Head-to-Head Comparison of All Botulinum Neurotoxin Type A Products for Glabellar Rhytides

NCT06448676 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2024-514936-26-00
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study Type: This is a multicenter, triple-blind, randomized controlled trial. Purpose: The goal of this clinical trial is to compare the effectiveness and safety of all five commercially available Botulinum Neurotoxin Type A (BoNT-A) products for treating glabellar rhytides, commonly known as frown lines. This study is designed to provide comprehensive data on how these treatments compare in terms of improving frown lines and the duration of their effects. Main Questions the Study Aims to Answer: Which BoNT-A product provides the longest lasting effect on reducing glabellar rhytides? How do these products compare in terms of safety and the occurrence of side effects? Participant Tasks: Women aged 18 years or older with moderate to severe glabellar lines will participate. Participants will receive injections of a BoNT-A product into specific facial muscles. They will need to take weekly photographs using their smartphones to document changes in their frown lines. These photos will be securely sent to our research team for analysis. Participants will complete questionnaires at the start and end of the study to assess their satisfaction, quality of life, and any changes in their condition. Comparison Group: Researchers will compare participants receiving different types of BoNT-A products to see which one is more effective at reducing frown lines and maintaining these effects over time. The safety profiles of these products will also be compared to determine which has the fewest and least severe side effects. This study aims to fill important gaps in our understanding of Botulinum Neurotoxin Type A treatments, guiding more effective clinical decisions and improving patient outcomes.

Conditions

Wrinkle

Outcome Measures

Primary Outcomes (1)

• Duration of Clinical Efficacy

  Period until loss of treatment effect, measured as the percentage of participants who maintain at least a 1-point improvement in glabellar line severity at maximum frown from baseline to week 16, assessed using the "four-point clinical severity score for glabellar frown lines" developed by Honeck.

  From baseline to week 16

Secondary Outcomes (10)

• Duration of Clinical Efficacy

  Kaplan-Meier survival curves and Cox proportional hazards models to analyze the time to complete loss of effect across the entire study duration (From baseline to week 30)

• Incidence of Adverse Events (AEs)

  From baseline to week 16

• Quality of Life (FACE-Q)

  From baseline to week 16

• Social Functioning (FACE-Q)

  From baseline to week 16

• Satisfaction with the Result (FACE-Q)

  From baseline to week 16

Study Arms (7)

OnabotulinumtoxinA: 20 units

ACTIVE COMPARATOR

20 units (4-4-4-4-4) Commercial Name: Botox® Producing Company: Allergan, an AbbVie company Location: Dublin, Ireland Additional Commercial Names: Vistabel® (in some regions, especially Europe)

Drug: Botulinum toxin type A

IncobotulinumtoxinA: 20 units

ACTIVE COMPARATOR

20 units (4-4-4-4-4) Commercial Name: Xeomin® Producing Company: Merz Pharmaceuticals Location: Frankfurt, Germany Additional Commercial Names: Bocouture® (for aesthetic use in some regions)

Drug: Botulinum toxin type A

AbobotulinumtoxinA: 50 (Speywood) units

ACTIVE COMPARATOR

50 units (10-10-10-10-10) Commercial Name: Dysport® Producing Company: Ipsen Biopharmaceuticals, Inc. Location: Paris, France Additional Commercial Names: Azzalure® (for aesthetic use in some regions)

Drug: Botulinum toxin type A

AbobotulinumtoxinA: 60 (Speywood) units

ACTIVE COMPARATOR

60 units (12-12-12-12-12) Commercial Name: Dysport® Producing Company: Ipsen Biopharmaceuticals, Inc. Location: Paris, France Additional Commercial Names: Azzalure® (for aesthetic use in some regions)

Drug: Botulinum toxin type A

PrabotulinumtoxinA 20 units

ACTIVE COMPARATOR

20 units (4-4-4-4-4) Commercial Name: Jeuveau® Producing Company: Evolus, Inc. Location: Newport Beach, California, USA Additional Commercial Names: Nuceiva® (for aesthetic use in some regions)

Drug: Botulinum toxin type A

Excluded: DaxibotulinumtoxinA 20 units (reason for exclusion: not available in the EU)

ACTIVE COMPARATOR

20 units (4-4-4-4-4) Commercial Name: Daxxify® Producing Company: Revance Therapeutics, Inc. Location: Nashville, Tennessee, USA

Drug: Botulinum toxin type A

Excluded: LetibotulinumtoxinA-wlbg: 20 units (reason for exclusion: not available in the EU).

