Evaluation of Botulinum Toxin Type A in Hidradenitis Suppurativa: A Randomized, Double-Blind, Placebo-Controlled, Within-Subject Study

The primary objective of this study is to evaluate the **treatment effect** of Botox in patients with **Hidradenitis Suppurativa** by assessing the reduction in disease activity. This is measured using the International Hidradenitis Suppurativa Severity Score System (IHS4) at the final follow-up, six months post-baseline. The IHS4 score is a recognized tool for quantifying the severity of Hidradenitis Suppurativa, categorizing the condition as mild (≤3 points), moderate (4-10 points), or severe (≥11 points). This measurement is clinically relevant as it provides a standardized method to assess the efficacy of the treatment in reducing disease severity.

Secondary objectives include evaluating various patient-reported outcomes and clinical parameters at baseline, three months, and six months. These include:

• Number of inflammatory and non-inflammatory nodules, and draining tunnels.
• Treatment satisfaction using a Numerical Rating Scale (NRS) from 0 (not satisfied) to 10 (very satisfied).
• Achievement of HiSCR50, a measure of clinical response.
• Hidradenitis Suppurativa Quality of Life (HiSQOL) score, ranging from 0 (no impact) to 60 (extreme impact).
• Dermatology Life Quality Index (DLQI) score, with a minimal clinically important difference (MCID) defined as a ≥4-unit decrease.
• Changes in pain, suppuration, and pruritus using NRS, with MCID for pain and pruritus considered as ≥30% and ≥1 point reduction from baseline.
• Patient-reported disease severity on an NRS from 0 (no disease) to 10 (worst imaginable disease).
• Patient willingness to recommend the procedure to others.

The clinical trial involves participants diagnosed with **Hidradenitis Suppurativa**, a chronic skin condition. The study population includes both male and female subjects, aged 18 years and older. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including having bilaterally affected areas with the same degree of severity and a confirmed diagnosis by a dermatologist. All participants must be cognitively intact to independently complete questionnaires. The trial does not involve a vulnerable population. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the therapeutic effect of **botulinum toxin type A** in patients with **hidradenitis suppurativa**. This study is a within-person, randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to commence on January 1, 2025, and conclude by January 1, 2028, with a maximum treatment period of 12 months for each participant. The primary objective is to assess the reduction in the International Hidradenitis Suppurativa Severity Score System (IHS4) score, with secondary endpoints including reductions in inflammatory nodules, treatment satisfaction, and quality of life improvements.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as bilateral disease severity and a confirmed diagnosis of **hidradenitis suppurativa**. Following the inclusion visit, participants will receive injections of either the active treatment or placebo. Follow-up visits will occur at regular intervals to monitor treatment effects and safety, with the final follow-up visit scheduled six months post-baseline to assess the primary endpoint. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any adverse events are addressed.

Participant involvement is expected to last up to 12 months, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with study procedures. The trial will utilize **sodium chloride** as a placebo comparator, with the active treatment being **botulinum toxin type A**. The study aims to provide robust data on the efficacy and safety of **botulinum toxin type A** in treating **hidradenitis suppurativa**, contributing valuable insights into potential therapeutic options for this condition.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **Sodium chloride** is used as a non-experimental treatment in the form of a **solution for injection**. It is administered via injection, with a maximum treatment period of 12 months. Sodium chloride serves as a placebo in this study, with no active therapeutic effect expected. The product is manufactured by AMGROS I/S and is classified under the ATC code V07AB, which denotes solvents and diluting agents, including irrigating solutions. The maximum daily and total dose amounts are set at 0 units, indicating its role as a placebo.

**Dysport**, containing the active substance **botulinum toxin type A - haemagglutinin complex**, is an experimental treatment in this trial. It is provided as a powder for solution for injection, with a maximum daily and total dose of 1000 units. The administration route is via injection, and the treatment period is capped at 12 months. Dysport is produced by INSTITUT PRODUITS SYNTHÈSE (IPSEN) AB and is categorized under the ATC code M03AX01, which pertains to botulinum toxin. This treatment is not a pediatric formulation and is not classified as an orphan drug.

**XEOMIN** is another experimental treatment, containing **clostridium botulinum neurotoxin type A (150KD), free of complexing proteins**. It is also provided as a powder for solution for injection, with a maximum daily and total dose of 250 units. The administration is conducted via injection, with a treatment duration of up to 12 months. Manufactured by MERZ PHARMACEUTICALS GMBH, XEOMIN is classified under the same ATC code as Dysport, M03AX01. This product is not intended for pediatric use and is not designated as an orphan drug.

**BOTOX**, containing **botulinum toxin type A**, is included as an experimental treatment. It is available as a powder for solution for injection, with a maximum daily and total dose of 400 units. The administration route is injection, and the treatment period is limited to 12 months. BOTOX is produced by ABBVIE A/S and shares the ATC classification M03AX01 with the other botulinum toxin products. Similar to the other treatments, it is not a pediatric formulation and does not have orphan drug status.

Efficacy in the clinical trial titled "Botox Treatment for Patients with Hidradenitis Suppurativa: A Within-Person, Randomized, Double-blind, Controlled Study" will be assessed primarily through the reduction of **IHS4** score. The IHS4 score is a recognized scoring system for evaluating the treatment effect in Hidradenitis Suppurativa (HS) studies. The primary endpoint is the difference in IHS4 score from baseline (IHS40) to the six-month follow-up (IHS46), with the treatment effect calculated as IHS46 - IHS40. The IHS4 score categorizes HS severity as mild (≤3 points), moderate (4-10 points), and severe (≥11 points).

Secondary endpoints include a reduction in the number of inflammatory and non-inflammatory nodules, draining tunnels, and improvements in patient-reported outcomes such as treatment satisfaction (NRS 0-10), HiSCR50 achievement, HiSQOL reduction, DLQI reduction, and reductions in pain, suppuration, pruritis, and patient-reported disease severity. Additionally, whether the patient would recommend the treatment to others will be evaluated. These efficacy parameters will be measured and collected at specified timepoints, including the final follow-up at six months post-baseline.