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Report for Clinical Trial NCT00716014

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Single-Center, Placebo-Controlled, Rising Dose to Tolerance and Safety Study of TD101, an siRNA Designed for Treatment of Pachyonychia Congenita

Pachyonychia congenita (PC) is a rare, autosomal dominant keratin disorder affecting the nails, skin, oral mucosae, larynx, hair and teeth. Pathogenic mutations in keratin K6a, K6b, K16 or K17 act via a dominant negative mechanism, leading to manifestations of the disease. The most disabling PC symptom is a painful plantar blistering and keratoderma that requires use of ambulation devices in more than 50 percent of patients. Despite our understanding of the molecular basis of PC, current treatment is limited to mechanical removal of the thick calluses, non-specific topical keratolytics, and oral retinoids, none of which alleviates blistering or plantar pain satisfactorily. A public charity, PC Project, has been founded to support the development of treatments for PC (www.pachyonychia.org). In collaboration with this charity, a small company, TransDerm, Inc., has developed a small interfering RNA (siRNA) that specifically targets a mutation in one of the PC keratins, K6a. As this siRNA targets a single nucleotide mutation, it will only be effective against PC subjects harboring this specific mutation. There are currently only six known patients who carry this mutation in the International Pachyonychia Congenita Research Registry, but three of these patients live in Salt Lake City (a mother and two of her children). We propose to perform a Phase Ib clinical trial to test the safety and tolerability of TD101 in PC patients carrying an N171K mutation. We will complete treatment of the adult patient prior to recruitment of the minors.

NCT00716014 Pachyonychia Congenita
MeSH:Pachyonychia Congenita Nails, Malformed
HPO:Abnormality of the nail

2 Interventions

Name: TD101

Description: TD101 is injection into a callus on the bottom of one of the patient's feet
Type: Drug
Group Labels: 1

Foot 1

Name: Normal saline (placebo)

Description: A normal saline solution (placebo) is injected into one of the patient's feet.
Type: Drug
Group Labels: 1

Foot 2


Primary Outcomes

Measure: Determine safety/toxicity of TD101

Time: 18 weeks, followed by 3-month wash out period

Secondary Outcomes

Measure: Determine efficacy of TD101

Time: 18 weeks, followed by 3-month wash out period

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 N171K

We propose to perform a Phase Ib clinical trial to test the safety and tolerability of TD101 in PC patients carrying an N171K mutation. --- N171K ---

Inclusion Criteria: - A positive genetic identification of the N171K mutation in the keratin 6a gene from a CLIA certified laboratory; - Witnessed, signed informed consent approved by Institutional Review Board/Ethics Committee; - A signed Health Information Portability and Accountability Act (HIPAA) authorization form which permits the use and disclosure of patient's individually identifiable health information for those enrolled in the United States of America; - Male or female subjects of any race 10 years of age and older; - Complete physical examination and medical history indicating no abnormalities that will interfere with study objectives; - Normal or not clinically significant baseline laboratory tests, including hemogram, ANA, serum chemistry panel, urinalysis, C3a, Bb, and APTT,PT; - Negative pregnancy test (females only). --- N171K ---