ACTIVE COMPARATOR

Arm Description: 20 units (4-4-4-4-4) Commercial Name: Letybo® Producing Company: Hugel Inc. Location: Chuncheon-si, South Korea

Drug: Botulinum toxin type A

Interventions

Botulinum toxin type A DRUG

Head-to-head comparison of all commercially available botulinum neurotoxin type A products

AbobotulinumtoxinA: 50 (Speywood) units; AbobotulinumtoxinA: 60 (Speywood) units; Excluded: DaxibotulinumtoxinA 20 units (reason for exclusion: not available in the EU); Excluded: LetibotulinumtoxinA-wlbg: 20 units (reason for exclusion: not available in the EU).; IncobotulinumtoxinA: 20 units; OnabotulinumtoxinA: 20 units; PrabotulinumtoxinA 20 units

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged 18 years or over, with moderate to severe glabellar lines
• Willing to provide written informed consent
• American Society of Anesthesiologists (ASA) Physical Status Classification 1 or 2

You may not qualify if:

• ASA Classification 3 or over
• History of hypersensitivity or adverse reactions to botulinum toxin or any of its components
• Infection at the injection site
• Previous treatment with botulinum toxin (lifetime)
• Pregnant or breastfeeding women
• Neuromuscular disorders or conditions that could interfere with the study assessments

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Universitair Medical Centrum Groningen: collaborator

Related Publications (19)

• Decates T, de Wijs L, Nijsten T, Velthuis P. Numbers on injectable treatments in the Netherlands in 2016. J Eur Acad Dermatol Venereol. 2018 Aug;32(8):e328-e330. doi: 10.1111/jdv.14877. Epub 2018 Mar 6. No abstract available.

  PMID: 29444367 BACKGROUND

• Decates TS, Velthuis P, Zarringam D, Bruin L, Schepers RH, van der Lei B. Upward trend in number of injectable treatments in the Netherlands 2016-2019. J Cosmet Dermatol. 2021 Sep;20(9):3049-3051. doi: 10.1111/jocd.14339. Epub 2021 Jul 19. No abstract available.

  PMID: 34403196 BACKGROUND

• Steenen SA, Bauland CG, de Lange J, van der Lei B. Complications After Botulinum Neurotoxin Type A and Dermal Filler Injections: Data From a Large Retrospective Cohort Study. Aesthet Surg J. 2023 Jan 9;43(1):NP56-NP63. doi: 10.1093/asj/sjac228. No abstract available.

  PMID: 35953448 BACKGROUND

• Jia Z, Lu H, Yang X, Jin X, Wu R, Zhao J, Chen L, Qi Z. Adverse Events of Botulinum Toxin Type A in Facial Rejuvenation: A Systematic Review and Meta-Analysis. Aesthetic Plast Surg. 2016 Oct;40(5):769-77. doi: 10.1007/s00266-016-0682-1. Epub 2016 Aug 5.

  PMID: 27495260 BACKGROUND

• Zargaran D, Zoller FE, Zargaran A, Mosahebi A. Complications of facial cosmetic botulinum toxin A injection: analysis of the UK Medicines & Healthcare Products Regulatory Agency registry and literature review. J Plast Reconstr Aesthet Surg. 2022 Jan;75(1):392-401. doi: 10.1016/j.bjps.2021.05.074. Epub 2021 Jun 17.

  PMID: 34456155 BACKGROUND

• Gostimir M, Liou V, Yoon MK. Safety of Botulinum Toxin A Injections for Facial Rejuvenation: A Meta-Analysis of 9,669 Patients. Ophthalmic Plast Reconstr Surg. 2023 Jan-Feb 01;39(1):13-25. doi: 10.1097/IOP.0000000000002169. Epub 2022 Mar 30.

  PMID: 35353777 BACKGROUND

• Zargaran D, Zoller F, Zargaran A, Rahman E, Woollard A, Weyrich T, Mosahebi A. Complications of Cosmetic Botulinum Toxin A Injections to the Upper Face: A Systematic Review and Meta-Analysis. Aesthet Surg J. 2022 Apr 12;42(5):NP327-NP336. doi: 10.1093/asj/sjac036.

  PMID: 35178552 BACKGROUND

• Li X, Sui C, Xia X, Chen X. Efficacy and Safety of Botulinum Toxin Type A for Treatment of Glabellar Lines: A Network Meta-Analysis of Randomized Controlled Trials. Aesthetic Plast Surg. 2023 Feb;47(1):365-377. doi: 10.1007/s00266-022-03018-y. Epub 2022 Sep 12.

  PMID: 36097079 BACKGROUND

• Kerscher M, Fabi S, Fischer T, Gold M, Joseph J, Prager W, Rzany B, Yoelin S, Roll S, Klein G, Maas C. IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines. J Drugs Dermatol. 2021 Oct 1;20(10):1052-1060. doi: 10.36849/JDD.6377.

  PMID: 34636520 BACKGROUND

• Polacco MA, Singleton AE, Barnes CH, Maas C, Maas CS. A Double-Blind, Randomized Clinical Trial to Determine Effects of Increasing Doses and Dose-Response Relationship of IncobotulinumtoxinA in the Treatment of Glabellar Rhytids. Aesthet Surg J. 2021 May 18;41(6):NP500-NP511. doi: 10.1093/asj/sjaa220.

