A study to assess the safety and efficacy of IPN10200 in adult participants with moderate to severe upper facial lines

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ipsen Innovation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Physical Phenomena [G01]

Trial duration

20 Mar 2024 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ipsen Innovation

External identifiers

EU CT number

2024-512782-14-00

EudraCT number

2020-003746-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Dose response, Efficacy

1. To assess the safety and tolerability of increasing doses of a single treatment of IPN10200 compared with placebo in participants with moderate to severe GL.

2. To assess the safety and efficacy of IPN10200 compared with placebo in improving the appearance of moderate to severe lines (GL,FHL, LCL) as measured by the Investigator's Live Assessment (ILA) and Subject's Self-assessment (SSA) at maximum contraction at Week 4.

Secondary objectives 8

1. 1. To assess the efficacy of IPN10200 compared with placebo in improving the appearance of moderate to severe upper facial lines (GL, FHL and LCL) measured by the ILA and SSA at maximum contraction at Week 4
2. 2. To assess: a. 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 as measured by the ILA at rest and maximum contraction, and by the participant as measured by the SSA at maximum contraction and Subject's Level of Satisfaction. b. time to onset of treatment response c. safety d. the presence of IPN10200 antibodies. e. satisfaction with facial appearance
3. 3. To determine the duration of treatment response based on ILA and SSA at maximum contraction
4. 4. To assess 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
5. 5. Open-label Phase: To assess the safety and tolerability of IPN10200 following repeat doses in improving the appearance of moderate to severe GL
6. 6. Open-label Phase: To assess the efficacy profiles of repeat doses of IPN10200 in improving of the appearance of moderate to severe GL at each timepoint assessed: - Assessed by the investigator as measured by the ILA at rest and maximum contraction - Assessed by the participant as measured by: • SSA at maximum contraction • Subject’s Level of Satisfaction
7. 7. Open-label Phase: To assess the time of retreatment
8. 8. Open-label Phase: To assess the presence of IPN10200 antibodies

Conditions and MedDRA coding

Treatment of Moderate to Severe Upper Facial Lines

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU. Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
2. 2. 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.
3. 3. 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.
4. 4. 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).
5. 5. 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).
6. 6. 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.
7. 7. 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.
8. 8. Dissatisfied or very dissatisfied (Grade 2 or 3) with their lines (Stages 1 to 3) at Baseline, as assessed by the SLS.
9. 9. 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.
10. 10. Capable of giving signed informed consent includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
11. 11. Participant has both the time and the ability to complete the study and comply with study instructions.
12. 12. Does not reside in an institution by administrative or court order.
13. 13. 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 21

1. 1. 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).
2. 2. A history of eyelid blepharoplasty or brow lift within the past 5 years
3. 3. A history of facial nerve palsy.
4. 4. Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin.
5. 5. 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.)
6. 6. 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)
7. 7. 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.
8. 8. Any prior treatment with permanent fillers in the upper face including the GL, FHL and LCL area.
9. 9. 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.
10. 10. Any planned facial cosmetic surgery during the study.
11. 11. 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.
12. 12. 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.
13. 13. 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.
14. 14. Known positive for hepatitis B antigen, or hepatitis C virus antibody, or for human immunodeficiency virus (HIV) or a diagnosis of acquired immunodeficiency syndrome.
15. 15. 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
16. 16. An inability to substantially lessen GL and/or horizontal forehead rhytids even by physically spreading them apart as determined by the investigator.
17. 17. Known allergy or hypersensitivity to BoNT, or any excipients of IPN10200 or Dysport/Azzalure, or allergy to cow's milk protein.
18. 18. A history of drug or alcohol abuse.
19. 19. Pregnant women, nursing women, premenopausal women or women of childbearing potential not willing to practice a highly effective form of contraception method.
20. 20. 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.
21. 21. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 13

1. 1. Incidence of treatment emergent adverse events (TEAEs) at each dose At Stage 1/Step 1, Stage 3
2. 2. Incidence of serious adverse events (SAEs) at each dose At Stage 1/Step 1, Stage 3
3. 3. Incidence of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs) At Stage 1/Step 1, Stage 3
4. 4. 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:
5. 4. 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)s at maximum frown and at rest where 0 is “none” and 3 is “severe”
6. 4. 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: 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”
7. 5. 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”
8. 5. 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: 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”
9. 6. 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”
10. 6. 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: 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”
11. 7. 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.
12. 8. Percentage of participants with clinically significant Change from baseline in 12-lead Electrocardiogram (ECG) readings Double Blind phase.
13. 9. 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.

Secondary endpoints 23

1. 1. 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)
2. 1. 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”
3. 1. 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) 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”
4. 2. 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.
5. 3. Percentage of pa rticipants with clinically significant change from baseline in facial and focused neurological/physical examination. Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator.
6. 4. Percentage of participants response to treatment as achieved by a score of “none” or “mild” as measured by the ILA at rest For all stages.
7. 5. 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
8. 6. 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. S
9. 7. Percentage of participants response to treatment as achieved by a score of “very satisfied” or “satisfied” on the Subject Level of Satisfaction (SLS) for each concerned facial area. For all stages
10. 8. Duration of treatment response based on ILA and SSA at maximum contraction for each concerned facial area. For all stages
11. 9. 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.
12. 10. Satisfaction with facial appearance, measured by Facial Appearance Overall scale score on the Face-Q satisfaction scale. Stage 3.
13. 10. 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).
14. 11. 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.
15. 12. Incidence, severity and nature of treatment emergent adverse events (TEAEs). All stages (except Stage 1/Step 1)
16. 13. Incidence, severity and nature of serious adverse events (SAEs) All stages (except Stage 1/Step 1)
17. 14. 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)
18. 15. 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
19. 16. Time between two consecutive injections. Stage 1/Step 3
20. 17. Percentage of participants with binding antibodies to IPN10200 Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3
21. 18. Percentage of participants with neutralising antibodies to IPN10200 Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3
22. 19. Percentage of participants with binding antibodies to BontA Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3
23. 20. Percentage of participants with neutralising antibodies to BontA Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ipsen Innovation

Sponsor organisation

Ipsen Innovation

Address

70 Rue Balard

City

Paris

Postcode

75015

Country

France

Scientific contact point

Organisation

Ipsen Innovation

Contact name

Neurosciences Therapeutic Area, R&D

Public contact point

Organisation

Ipsen Innovation

Contact name

Neurosciences Therapeutic Area, R&D

Third parties 5

Locations

2 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications