Evaluation of Safety and Efficacy of IPN10200 in Adults with Moderate to Severe Upper Facial Lines: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2024-512782-14-00
- Protocol
- D-FR-10200-002
- Sponsor
- Ipsen Innovation
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and tolerability of increasing doses of a single treatment of IPN10200 compared with placebo in participants with moderate to severe glabellar lines (GL). Additionally, the study aims to assess the safety and efficacy of IPN10200 compared with placebo in improving the appearance of moderate to severe lines, including GL, forehead lines (FHL), and lateral canthal lines (LCL), as measured by the Investigator's Live Assessment (ILA) and Subject's Self-assessment (SSA) at maximum contraction at Week 4. This is clinically relevant as it addresses both the safety profile and the potential aesthetic benefits of IPN10200, which could offer a new therapeutic option for individuals seeking treatment for upper facial lines.
Secondary objectives include:
- Assessing the efficacy of IPN10200 compared with placebo in improving the appearance of moderate to severe upper facial lines (GL, FHL, and LCL) at maximum contraction at Week 4.
- Evaluating the efficacy of increasing and parallel doses of a single treatment cycle of IPN10200 compared with placebo (and/or Dysport) in the improvement of the appearance of moderate to severe lines treated (GL/LCL/FHL) at each post-treatment timepoint, assessed by the investigator and participant.
- Determining the time to onset of treatment response, safety, presence of IPN10200 antibodies, and overall satisfaction with facial appearance.
- Determining the duration of treatment response based on ILA and SSA at maximum contraction.
- Assessing the efficacy of up to two doses of IPN10200 compared to placebo in improving the appearance of FHL or LCL as measured by SSA at rest and maximum contraction.
- In the open-label phase, assessing the safety and tolerability of IPN10200 following repeat doses in improving the appearance of moderate to severe GL, efficacy profiles of repeat doses, time of retreatment, and presence of IPN10200 antibodies.
Participants
The clinical trial involves **participants** aged 18 to 65 years, both male and female, with a focus on the treatment of moderate to severe upper facial lines. The study population includes individuals who are capable of providing informed consent and are not residing in institutions by administrative or court order. Participants are required to have moderate or severe glabellar lines (GL), forehead lines (FHL), or lateral canthal lines (LCL) at maximum contraction, as assessed by both the Investigator's Live Assessment (ILA) and the Subject's Self-assessment (SSA) using a validated 4-point scale. The trial includes both male and female participants, with specific contraceptive requirements for those of childbearing potential. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on their ability to comply with study instructions and their dissatisfaction with their facial lines. Participants must not be employees of the sponsor or clinical research unit personnel directly affiliated with the study, nor immediate family members of such individuals. The study does not provide specific details on lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the safety and efficacy of IPN10200 in improving the appearance of moderate to severe upper facial lines in adults. The trial involves a dose escalation and dose-finding phase, with the primary objective of assessing the safety and tolerability of increasing doses of IPN10200 compared to placebo. The study will also evaluate the efficacy of IPN10200 in improving the appearance of facial lines, as measured by both the Investigator's Live Assessment (ILA) and the Subject's Self-assessment (SSA) at maximum contraction at Week 4.
The trial is expected to run from April 2021 to February 2028, with participants involved for a duration that includes multiple study visits. The sequence of study visits begins with an inclusion (screening) visit to determine eligibility based on criteria such as age, health status, and the severity of facial lines. Participants must be between 18 to 65 years of age and must not reside in an institution by administrative or court order. The screening visit is followed by baseline assessments and the administration of the study intervention. Subsequent follow-up visits are scheduled to monitor the incidence, severity, and nature of any treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), as well as to conduct vital signs checks, facial and physical examinations, and ECGs.
The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted to evaluate the response to treatment and any long-term effects. Participants may be withdrawn from the study early if they experience significant adverse events or if they fail to comply with study requirements. The trial's design ensures that all participants, including those receiving placebo, are treated with the same level of care and monitoring throughout the study duration.
