The purpose of this study is to assess the safety and efficacy profile of increasing doses of 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 IPN10200. In the OL phase, participants may receive repeat administrations of IPN10200 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 IPN10200 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 IPN10200 in all three regions (GL, FHL and LCL)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
727
Stage 1: Several different doses will be administrated in a dose-escalation manner. One single injection will be injected locally into several sites across the glabellar region. Stage 2: One single injection will be injected locally into several sites across the glabellar, forehead and lateral Canthal regions. Stage 3: One single injection will be injected locally into several sites across the upper facial area.
Stage 1: One single injection of study intervention will be injected locally into several sites across the glabellar region. Stage 2: One single injection will be injected locally into several sites across the glabellar, forehead and lateral Canthal regions. Stage 3: One single injection will be injected locally into several sites across the upper facial area.
Single administration of study intervention in stage 1 / step 2 and 3 only
MEDITI - Clinique Del Mar
Antibes, France
Aimed S.A.S
Lyon, France
Clinique de Chirurgie Esthétique Iéna
Paris, France
Interdisciplinary Study Association
Kassel, State of Berlin, Germany
CRS Clinical Research Services Berlin GMBH
Berlin, Germany
Interdisciplinary Study Association
Berlin, Germany
ROSENPARK RESEARCH GmbH
Darmstadt, Germany
Privatpraxis Dr. Hilton & Partner
Düsseldorf, Germany
Fachbereich Chemie Institut für Biologie und Molekularbiologie Studiengang Kosmetikwissenschaft
Hamburg, Germany
Dermatologische Gemeinschaftspraxis Blankenfelde-Mahlow
Mahlow, Germany
Incidence of treatment emergent adverse events (TEAEs) at each dose
At Stage 1/Step 1, Stage 3
Time frame: From the baseline to the end of the study (9 months)
Incidence of serious adverse events (SAEs) at each dose
At Stage 1/Step 1, Stage 3
Time frame: From the baseline to the end of the study (9 months)
Incidence of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs)
At Stage 1/Step 1, Stage 3
Time frame: From the baseline to the end of the study (9 months)
Response to treatment at Stage 2 for the FHL group
Measured by the composite response of ≥ 2-grade improvement on Investigator's Live Assessment (ILA) and subject's self-assessment (SSA) at maximum contraction on the forehead lines: ILA: a validated 4-point photographic scale to assess the severity and appearance of the Forehead Lines (FHL) at maximum frown and at rest where 0 is "none" and 3 is "severe" SSA: a validated 4-point categorical scale to assess the appearance of their FHLs at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles"
Time frame: At Week 4
Response to treatment at Stage 2 for the glabellar lines (GL)+ FHL group
Measured by the composite response of ≥ 2-grade improvement on ILA and SSA at maximum contraction on the forehead lines (FHL) area: ILA: a validated 4-point photographic scale to assess the severity and appearance of the GLs and FHLs at maximum frown and at rest where 0 is "none" and 3 is "severe" SSA: a validated 4-point categorical scale to assess the appearance of their GLs and FHLs at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles"
Time frame: At Week 4
Response to treatment at Stage 2 for the LCL group
Measured by the composite response of ≥ 2-grade improvement ILA and SSA at maximum contraction on both sides of the lateral canthal lines (LCL) area: ILA: a validated 4-point photographic scale to assess the severity and appearance of the LCLs at maximum frown and at rest where 0 is "none" and 3 is "severe" SSA: a validated 4-point categorical scale to assess the appearance of their LCLs at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles"
Time frame: At Week 4
Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs
Double Blind phase. Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator.
Time frame: From the baseline to the end of the study (6 years, 5 months)
Percentage of participants with clinically significant Change from baseline in 12-lead Electrocardiogram (ECG) readings
Double Blind phase.
Time frame: From the baseline to the end of the study (6 years, 5 months)
Percentage of participants with clinically significant change from baseline in facial and focused neurological/physical examination.
