A Phase Ib/II, Multicentre, Double-blind, Randomised, Placebo-controlled, Dose Escalation and Dose-finding Study to Evaluate the Safety and Efficacy of IPN10200 in Improving the Appearance of Moderate to Severe Upper Facial Lines in Adults
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Ipsen
- 入组人数
- 727
- 试验地点
- 19
- 主要终点
- Incidence of serious adverse events (SAEs) at each dose
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy profile of increasing doses of Corabotase (also known as IPN10200) in comparison to placebo, with the aim to discover the doses(s) that offer the best efficacy/safety profile when used for the treatment of moderate to severe Upper Facial Lines.
This study will be conducted in three stages. The full study (including all stages) will have a maximum 727 participants.
Stage 1 (phase Ib & II)
- Step 1 (Phase Ib): a dose-escalation first-in-human step in participants with moderate to severe Glabellar Lines (GL)
- Step 2 (Phase II): dose ranging step in participants with moderate to severe GL as compared with Dysport
- Step 3 (Phase II): dose finding step in participants with moderate to severe GL as compared with Dysport, followed by an open label (OL) phase for the highest dose cohort to assess the long-term safety and efficacy of Corabotase. In the OL phase, participants may receive repeat administrations of Corabotase for up to three additional cycles (up to four treatment cycles in total during the study).
Stage 2 (phase II) - An evaluation of efficacy and safety of Corabotase in one of the following regions: GL + forehead lines (FHL), forehead lines (FHL) or lateral canthal lines (LCL)
Stage 3 (phase II)
- A safety and efficacy evaluation of Corabotase in all three regions (GL, FHL and LCL)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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 inclusion 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 Dusport/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.
研究组 & 干预措施
Dysport group (stage 1 / step 2 and 3 only)
干预措施: Dysport (Biological)
Corabotase group
Stage 1/Step 1: Several cohorts of participants will be randomized in a ratio of 3:1 (Corabotase:placebo)in a dose-escalation manner. The decision to escalate to the next dose for each cohort will be based on Data Monitoring Committee (DMC) recommendation.
Stage 1/Step 2: parallel dose-ranging manner Stage 1/Step 3: each cohort will include three treatment groups randomised in a ratio of 4:1:1 (Corabotase: placebo:dysport) The decision to escalate to the next dose for each cohort will be based on DMC recommendation .
Stage 2: the dose(s) chosen for administration in each region of the face will be selected on the basis of the intermediate analyses of Stage 1/Step 3. Participants will be randomised for each group in a ratio of 4:4:1 (Corabotase:Corabotase:placebo).
Stage 3: total dose for each region defined in Stages 1 and 2. Participants will be randomised for each group in a ratio of 3:1.
干预措施: Corabotase (Biological)
Placebo group
Stage 1/Step 1: Several cohorts of participants will be randomized in a ratio of 3:1 in a dose-escalation manner. The decision to escalate to the next dose for each cohort will be based on Data Monitoring Committee (DMC) recommendation.
Stage 1/Step 2: parallel dose-ranging manner Stage 1/Step 3: each cohort will include three treatment groups randomised in a ratio of 4:1:1 (Corabotase:Corabotase: placebo) The decision to escalate to the next dose for each cohort will be based on DMC recommendation.
Stage 2: the dose(s) chosen for administration in each region of the face will be selected on the basis of the intermediate analyses of Stage 1/Step 3. Participants will be randomised for each group in a ratio of 4:4:1 (Corabotase:Corabotase:placebo).
