giant cell arteritis MedDRA version: 20.0 Level: LLT Classification code 10018250 Term: Giant cell arteritis System Organ Class: 100000004866
Conditions
Interventions
Product Name: Mavrilimumab
Product Code: KPL-301
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: MAVRILIMUMAB
CAS Number: 1085337-57-0
Current Sponsor code: KPL
Sponsors
Kiniksa Pharmaceuticals, Ltd. (Hamilton, Bermuda) c/o Kiniksa Pharmaceuticals Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to provide written informed consent and to comply with the study protocol 2. Age of = 50 to 85 inclusive 3. Diagnosis of new-onset or relapsing GCA classified according to the following criteria: New-onset: Initial diagnosis of GCA within 6 weeks of Day 0, defined as: a) Westergren ESR > 30 mm/hour or CRP = 1 mg/dL b) AND at least one of the following: i. Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp or temporal artery pain or tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication) ii. Unequivocal extracranial symptoms of GCA such as claudication of the extremities iii. Symptoms of PMR, defined as shoulder and/or hip girdle pain associated with inflammatory morning stiffness c) AND at least one of the following: i. TAB or ultrasound revealing features of GCA ii. Evidence of large-vessel vasculitis by angiography or cross-sectional imaging study such as MRI, CT/CTA, or PET-CT of the aorta or other great vessels Relapsing: Diagnosis of GCA > 6 weeks before Day 0 AND: Active GCA within 6 weeks of Day 0 defined as clinical sign/symptom(s) as per above and Westergren ESR> 30 mm/hour or CRP = 1 mg/ dL Refractory nonremitting: Diagnosis of GCA > 6 weeks before Day 0 AND No remission since the diagnosis of disease as per clinical expectations. i.e. Presence of sign/symptoms as per above and Westergren ESR>30mm/hour or CRP = 1 mg/ dL within 6 weeks of Day 0 4. Remission of GCA at or before Day 0 (resolution of GCA symptom(s) and CRP < 1.0 mg/dL or ESR < 20 mm in the first hour), such that the subject can safely participate in the study and follow the protocol defined rocedures, including initiation of the prednisone taper at the protocol-specified starting dose (i.e., =60 mg/day) 5. At Day 0, receiving or able to receive oral prednisone up to 60 mg/day for the treatment of GCA 6. If using methotrexate (MTX), oral or parenteral up to 25mg/week is permitted in screening if started more than 6 weeks prior to Day 0 and should be tapered to zero by Day 0. 7. Willing to receive antiplatelet therapy depending on the Investigator’s decision 8. Willing to receive treatment for prevention of corticosteroid-induced osteopenia/osteoporosis depending on the Investigator’s decision 9. Female subjects must be: a) postmenopausal, defined as at least 12 months post cessation of menses (without an alternative medical cause), or b) permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral ophorectomy, or tubal ligation or having a male partner with vasectomy as affirmed by the subject, or c) nonpregnant, nonlactating, and if sexually active having agreed to use a highly effective method of contraception (i.e., hormonal contraceptives associated with inhibition of ovulation or intrauterine device [IUD], or intrauterine hormone-releasing system [IUS], or sexual abstinence) from Screening visit until the final Washout Safety Follow-up visit 84 ± 3 days from EOT Visit. 10. Male subjects must have documented vasectomy or if sexually active must agree to use a highly effective method of contraception with their partners of childbearing potential (i.e., hormonal contraceptives associated with the inhibition of ovulation or intrauterine device [IUD], or intrauterine hormone-releasing system [IUS], or sexual abstinence) from Day 0 until the final Washout Safety Follow-up visit 84± 3 days from EOT Visit. Male subjects mus
Exclusion criteria
