SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00716014

Developed by Shray Alag, 2019.
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: Nails, Malformed Pachyonychia Congenita
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

Foot 1

Name: Normal saline (placebo)

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

Type: Drug

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:
Abnormality of the nail
Genes 357
PIGN TRAF3IP2 IL11RA GDF5 UBR1 SOX11 HGD TCTN3 TREX1 ATP6V1B2 KLHL24 CDSN ABCA1 ERCC2 TRAF6 EED ERCC3 EOGT PDE4D NOG ZBTB20 ZMPSTE24 ATR ACD KIF1A RTEL1 ABCA12 CWC27 KRT74 GJB4 C15ORF41 CTSC GJB6 INPPL1 RPS6KA3 APC2 RNF113A INSR TRPS1 PTDSS1 CPLX1 PEPD PEX1 CLEC7A PEX6 ITGA6 PEX7 ACTG2 DNAJC21 EVC SOX18 FGFRL1 IRF6 SRY TSC1 RSPO4 TSC2 SMARCAD1 TMEM173 KCTD1 ITGA3 ACVRL1 GPR101 SRCAP PTEN ARID1A EZH2 BCR WNK1 NSUN2 GRHL2 IL17F ITGB4 MECP2 DPM1 IFT43 STAT3 TBC1D24 RNU4ATAC FAM111B NSDHL SLC35D1 STIM1 FZD6 IFIH1 CDKL5 GJA1 HOXA13 BMP2 STK11 BMP4 JUP PHYH BMPR1B GJB2 GJB3 ARID1B UBA1 UBE2A DST STXBP1 PNPLA1 HOXC13 PIGA GPC3 MBTPS2 BRAF EDAR SULT2B1 TINF2 FIG4 WASHC5 ARHGAP31 CARD9 POMP KCNH1 GLI1 ACAN HPGD GLI3 EDARADD RAB3GAP2 NFKB2 RECQL4 NECTIN1 PITX1 POP1 GPC4 RETREG1 SCN9A HRAS WDR35 PKP1 GTF2H5 NECTIN4 RAB7A DKC1 ANTXR1 UMPS PLAGL1 COL14A1 FGF9 AKT1 GNA11 TRPV3 NOP10 DLX3 FGFR1 ADAM17 DLX5 PLCD1 IL17RA FGFR2 MMP1 TAF1 BMPER PLEC FTO UROD FHL1 DOCK6 HYMAI KDF1 ALOX12B FOXG1 TAT NOTCH1 NOTCH2 CARD14 KIF11 KIF22 FOXP3 FOXC2 COL2A1 VEGFC KRAS SLC25A24 FOXN1 KRT1 DPH1 NDUFB11 FLNA KRT5 FLNB KRT6A COL7A1 KRT6B TBX3 NIPAL4 KRT9 NPR2 SATB2 SOST FLT4 COL11A1 KRT14 COL11A2 EVC2 TBX4 CCDC22 PLOD3 COL17A1 KRT16 POC1A KRT17 SASH1 OFD1 USB1 DSG1 CLIP2 DLL4 DSP CTC1 WHCR NSD2 PPM1D KRT81 KRT83 NTRK1 WNT5A KRT85 KRT86 WNT7A ROR2 BHLHA9 ARX FERMT1 CAST DVL1 SLURP1 DVL3 APC NSD1 IKBKG COX7B LAMA3 AIRE NTNG1 BAZ1B PORCN B3GALT6 SHOX LAMB3 NLRP1 GJC2 CASR LAMC2 SLC39A4 IL17RC LIPN RIPK4 ZSWIM6 AIP DPF2 LBR HUWE1 RUNX2 RFC2 WRAP53 CPT2 GABBR2 GTF2IRD1 ECE1 PIGV NHP2 PQBP1 TERC SHOC2 AAGAB TERT NXN EDA TFAP2A SHANK3 LETM1 ATL1 CRKL POLR3A STAMBP PPP1CB SDR9C7 WDR19 TTC7A ORC1 MSX1 TGM1 MLXIPL LIG4 LIMK1 SETD2 GTF2E2 VAC14 RAB3GAP1 GTF2I IFT52 EFNB1 IL36RN LMNA DYNC2LI1 LMX1B CD28 LOR LPAR6 TP63 SLCO2A1 ARID2 SETBP1 CERS3 EBP RLIM RBPJ CSTA MPLKIP PRKAR1A SMARCA4 CKAP2L LRP4 SMARCB1 WNT10A SMARCC2 CYP4F22 SMARCD2 SMARCE1 CTBP1 WDR73 ALOXE3 FTL CD151 PARN ALG3 PRKD1 DSG4 IFT122 CTLA4 FUCA1 ELN SUZ12 MAPK1 IHH TNFRSF1B KDSR MAP2K1 MAP2K2 ENG CDH1 FZD2 ATP2A2 MCTP2 CTSK RSPO1 HCCS TBL2 KDM1A MVK ADAMTSL2 ATP6V0A2 MAF