Stage 3: total dose for each region defined in Stages 1 and 2. Participants will be randomised for each group in a ratio of 3:1.(Corabotase:placebo)
干预措施: IPN10200 Placebo (Biological)
结局指标
主要结局
Incidence of serious adverse events (SAEs) at each dose
时间窗: From the baseline to the end of the study (9 months)
At Stage 1/Step 1, Stage 3
Incidence of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs)
时间窗: From the baseline to the end of the study (9 months)
At Stage 1/Step 1, Stage 3
Incidence of treatment emergent adverse events (TEAEs) at each dose
时间窗: From the baseline to the end of the study (9 months)
At Stage 1/Step 1, Stage 3
Incidence of serious adverse events (SAEs) at each dose
时间窗: From the baseline to the end of the study (9 months)
At Stage 1/Step 1, Stage 3
Incidence of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs)
时间窗: From the baseline to the end of the study (9 months)
At Stage 1/Step 1, Stage 3
Response to treatment as measured by the composite response of 2-grade improvement on Investigator's Live Assessment (ILA) at maximum contraction
时间窗: At Week 4
At stage 1/Step 2, Step 3; ILA: a validated 4-point photographic scale to assess the severity and appearance of the GLs at maximum frown and at rest where 0 is "no lines are noticeable" and 3 is "lines are extremely pronounced"
Response to treatment as measured by the composite response of 2-grade improvement on subject's self-assessment (SSA) at maximum contraction
时间窗: At Week 4
At Stage 1/Step 2 and Step 3; SSA: a validated 4-point categorical scale to assess the appearance of their Glabellar Lines (GLs) at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles".
Response to treatment as measured by the composite response of 2-grade improvement on ILA at maximum contraction on the forehead lines (FHL) area
时间窗: At Week 4
At Stage 2 for the glabellar lines (GL)+ FHL group
Response to treatment as measured by the composite response of 2-grade improvement on SSA at maximum contraction on the forehead lines (FHL) area
时间窗: At Week 4
At Stage 2 for the glabellar lines (GL)+ FHL group
Response to treatment as measured by the composite response of 2-grade improvement ILA at maximum contraction on the lateral canthal lines (LCL) area
时间窗: At Week 4
At stage 2 for the LCL group
Response to treatment as measured by the composite response of 2-grade improvement on SSA at maximum contraction on the LCL area
时间窗: At Week 4
At stage 2 for the LCL group
次要结局
- Time to onset of treatment response based on subject diary cards to evaluate the appearance of their lines(From the baseline to the end of the study (9 months))
- Satisfaction with facial appearance scale score on the Face-Q satisfaction scale(From the baseline to the end of the study (9 months))
- Presence of BoNT-A antibodies and titres (binding and neutralizing)(At Week 4 , Week 24 and Week 36)
- Response to treatment measured by the composite response of 2-grade improvement on ILA(From the baseline to the end of the study (9 months))
- Response to treatment as achieved by a score of "none" or "mild" as measured by the ILA at maximum contraction(From the baseline to the end of the study (9 months))
- Incidence, severity and nature of treatment emergent adverse events (TEAEs)(From baseline to the end of the study (9 months))
- Response to treatment measured by the composite response of 2-grade improvement on SSA(From the baseline to the end of the study (9 months))
- Response to treatment as measured by the reduction of ≥2 grades on the ILA at maximum contraction(From the baseline to the end of the study (9 months))
- Response to treatment as achieved by a score of "none" or "mild" as measured by the ILA at rest(From the baseline to the end of the study (9 months))
- Response to treatment as measured by the reduction of ≥2 grades on the SSA at maximum contraction(From the baseline to the end of the study (9 months))
- Duration of treatment response based on ILA and SSA at maximum contraction(From the baseline to the end of the study (9 months))
- Presence of IPN10200 antibodies and titres (binding and neutralizing)(At Week 4 , Week 24 and Week 36)
- Response to treatment as achieved by a score of "none" or "mild" as measured by the SSA at maximum contraction(From the baseline to the end of the study (9 months))
- Response to treatment as achieved by a score of "very satisfied" or "satisfied" on the Subject Level of Satisfaction (SLS)(From the baseline to the end of the study (9 months))
- Incidence, severity and nature of serious adverse events (SAEs)(From baseline to the end of the study (9 months))
- Incidence, severity and nature of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs)(From baseline to the end of the study (9 months))