

The expected length of participant involvement is approximately 36 weeks, with conditions for early termination including the occurrence of serious adverse events or clinically significant changes in laboratory parameters, vital signs, or neurological examinations. Participants will also be monitored for the emergence of suicidal ideation or behavior using the Columbia Suicide Severity Rating Scale (C-SSRS). The end-of-study visit will involve a comprehensive evaluation of the participant's condition and any adverse events experienced during the trial.

The clinical trial involves the administration of **IPN10200**, an experimental medication formulated as a **solution for injection**. The active substance in IPN10200 is **Clostridium botulinum, neurotoxin serotype A/B**, which is classified as a protein of other origin. The medication is intended for **intramuscular use**. The dosing regimen specifies a maximum treatment period of one unit of time, with no specified maximum daily or total dose amount. The administration schedule and participant compliance will be monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** of IPN10200 is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is designed to mimic the experimental treatment in appearance and administration method, although it contains no active substance. The placebo serves as a control to evaluate the efficacy and safety of IPN10200 in reducing symptoms of **Cervical Dystonia** in adult participants. The study's design ensures that neither the participants nor the investigators are aware of the treatment assignments, maintaining the integrity of the trial's outcomes.

The efficacy of IPN10200 in treating **Cervical Dystonia** will be assessed through a Phase II, multicentre, randomised, double-blind, parallel-group, placebo-controlled study. The primary endpoint for evaluating efficacy is the change from baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at Week 4. This scale is a validated tool used to measure the severity of symptoms in patients with Cervical Dystonia.

Secondary endpoints include changes from baseline in the TWSTRS total score at all scheduled timepoints post-injection until Week 36, as well as changes in the TWSTRS-Pain, TWSTRS-Disability, and TWSTRS-Severity subscales. Additional assessments involve the daily Numerical Rating Scale (NRS) score, time to onset of pain reduction, and time to return of symptoms in responders. Patient-reported outcomes such as the Clinical Global Impression of Severity (CGI-S) and Change (CGI-C) scores, Patients' Global Impression of Severity (PGI-S) and Change (PGI-C) scores, and the Cervical Dystonia Impact Profile (CDIP-58) total score will also be evaluated.

The study will monitor the percentage of participants experiencing adverse events, including treatment-emergent adverse events, serious adverse events, and adverse events of special interest. Clinically significant changes from baseline in laboratory parameters, vital signs, neurological/physical examinations, and 12-lead Electrocardiogram (ECG) readings will be reported. The emergence of suicidal ideation or behavior will be assessed using the Columbia Suicide Severity Rating Scale (C-SSRS). Additionally, the presence of binding and neutralizing antibodies to IPN10200 will be evaluated at all timepoints post-injection until Week 36.