A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring
Background:. Connective tissue growth factor (CTGF) is a matricellular protein that plays a key role in wound healing and scar formation. Inhibition of CTGF by a specific antisense oligonucleotide significantly reduced scarring and fibrosis in animal models. This study examined whether an antisense...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2018-09-01
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| Series: | Plastic and Reconstructive Surgery, Global Open |
| Online Access: | http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000001861 |
| _version_ | 1830285984762167296 |
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| author | Jeremy D. Gale, PhD Jeff Jensen, BS Gabe Berman, BA William Freimuth, MD Gang Li, PhD Andreas Pleil, PhD Malik Kutty, MD Andrew Rosenthal, MD C.B. Boswell, MD V., E. Magnus Noah, Dr. Med Leroy Young, MD |
| author_facet | Jeremy D. Gale, PhD Jeff Jensen, BS Gabe Berman, BA William Freimuth, MD Gang Li, PhD Andreas Pleil, PhD Malik Kutty, MD Andrew Rosenthal, MD C.B. Boswell, MD V., E. Magnus Noah, Dr. Med Leroy Young, MD |
| author_sort | Jeremy D. Gale, PhD |
| collection | DOAJ |
| description | Background:. Connective tissue growth factor (CTGF) is a matricellular protein that plays a key role in wound healing and scar formation. Inhibition of CTGF by a specific antisense oligonucleotide significantly reduced scarring and fibrosis in animal models. This study examined whether an antisense oligonucleotide that inhibits human CTGF expression could reduce the severity of hypertrophic scar formation in patients following surgical revision of preexisting breast scars.
Methods:. This study was a 24-week multicenter, randomized, double-blind, within-subject, placebo-controlled phase 2b study evaluating the efficacy and safety of PF-06473871 in 2 regimens of either 3 or 4 intradermal injections (postsurgery weeks 2, 5, 8, and 11) of 5 mg/cm adjacent to the new surgical incision. One hundred subjects with bilateral hypertrophic scars resulting from prior breast surgery were randomized. Efficacy was determined by the Patient and Observer Scar Assessment Scale (POSAS).
Results:. The Physician/Observer POSAS overall opinion score at (week 24) for the 4-injection regimen demonstrated a statistically significant (P = 0.022) treatment difference from placebo of 0.68, and the treatment difference for the 3-injection regimen was nonsignificant (P = 0.4). Physician evaluation of scar severity at (week 24) with the photo-guide in the 4-injection regimen had a significant reduction (point estimate of treatment difference of 0.43 favoring PF-06473871). The surgical effect was approximately 2.0 at week 24 and was nearly 3 times greater than the treatment effect. Patient evaluations using the POSAS and photo-guide were not significantly improved with either dose regimen. PF-06473871 was generally well tolerated systemically and locally.
Conclusion:. The 4-dose regimen of PF-06473871 provided statistically significant improvement, inhibiting severity of hypertrophic scar formation based on physician assessment. However, the effect of revision surgery alone is significant and may dominate the treatment effect of PF-06473871. |
| first_indexed | 2024-12-19T03:50:48Z |
| format | Article |
| id | doaj.art-842b32a03d4048a695483ad7a0dbf52e |
| institution | Directory Open Access Journal |
| issn | 2169-7574 |
| language | English |
| last_indexed | 2024-12-19T03:50:48Z |
| publishDate | 2018-09-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Plastic and Reconstructive Surgery, Global Open |
| spelling | doaj.art-842b32a03d4048a695483ad7a0dbf52e2022-12-21T20:37:00ZengWolters KluwerPlastic and Reconstructive Surgery, Global Open2169-75742018-09-0169e186110.1097/GOX.0000000000001861201809000-00017A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin ScarringJeremy D. Gale, PhD0Jeff Jensen, BS1Gabe Berman, BA2William Freimuth, MD3Gang Li, PhD4Andreas Pleil, PhD5Malik Kutty, MD6Andrew Rosenthal, MD7C.B. Boswell, MD8V., E. Magnus Noah, Dr. Med9Leroy Young, MD10From the *Pfizer Inc., Cambridge, Mass.†Pfizer Inc., San Diego, Calif.†Pfizer Inc., San Diego, Calif.From the *Pfizer Inc., Cambridge, Mass.‡Pfizer Inc., Collegeville, Pa.†Pfizer Inc., San Diego, Calif.§Luxe Plastic Surgery, Sugarland, Tex.¶Altus Research, Lake Worth, Fla.‖Body Aesthetic Plastic Surgery, St. Louis, Mo.**Klinik fur Plastische, Rekonstruktive and Asthetische Chirurgie, Handchirurgie am Roten Kreuz Kranke, Hansteinstrasse 29, Kassel, Hessen, Germany††Mercy Health Research, Washington, Mo.Background:. Connective tissue growth factor (CTGF) is a matricellular protein that plays a key role in wound healing and scar formation. Inhibition of CTGF by a specific antisense oligonucleotide significantly reduced scarring and fibrosis in animal models. This study examined whether an antisense oligonucleotide that inhibits human CTGF expression could reduce the severity of hypertrophic scar formation in patients following surgical revision of preexisting breast scars. Methods:. This study was a 24-week multicenter, randomized, double-blind, within-subject, placebo-controlled phase 2b study evaluating the efficacy and safety of PF-06473871 in 2 regimens of either 3 or 4 intradermal injections (postsurgery weeks 2, 5, 8, and 11) of 5 mg/cm adjacent to the new surgical incision. One hundred subjects with bilateral hypertrophic scars resulting from prior breast surgery were randomized. Efficacy was determined by the Patient and Observer Scar Assessment Scale (POSAS). Results:. The Physician/Observer POSAS overall opinion score at (week 24) for the 4-injection regimen demonstrated a statistically significant (P = 0.022) treatment difference from placebo of 0.68, and the treatment difference for the 3-injection regimen was nonsignificant (P = 0.4). Physician evaluation of scar severity at (week 24) with the photo-guide in the 4-injection regimen had a significant reduction (point estimate of treatment difference of 0.43 favoring PF-06473871). The surgical effect was approximately 2.0 at week 24 and was nearly 3 times greater than the treatment effect. Patient evaluations using the POSAS and photo-guide were not significantly improved with either dose regimen. PF-06473871 was generally well tolerated systemically and locally. Conclusion:. The 4-dose regimen of PF-06473871 provided statistically significant improvement, inhibiting severity of hypertrophic scar formation based on physician assessment. However, the effect of revision surgery alone is significant and may dominate the treatment effect of PF-06473871.http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000001861 |
| spellingShingle | Jeremy D. Gale, PhD Jeff Jensen, BS Gabe Berman, BA William Freimuth, MD Gang Li, PhD Andreas Pleil, PhD Malik Kutty, MD Andrew Rosenthal, MD C.B. Boswell, MD V., E. Magnus Noah, Dr. Med Leroy Young, MD A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring Plastic and Reconstructive Surgery, Global Open |
| title | A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring |
| title_full | A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring |
| title_fullStr | A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring |
| title_full_unstemmed | A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring |
| title_short | A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring |
| title_sort | placebo controlled study of pf 06473871 anti connective tissue growth factor antisense oligonucleotide in reducing hypertrophic skin scarring |
| url | http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000001861 |
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