Double Blind phase. Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator.
Time frame: From the baseline to the end of the study (6 years, 5 months)
Percentage of participants response to treatment.
For all stages. Measured by the composite response of ≥ 2-grade improvement on ILA and SSA for each concerned facial area in each respective stage (GL/LCL/FHL) ILA: a validated 4-point photographic scale to assess the severity and appearance of the GLs/LCLs/FHLs in each respective stage at maximum frown and at rest where 0 is "no lines are noticeable" and 3 is "lines are extremely pronounced" SSA: a validated 4-point categorical scale to assess the appearance of their GLs/LCLs/FHLs in each respective stage at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles"
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Percentage of participants response to treatment as measured by the reduction of ≥1 grade on the ILA at maximum contraction for each concerned facial area
For all stages.
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Percentage of participants with clinically significant change from baseline in facial and focused neurological/physical examination
For all stages. Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator.
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Percentage of participants response to treatment as achieved by a score of "none" or "mild" as measured by the ILA at rest on each facial area
For all stages
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Percentage of participants response to treatment as measured by the reduction of ≥1 grade on the SSA at maximum contraction for each concerned facial area
For all stages.
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Percentage of participants response to treatment as achieved by a score of "none" or "mild" as measured by the SSA at maximum contraction for each concerned facial area.
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Stage 2 and Stage 3.
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Duration of treatment response based on ILA and SSA at maximum contraction for each concerned facial area
For all stages.
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Response to treatment as achieved by a score of "very satisfied" or "satisfied" on the Subject Level of Satisfaction (SLS)
Time frame: From the baseline to the end of the study (9 months)
Time to onset of treatment response based on subject diary cards to evaluate the appearance of their lines for each concerned facial area
For all stages.
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Satisfaction with facial appearance, measured by Facial Appearance Overall scale score on the Face-Q satisfaction scale
Stage 3. Face Q is a participant-reported outcome instrument to evaluate the experience and outcomes of aesthetic facial procedures from the participant's perspective. The Face Q instrument is composed of over 40 scales, covering four domains (Satisfaction with Facial Appearance, Health Related Quality of Life, Adverse Effects, and Process of Care).
Time frame: From the baseline to the end of the study (up to 6 years, 5 months)
Satisfaction with facial appearance, measured by FACE-Q Short Form Facial Appearance scale score.
Stage 3. The FACE-Q Short Form Facial Appearance scale is a participant-reported outcome instrument. It asks how dissatisfied or satisfied the participant is with their upper facial lines (UFL) (GL+FHL+LCL). The scale ranges from very dissatisfied to very satisfied.
Time frame: From the baseline to the end of the study (6 years, 5 months)
Incidence, severity and nature of treatment emergent adverse events (TEAEs)
All stages (except Stage 1/Step 1)
Time frame: From baseline to the end of the study (up to 6 years, 5 months)
Incidence, severity and nature of serious adverse events (SAEs)
All stages (except Stage 1/Step 1)
Time frame: From baseline to the end of the study (up to 6 years, 5 months)
Incidence, severity and nature of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs)
All stages (except Stage 1/Step 1)
Time frame: From baseline to the end of the study (up to 6 years, 5 months)
Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs
All stages (except Stage 1/Step 1). Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator.
Time frame: From baseline to the end of the study (6 years, 5 months)
Time between two consecutive injections
Stage 1/Step 3 .
Time frame: From baseline to the end of the study (up to 6 years, 5 months)
Percentage of participants with binding antibodies to IPN10200
Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3
Time frame: At Week 4 , Week 24 and Week 36
Percentage of participants with neutralising antibodies to IPN10200
Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3
Time frame: At Week 4 , Week 24 and Week 36
Percentage of participants with binding antibodies to BontA
Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3
Time frame: At Week 4 , Week 24 and Week 36
Percentage of participants with neutralising antibodies to BontA
Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3
Time frame: At Week 4 , Week 24 and Week 36