PMID- 31025924
OWN - NLM
STAT- MEDLINE
DCOM- 20200717
LR  - 20200717
IS  - 0392-856X (Print)
IS  - 0392-856X (Linking)
VI  - 38
IP  - 1
DP  - 2020 Jan-Feb
TI  - Primary efficacy of netakimab, a novel interleukin-17 inhibitor, in the treatment 
      of active ankylosing spondylitis in adults.
PG  - 27-34
AB  - OBJECTIVES: Netakimab (NTK) is a humanised monoclonal antibody targeting 
      interleukin-17A, previously investigated in a phase 1 trial in healthy 
      volunteers. Here, we report the results of a phase 2 trial, conducted to assess 
      safety and pharmacokinetics (PK), to establish a therapeutic dose of NTK in a 
      target population of patients with active ankylosing spondylitis (AS). METHODS: 
      89 patients with active AS, despite non-steroidal anti-inflammatory (NSAID) drug 
      treatment, were randomised to receive 40, 80 or 120 mg of subcutaneous NTK or 
      placebo at weeks 0, 1, 2 and q2wk thereafter until week 12. The primary endpoint 
      was to achieve a proportion of patients with >/=20% improvement in Assessment of 
      Spondyloarthritis. RESULTS: Rates of ASAS20 response at week 16 for NTK with 
      95%CI for difference in ASAS20 rates NTK vs. placebo were 72.73% [1.69%;58.05%], 
      81.82% [12.36%;65.56%], 90.91% [23.71%;72.39%] at doses of 40, 80 and 120 mg. The 
      response rate in the placebo arm was 42.86%. The pre-specified margin of 
      clinically non-meaningful difference was 10%. Superiority to placebo was 
      confirmed for doses 80 and 120 mg. The most frequent adverse events (AEs) were 
      lymphocytosis, neutropenia, and asymptomatic bacteriuria. No dose-dependent 
      toxicity or serious adverse events (SAEs) were observed. The most effective dose 
      with the fastest response onset and favourable safety profile was 120 mg. 
      CONCLUSIONS: The data obtained demonstrate the efficacy and favourable safety 
      profile of NTK in active AS. Clinical development of NTK will be continued in a 
      phase 3 trial aimed to evaluate the efficacy of 1-year treatment with NTK 120 mg 
      in patients with AS.
FAU - Erdes, Shandor
AU  - Erdes S
AD  - Nasonova Research Institute of Rheumatology, Moscow, Russia.
FAU - Nasonov, Evgeny
AU  - Nasonov E
AD  - Nasonova Research Institute of Rheumatology, Moscow, Russia.
FAU - Kunder, Elena
AU  - Kunder E
AD  - Academy for Postgraduate Education, Minsk, Belarus.
FAU - Pristrom, Andrey
AU  - Pristrom A
AD  - Academy for Postgraduate Education, Minsk, Belarus.
FAU - Soroka, Nikolay
AU  - Soroka N
AD  - Belarus State Medical University, Minsk, Belarus.
FAU - Shesternya, Pavel
AU  - Shesternya P
AD  - Krasnoyarsk State Medical University, Krasnoyarsk, Russia.
FAU - Dubinina, Tatiana
AU  - Dubinina T
AD  - Nasonova Research Institute of Rheumatology, Moscow, Russia.
FAU - Smakotina, Svetlana
AU  - Smakotina S
AD  - Regional Clinical Hospital, Kemerovo, Russia.
FAU - Raskina, Tatiana
AU  - Raskina T
AD  - Kemerovo State Medical University, Kemerovo, Russia.
FAU - Krechikova, Diana
AU  - Krechikova D
AD  - Regional Clinical Hospital, Smolensk, Russia.
FAU - Povarova, Tatiana
AU  - Povarova T
AD  - Road Clinical Hospital, Saratov, Russia.
FAU - Plaksina, Tatiana
AU  - Plaksina T
AD  - Clinical Hospital, Nizhniy Novgorod, Russia.
FAU - Gordeev, Ivan
AU  - Gordeev I
AD  - City Clinical Hospital No. 15, Moscow, Russia.
FAU - Mazurov, Vadim
AU  - Mazurov V
AD  - North-Western State Medical University, St. Petersburg, Russia.
FAU - Reshetko, Olga
AU  - Reshetko O
AD  - Regional Clinical Hospital, Saratov, Russia.
FAU - Zonova, Elena
AU  - Zonova E
AD  - Municipal Clinical Inpatient Facility No. 1, Novosibirsk, Russia.
FAU - Eremeeva, Anna
AU  - Eremeeva A
AD  - JSC BIOCAD, St. Petersburg, Russia. eremeevaav@biocad.ru.
FAU - Chernyaeva, Ekaterina
AU  - Chernyaeva E
AD  - JSC BIOCAD, St. Petersburg, Russia.
FAU - Makulova, Tatiana
AU  - Makulova T
AD  - Institute for Medical Research, St. Petersburg, Russia.
FAU - Ivanov, Roman
AU  - Ivanov R
AD  - JSC BIOCAD, St. Petersburg, Russia.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20190416
PL  - Italy
TA  - Clin Exp Rheumatol
JT  - Clinical and experimental rheumatology
JID - 8308521
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Interleukin-17)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Double-Blind Method
MH  - Humans
MH  - Interleukin-17/*antagonists & inhibitors
MH  - Spondylitis, Ankylosing/*therapy
MH  - Treatment Outcome
EDAT- 2019/04/27 06:00
MHDA- 2020/07/18 06:00
CRDT- 2019/04/27 06:00
PHST- 2018/10/15 00:00 [received]
PHST- 2019/02/25 00:00 [accepted]
PHST- 2019/04/27 06:00 [pubmed]
PHST- 2020/07/18 06:00 [medline]
PHST- 2019/04/27 06:00 [entrez]
AID - 13535 [pii]
PST - ppublish
SO  - Clin Exp Rheumatol. 2020 Jan-Feb;38(1):27-34. Epub 2019 Apr 16.