  PMID: 32722793 BACKGROUND

• Joseph J, Moradi A, Lorenc ZP, Coleman K, Ablon G, Kaufman-Janette J, Cox SE, Campbell A, Dayan S, Berg AK, Munavalli G. AbobotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines: A Randomized, Dose-Escalating, Double-Blind Study. J Drugs Dermatol. 2021 Sep 1;20(9):980-987. doi: 10.36849/jdd.6263.

  PMID: 34491016 BACKGROUND

• Lorenc ZP, Adelglass JM, Avelar RL, Baumann L, Beer KR, Cohen JL, Cox SE, Dayan SH, Dover JS, Downie JB, Draelos ZD, Goldman MP, Gross JE, Joseph JH, Kaufman-Janette J, Moy RL, Nestor M, Schlessinger J, Smith SR, Weiss RA. The Second of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients. Aesthet Surg J. 2021 Nov 12;41(12):1423-1438. doi: 10.1093/asj/sjaa382.

  PMID: 33944913 BACKGROUND

• Taylor SC, Grimes PE, Joseph JH, Jonker A, Avelar RL. PrabotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines in Adult Patients With Skin of Color: Post Hoc Analyses of the US Phase III Clinical Study Data. Dermatol Surg. 2021 Apr 1;47(4):516-521. doi: 10.1097/DSS.0000000000002864.

  PMID: 33165078 BACKGROUND

• Dayan S, Joseph J, Moradi A, Lorenc ZP, Coleman K, Ablon G, Kaufman-Janette J, Cox SE, Campbell A, Munavalli G, Prygova I. Subject satisfaction and psychological well-being with escalating abobotulinumtoxinA injection dose for the treatment of moderate to severe glabellar lines. J Cosmet Dermatol. 2022 Jun;21(6):2407-2416. doi: 10.1111/jocd.14906. Epub 2022 Apr 12.

  PMID: 35266281 BACKGROUND

• Bertucci V, Solish N, Kaufman-Janette J, Yoelin S, Shamban A, Schlessinger J, Snyder D, Gallagher C, Liu Y, Shears G, Rubio RG. DaxibotulinumtoxinA for Injection has a prolonged duration of response in the treatment of glabellar lines: Pooled data from two multicenter, randomized, double-blind, placebo-controlled, phase 3 studies (SAKURA 1 and SAKURA 2). J Am Acad Dermatol. 2020 Apr;82(4):838-845. doi: 10.1016/j.jaad.2019.06.1313. Epub 2019 Nov 29.

  PMID: 31791824 BACKGROUND

• Steenen SA, Bauland CG, van der Lei B, Su N, van Engelen MDG, Anandbahadoer-Sitaldin RDRRAL, Koeiman W, Jawidan T, Hamraz Y, Lange J. Head-to-head comparison of 4 hyaluronic acid dermal fillers for lip augmentation: A multicenter randomized, quadruple-blind, controlled clinical trial. J Am Acad Dermatol. 2023 Apr;88(4):932-935. doi: 10.1016/j.jaad.2022.11.012. Epub 2022 Nov 9. No abstract available.

  PMID: 36370906 BACKGROUND

• Shome D, Kapoor R, Khare S. Two different types of botulinum toxins: Is there a difference in efficacy and longevity? J Cosmet Dermatol. 2019 Dec;18(6):1635-1641. doi: 10.1111/jocd.12949. Epub 2019 May 28.

  PMID: 31135088 BACKGROUND

• Bohart Z, Dashtipour K, Kim H, Schwartz M, Zuzek A, Singh R, Nelson M. Real-world differences in dosing and clinical utilization of OnabotulinumtoxinA and AbobotulinumtoxinA in the treatment of upper limb spasticity. Toxicon. 2024 Apr;241:107678. doi: 10.1016/j.toxicon.2024.107678. Epub 2024 Mar 4.

  PMID: 38447766 BACKGROUND

• Honeck P, Weiss C, Sterry W, Rzany B; Gladys study group. Reproducibility of a four-point clinical severity score for glabellar frown lines. Br J Dermatol. 2003 Aug;149(2):306-10. doi: 10.1046/j.1365-2133.2003.05436.x.

  PMID: 12932236 BACKGROUND

MeSH Terms

Interventions

Botulinum Toxins, Type A

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Jan de Lange, MD DMD PhD

  Amsterdam University Medical Centers

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Serge A. Steenen, MD DMD

CONTACT

+316 26 457 415; s.a.steenen@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Trial participants, data collectors, the statistician, and outcome assessors were blinded to the study-group assignments. Blinded syringes are labeled a sticker containing no information other than the allocated study number. After reconstitution, syringes were stored under hygienic non-sterile conditions between 39-46F in medical refrigerators. The safety related to this sterile transfer is substantiated by several studies.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. Jan de Lange, MD DMD

Model Details: This study is a triple-blind, multi-center, parallel-group randomized controlled trial designed to compare the efficacy and safety of onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, prabotulinumtoxinA, and daxibotulinumtoxinA, for the treatment of glabellar rhytides.

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 7, 2024
• Study Start: January 1, 2025
• Primary Completion: October 1, 2025
• Study Completion: November 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09