MARS-17 Study in Adults with Pain due to Osteoarthritis of the Knee

• Research type

  Research Study

• Full title

  A multicentre randomized, double-blind, placebo controlled, dose-finding, Phase 2 study (MARS-17) of GSK3858279 in adult participants with moderate to severe pain due to knee osteoarthritis

• IRAS ID

  1007164

• Contact name

• Contact email

  GSKClinicalSupportHD@gsk.com

• Sponsor organisation

  GSK Research & Development Limited

• Eudract number

  2022-502799-22

• Clinicaltrials.gov Identifier

  NCT05838742

• Research summary

  Research Summary
  Arthritis is a condition that causes pain and swelling in the joints. Osteoarthritis (OA) is a most common type of arthritis affecting the small and large joints of the knees, hands, hips, and spine. It occurs when the cartilage that protects or cushions the ends of the bones in joints gradually worsen over time. Current available therapies provide modest improvement in pain and are associated with many side effects.

  This study will test a new drug GSK3858279 which is a monoclonal antibody in adult participants with moderate to severe pain due to knee osteoarthritis. The purpose of this study is to see if study drug GSK3858279 can reduce the knee pain in people with OA and to collect data on the safety of the drug and the levels of drug in the body. It will also help to determine what dose of the drug works best. The study is sponsored by GlaxoSmithKline.

  The study will involve around 420 adults who are between 40-80 years of age. Approximately 20 subjects will be enrolled in the UK. The total study period will be up to 36 weeks which includes a 5-week screening period, 16 weeks of treatment period and 15 weeks of off treatment follow- up period.

  GSK3858279 is delivered via an injection under the skin. All study participants will be divided into 5 groups. Four groups will receive different doses of GSK3858279 and 1 group will receive placebo.

  Tests undertaken will include but not limited to:
  - Blood tests
  - X-rays of the knee
  - Physical examination
  - Urine test
  - Questionnaires for daily knee pain, daily activities and quality of life

  Summary of Results
  This study was conducted to test whether GSK3858279 could help reduce knee pain in people with OA. GSK3858279 is a "new investigational medicine", which means that it has not yet been approved by health authorities for use by the general public.
  A total of 314 participants from 13 countries were enrolled in this study, 310 participants received the study medicine.

  Participants were included in the study if they:
  * Were above 40 years old.
  * Had painful osteoarthritis in the knee, with symptoms for 6 months or more and diagnosed by a doctor using specific medical guidelines.
  * Had an average knee pain score between 4 and 9 recorded at Visit 1, measured on a 0 to 10 pain scale.
  * Had an inadequate response to previous pain medications for OA treatment.
  Participants were excluded from this study if they had:
  * Any serious diseases related to the heart, kidney, stomach or lymph node.
  * Other joint diseases that could affect how their osteoarthritis symptoms are measured.
  * A serious injury or surgery to the knee or hip in the past 6 months

  This was a double-blind study, which means that neither the participants nor the study doctors were aware of the treatment given to the participants. THe study drug was GSK3858279 which is a monoclonal antibody, a special protein made in a laboratory given as an injection under the skin or a matching placebo. Participants received either a placebo or different doses of GSK3858279 once a week or every two weeks.

  An early analysis was conducted after about 120 participants completed their Week 12 visit. The results indicated that GSK3858279 was not as effective as intended, hence the study ended earlier than planned.
  Importantly, the decision to stop the study by the sponsor, GSK, was not due to any safety concerns related to the medicine GSK3858279. The study remained focused on ensuring that participants completed a follow-up visit approximately 16 weeks after their last dose, in order to formally conclude the study.

  Study doctors looked at how well GSK3858279 helped reduce knee osteoarthritis (OA) pain compared to a placebo. They measured this by checking the change in average knee pain from Day 1 to Week 12, using a pain scale from 0 (no pain) to 10 (worst pain).

  Participants recorded their pain daily in a digital diary. Each week's average pain score was compared to the starting score. A lower score means their pain has improved, the lower the score, the greater the reduction in pain.

  There was no sign that the medicine GSK3858279 helped reduce knee pain compared with placebo.

  1 out of 50 participants (2%) in the GSK3858279 60 mg weekly group reported a serious side effect, Herpes Zoster also known as Shingles. This is a painful skin rash caused by the virus that causes chickenpox. Herpes zoster was resolved with one month. No serious side effects were observed in other treatment groups. None of the participants in this study died because of side effects.
  The non-serious side effects reported by at least more than 2% participants in either of the treatment groups were:
  A decrease in kidney function to filter out waste from the blood.
  Allergic reaction at injection site
  An infection in the nose, throat, or sinuses Bruising at the site of injection Headache redness at site of injection Reaction at the site of injection

  Researchers concluded that the study did not find clear evidence that GSK3858279 worked better than placebo in reducing knee pain or improving movement. The safety results were similar to what was already known about the medicine, with no new safety concerns. There are no further studies planned on GSK3858279.

• REC name

  Wales REC 5

• REC reference

  23/WA/0141

• Date of REC Opinion

  25 Aug 2023

• REC opinion

  Further Information Favourable Opinion