HPO Nodes


HPO:
HP:0001597: Abnormality of the nail
Genes 667
IFT52 IHH WHCR TP63 CTC1 TREX1 KRT17 ALOX12B POLR3A PORCN GPC4 SOX11 OFD1 IL17RC COL2A1 KCTD1 KRT86 FOXN1 CPT2 TCTN3 GPR101 NECTIN1 KRT6B TNFRSF1B MAP2K2 GPC4 ARX KRT14 BCR HYMAI KRT14 KDF1 EVC2 DOCK6 RBPJ CLEC7A KRT86 PITX1 CTBP1 NOTCH1 DPM1 TP63 FLT4 PLEC LAMC2 KRT5 TINF2 FOXP3 DPF2 TP63 GDF5 ORC1 ZMPSTE24 JUP TINF2 ZBTB20 ATP2A2 CDH1 SOX18 RECQL4 MAP2K1 RIPK4 DPH1 CYB5R3 WNK1 GPC4 SMARCAD1 RUNX2 TINF2 IL17RA RNU4ATAC NHP2 CTSC ITGB4 TERT KCTD1 WNT10A DOCK6 CTSK ZSWIM6 SETBP1 GRHL2 ATP6V1B2 SMARCA4 NEUROD2 SETD2 AKT1 EVC KRAS NIPAL4 KCNH1 KLHL24 TP63 EVC2 CERS3 HEPHL1 COL11A1 WDR35 GNAO1 NHP2 ARID2 SHOC2 FGFRL1 MBTPS2 VEGFC TGM1 KDM1A HGD TNFRSF1B COL7A1 CARD14 PLCD1 PGAP3 RECQL4 ANAPC1 LMNA EVC STAMBP NOG CKAP2L NOP10 NDUFB11 COL7A1 KRT81 HRAS FLNA NLRP1 PTDSS1 IFNG KRT1 TRIM8 UBE2A LMX1B MAF MBTPS2 COX7B NSD1 LAMB3 COL7A1 KIF22 WNT7A WNT5A NHP2 PIGN NSD1 NTRK1 TP63 SOX4 PTEN DSG4 FZD2 COL7A1 TSC1 KRT17 STAT3 ABCA1 COL7A1 INSR CYB5A KRT6B SLURP1 TSC1 PORCN PIGQ RAB3GAP2 CAST ARID1A EED KRT16 FOXN1 KRT16 EVC UMPS ATL1 TRRAP SLCO2A1 GJA1 SMARCB1 ACVRL1 RTEL1 KCNH1 GJC2 DSP PLCD1 TERT BMP2 FERMT1 COL7A1 IFT122 LAMA3 KRT5 WDR73 TRAF6 KRT5 EZH2 STXBP1 WRAP53 ATP6V1B2 LMNA DLX5 KRT1 STK11 FGFR2 GJA1 SHOX ACD EXT2 RPS6KA3 ABCA12 EDARADD GJA1 CWC27 B3GALT6 LAMB3 LIPN NFKB2 NFKB2 POC1A DLX3 IFT43 HFE CCDC22 RNF113A INSR SULT2B1 PIGY DST LPAR6 LRP4 NPR2 DSP PARN SMARCE1 STIM1 DVL3 STXBP1 FIG4 ATP6V1B2 KIF15 ITGB4 GLI1 KRT1 DVL3 SLURP1 ELN COL7A1 TP63 COL7A1 TFAP2A ITGA6 ABCA1 UROD TINF2 DKC1 WNT5A ACTG2 DSP ZMPSTE24 GPC3 PIGP WNT10A KRT74 ERCC2 COL11A2 IL36RN FGFR2 GJB6 HPGD TELO2 ELN LAMC2 CASK RPS6KA3 DNAJC21 EFNB1 KRT16 LAMA3 MACROH2A1 SRY SMARCE1 LMX1B GPC4 COL7A1 DYNC2LI1 EVC2 ALOX12B DYNC2LI1 SLC35D1 AP1B1 IRF6 PKP1 ERCC2 GJB4 EVC2 PEPD NSDHL COL7A1 SMARCC2 WASHC5 EDAR PIGA WRAP53 GLI3 KCNH1 NOG WNT10A STING1 COL7A1 STXBP1 ACAN ARHGAP31 ROR2 RFC2 MAPK1 COL17A1 ERCC3 ATP2A2 TERC KRT5 CTLA4 DKC1 NSUN2 ABCA12 RSPO1 LMNA GJB2 DVL1 EOGT