Treatment
The clinical trial involves the administration of several treatments, including the experimental medication **IPN10200**, which is a **solution for injection** containing the active substance **Clostridium botulinum, neurotoxin serotype A/B**. This biological product is administered via **intramuscular injection**. The dosing schedule involves a single treatment with dose escalation to assess safety and efficacy. Participant compliance is monitored through regular assessments and follow-ups.
Another treatment used in the trial is **DYSPORT 300 UNITES SPEYWOOD**, a **poudre pour solution injectable** containing **botulinum toxin type A - haemagglutinin complex**. This product is also administered via **intramuscular use**. The pharmaceutical form is a **solution for injection**, and it serves as a comparator in the study. The administration schedule and dosage are aligned with standard practices for such treatments, ensuring consistency in the trial's methodology.
The study also includes a **placebo** treatment, referred to as **IPN10200 placebo**, which is administered via **intramuscular injection**. The placebo is used to maintain the double-blind nature of the trial, allowing for an unbiased assessment of the experimental treatment's efficacy and safety. The placebo is designed to mimic the administration process of the active treatments without containing any active substances.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the improvement in the appearance of moderate to severe upper facial lines in adults. The primary efficacy endpoint is the response to treatment, measured by a composite response of a 2-grade improvement on both the Investigator's Live Assessment (ILA) and Subject's Self-assessment (SSA) at maximum contraction on the studied area at Week 4. Secondary endpoints include the response to treatment as measured by the reduction of ≥2 grades on the ILA at maximum contraction at each post-treatment visit for each concerned facial area, and achieving a score of "none" or "mild" as measured by the ILA and SSA at maximum contraction and at rest at each post-treatment visit.
Additional secondary endpoints involve the time to onset of treatment response based on participant diary cards, the duration of treatment response, and satisfaction with facial appearance as assessed by the Face-Q satisfaction scale at specified post-treatment visits. The presence of IPN10200 antibodies and titres (binding and neutralising) will also be evaluated at certain post-treatment visits. Efficacy assessments will be conducted using validated scales and will occur at various timepoints throughout the study, including Week 4 and subsequent post-treatment visits. The trial will employ a double-blind, randomised, placebo-controlled design to ensure the reliability and validity of the efficacy data collected.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- Moderate or severe (Grade 2 or 3) GL (Stage 1) at maximum contraction at Baseline, as assessed by the ILA using a validated 4-point photographic scale.
- Moderate or severe (Grade 2 or 3) GL (Stage 1) at maximum contraction at Baseline, as assessed by the SSA using a validated 4-point categorical scale.
- Moderate or severe (Grade 2 or 3) FHL (Stage 2) at maximum contraction and moderate to severe GL at maximum contraction at Baseline or moderate to severe (Grade 2 or 3) LCL (Stage 2) at maximum contraction (Stage as assessed by the ILA using a 4-point photographic scale).
- Moderate or severe (Grade 2 or 3) FHL (Stage 3) at maximum contraction and moderate to severe GL at maximum contraction at Baseline and moderate to severe (Grade 2 or 3) LCL (Stage 3) at maximum contraction (Stage as assessed by the ILA using a 4-point photographic scale).
- Moderate or severe (Grade 2 or 3) FHL (Stage 2) at maximum contraction and moderate to severe GL maximum contraction at Baseline or moderate to severe (Grade 2 or 3) LCL (Stage 2) at maximum contraction as assessed by the SSA using a 4-point photographic scale.
- Moderate or severe (Grade 2 or 3) FHL (Stage 3) at maximum contraction and moderate to severe GL maximum contraction at Baseline and moderate to severe (Grade 2 or 3) LCL (Stage 3) at maximum contraction, as assessed by the SSA using a 4-point photographic scale.
- Dissatisfied or very dissatisfied (Grade 2 or 3) with their lines (Stages 1 to 3) at Baseline, as assessed by the SLS.
- Male and female participants (only female for Stage 1/Step 1). Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Capable of giving signed informed consent includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Participant has both the time and the ability to complete the study and comply with study instructions.