PRKD1 DVL1 ALOXE3 RIPK4 ITGA6 COL17A1 RETREG1 IFIH1 LAMB3 SOST SLC25A22 COL7A1 KIF1A ENG GJA1 GNA11 TERT KCNA1 DLL4 ARID1A TP63 PQBP1 MBTPS2 KRT83 TRAF3IP2 CARD14 KRT83 SOX11 CDKL5 WDR35 RSPO4 SOST EDARADD GDF5 EFNB1 CTSK PNPLA1 LAMA3 INSR WNK1 BRAF TP63 TAT ARID1B LAMC2 ABCA12 GLI3 PPM1D LIMK1 EDARADD NECTIN4 TBL2 LAMB3 COL7A1 SDR9C7 SHANK3 ZMPSTE24 PERP PEX1 LRP4 KIF1A ZBTB20 MPLKIP TAF1 SCN2A LMNA SLC39A4 GJB3 ATR HLA-C IKBKG JUP RIPK4 HUWE1 FLNB PEX1 MMP1 GSN WNT7A ALG3 KIF11 COL14A1 FUCA1 PLEC UBE2A PIGW RETREG1 APC COL7A1 CASR WNT7A AFF4 NSD2 TRPS1 LIG4 POP1 TERC SF3B1 KCNH1 SHANK3 PEX6 DPF2 FGFR1 TBC1D24 CLIP2 FLT4 KRT9 BMPR1B KDF1 RAB3GAP1 PIGO ANTXR1 DLX3 WDR19 SIK1 ACD COL7A1 CTSC CD28 BMPER EVC NOTCH2 CTLA4 LORICRIN DSP NOTCH1 AP1S3 VEGFC RLIM MBTPS2 GTF2E2 DSG1 PARN RAB3GAP2 BHLHA9 HOXA13 ITGB4 TBC1D24 SLC25A24 IL11RA MSX1 KDSR KANK2 TGM1 KRT14 CD28 MECP2 KRT14 MBTPS2 NOTCH2 USB1 TSC2 IHH TP63 PLEC KRT14 LMX1B FOXC2 ITGA3 PEX7 ADNP CDSN NTNG1 KRT6A ROR2 CD151 KRT5 ADAMTSL2 GTF2H5 TARS1 KRT6A RTEL1 CAMK2G KRT81 SCN1B PIGV ARHGAP31 BMP4 NOG ECE1 PEX6 CYP4F22 TINF2 GJB2 GJB2 PLEC LAMC2 ALOXE3 ZSWIM6 RIPK4 COL11A1 MCTP2 UBR1 GJB6 MPLKIP ALOX12B TSC2 RTEL1 PIGN NXN NOG PIGV TSC2 DSG1 NIPAL4 AIP COL7A1 LETM1 NECTIN1 DLL4 GJB2 TRPS1 EZH2 GJA1 GTF2I SLC39A4 PRKAR1A SMARCD2 ATP6V0A2 ROR2 PPP1CB PIGL PLOD3 INPPL1 C15ORF41 RNU4ATAC POLR3A SCN9A KRT14 CDKL5 GDF5 FTO ARID1B APC2 LMNA EDAR NPM1 KRT14 SCN9A KCNN3 TGM1 DKC1 LAMC2 NSD1 PPP2R5D GJB6 EOGT KRT5 POMP TFAP2A HCCS SRCAP FLNB CSTA FAM111B KRT5 TRPV3 MLXIPL HRAS SMARCAD1 TBX3 PGAP2 PDE4D IFT122 TET2 GJB2 MMP1 CSTB TGM1 IKBKG EDAR IRF6 COL17A1 FIG4 MSX1 EBP IL17F AAGAB BAZ1B FHL1 HOXC13 TBX4 FERMT1 ALOXE3 KRT85 ATP2A2 LRP4 DPH1 CPLX1 GPC3 ADAM17 TERT ZMPSTE24 SATB2 DSP SASH1 AIRE COL7A1 CTC1 EDA ROR2 TTC7A NOP10 PLEC PLEC FZD6 VAC14 SUZ12 KRT14 ACTL6B PARN KDM1A KRT14 ARX PNKP IFT43 LAMA3 RAB7A KRT14 TRPV3 FTL LBR CRKL GABBR2 SLC25A24 MVK ITGB4 PLAGL1 MECP2 RERE FGF9 GTF2IRD1 UBA1 LAMA3 EED TSC1 LMNA KRT5 PHYH
Protein Mutations 1
N171K
SNP 0