- Does not reside in an institution by administrative or court order.
- Is not a sponsor employee or clinical research unit personnel directly affiliated with the study or is not an immediate family member. Immediate family is defined as a spouse, parent, child or sibling whether biological or legally adopted.
Exclusion Criteria
- An active infection or other skin problems in the upper face including the GL, FHL, and LCL area (e.g. acute acne lesions or ulcers).
- A history of eyelid blepharoplasty or brow lift within the past 5 years
- A history of facial nerve palsy.
- Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin.
- Any known medical condition that may put the participant at increased risk in regard to exposure to BoNT of any serotype (i.e. myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, etc.)
- Has COVID-19 illness or a known positive SARS-CoV-2 test (Stage 1), or the presence of any other condition (e.g. neuromuscular disorder or other disorder that could interfere with neuromuscular function)
- Previous treatment with any BoNT serotype for Stage 1 / Step 1 or any recent treatment (within the past 9 months prior to baseline) with any BoNT serotype for Stage 1 / Step 2, Stage 1/Step 3, Stages 2 and 3. Participants treated in earlier Stages/Steps of the study must not be included in any later Stages/Steps.
- Any prior treatment with permanent fillers in the upper face including the GL, FHL and LCL area.
- Any prior treatment with long lasting dermal fillers or any permanent procedures in the upper face including the GL area within the past 3 years and/or skin abrasions/resurfacing (whatever the interventional technic used) within the past 5 years, or photo rejuvenation or skin/vascular laser intervention within the 12 months prior to Baseline.
- Any planned facial cosmetic surgery during the study.
- Use of concomitant therapy which, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study intervention. Therapy considered necessary for the participant’s welfare may be given at the discretion of the investigator.
- Use of medications that affect neuromuscular transmission, such as curare-like non depolarising agents, lincosamides, polymyxins, anticholinesterases, aminoglycoside antibiotics and systemic retinoids, within the past 30 days prior to Baseline are prohibited or a longer washout period of at least five half-lives might be required, as deemed appropriate by the investigator for longer-acting medications. Topical use of for example aminoglycoside medications or topical retinoids on the face apart from the area of injection would be acceptable.
- Use of any experimental device within 30 days or use of any treatment with an experimental drug within five times the documented terminal half-life of the respective drug or its metabolites or if the halflife is unknown within 30 days prior to the start of the study (prior to Baseline) and during the conduct of the study.
- Known positive for hepatitis B antigen, or hepatitis C virus antibody, or for human immunodeficiency virus (HIV) or a diagnosis of acquired immunodeficiency syndrome.
- Clinically diagnosed significant anxiety disorder, or any other significant psychiatric disorder (e.g. depression) that might interfere with the participant's participation in the study
- An inability to substantially lessen GL and/or horizontal forehead rhytids even by physically spreading them apart as determined by the investigator.
- Known allergy or hypersensitivity to BoNT, or any excipients of IPN10200 or Dysport/Azzalure, or allergy to cow's milk protein.
- A history of drug or alcohol abuse.
- Pregnant women, nursing women, premenopausal women or women of childbearing potential not willing to practice a highly effective form of contraception method.
- Male participants who are not vasectomized and who have female partners of childbearing potential and are not willing to use condoms with spermicide throughout study participation.
- Any uncontrolled systemic disease or other significant medical condition which would be harmful for the participant to be entered into the study or continue participation.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 06 Apr 2021 | 263 |
 Germany | Recruiting | 06 Apr 2021 | 508 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
IPN10200 placebo | Placebo | N/A | INTRAMUSCULAR INJECTION | — | — | N/A |
DYSPORT 300 UNITES SPEYWOOD, poudre pour solution injectable | Comparator | POUDRE POUR SOLUTION INJECTABLE | INTRAMUSCULAR USE | — | — | PRD2027924 |
IPN10200 | Test | SOLUTION FOR INJECTION | INTRAMUSCULAR INJECTION | — | — | PRD11447334 |