Exclusion criteria: General Exclusion Criteria 1. Major surgery within 8 weeks prior to Screening or planned major surgery within 12 months after randomization 2. Transplanted organs (except corneal transplant performed more than 3 months prior to randomization) 3. Major ischemic event unrelated to GCA within 12 weeks of Screening Exclusions Related to Prior or Concomitant Therapy 4. Concurrent enrollment in another clinical study, with the exception of observational studies 5. Previous treatment with KPL-301 6. Treatment with any non-biologic investigational drug therapy within 4 weeks or 5 half-lives of the study agent, whichever was longer, prior to Screening 7. Any cell-depleting biological therapies (e.g., anti-CD20) within 12 months prior to Day 0; or previous treatment with noncell-depleting biological therapies (such as anti-tumor necrosis factor [TNF], anakinra, anti-Interleukin [IL]-6 receptor [e.g. tocilizumab], or abatacept) within 8 weeks (or 5 half-lives, whichever is longer) prior to Screening 8. Treatment with alkylating agents within 12 weeks prior to Screening 9. Intramuscular, IV corticosteroids, Intra-articular corticosteroids within 4 weeks prior to Screening 10. Receipt of live (attenuated) vaccine within the 4 weeks before Day 0 11. Treatment with hydroxychloroquine, cyclosporine A, azathioprine, cyclophosphamide, or mycophenolate mofetil (MMF) within 4 weeks of Screening Relating to Medical History 12. Female subjects who are pregnant, intending to become pregnant, or are breastfeeding 13. Any condition that, in the opinion of the Investigator, could interfere with evaluation of KPL-301 or interpretation of subject safety or confound the results of the study 14. Known history of allergy or reaction to any component of the KPL-301 or placebo formulation or to any other biologic therapy or prednisone or any of its excipients 15. Positive (or 2 indeterminate) QuantiFERON test results. 16. Clinically significant active infection including signs/symptoms suggestive of infection, any significant recurrent or chronic infection (including positive hepatitis C virus antibody [HCVAb]), or any episode of infection requiring hospitalization or treatment with IV antibiotics within 12 weeks before Screening. Subjects with any opportunistic infection within 6 months before Screening will be excluded from the study. 17. Subjects with chronic active hepatitis B infection as defined below will be excluded from the study: ? Hepatitis B surface antigen (HbsAg) positive ? Hepatitis B anti-core antibody positive but anti-surface antibody negative 18. Subjects at a high risk of infection (e.g., history of hereditary or acquired immune deficiency disorder including a history of known human immunodeficiency virus [HIV] infection), a history of an infected joint prosthesis at any time with that prosthesis still in situ, leg ulcers, indwelling urinary catheter, or persistent or recurrent chest infections 19. History of cancer within the last 10 years - except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured 20. Evidence of clinically uncontrolled respiratory disease. The Investigator should review the data from subjects’ respiratory assessments including chest x-ray and pulmonary function tests (PFTs) including DLCO performed during the screening period or within 12 weeks prior to Day 0 if results of prior assessments are available. Available PFT and DLCO assessments mus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of KPL-301 versus placebo, coadministered with a 26-week steroid taper, for maintaining sustained remission for 26 weeks in subjects with newonset or relapsing/refractory giant cell arteritis (GCA).;Secondary Objective: The secondary objectives of the study, in subjects with new-onset and relapsing/refractory GCA, are: a) To evaluate the effect of KPL-301 vs placebo on cumulative corticosteroid dose. b) To evaluate the effect of KPL-301 vs placebo on health-related quality of life (HRQoL). c) To evaluate the safety and tolerability of KPL-301. d) To evaluate the pharmacokinetics (PK) of KPL-301.;Primary end point(s): Time to flare by week 26 defined as time from randomization to the first flare occurring within the first 26-weeks of the double-blind period;Timepoint(s) of evaluation of this end point: Appro. 32 weeks after the start of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to flare by week 26 from randomization to first flare occurring within the first 26 weeks of the double-blind period in the per protocol population Percentage of subjects who have completed the 26-week corticosteroid taper and who have a normal ESR Percentage of subjects who have completed the 26-week corticosteroid taper and who have a normal CRP Percentage of subjects who completed the 26-week corticosteroid taper and who have no signs/symptoms of GCA Time to corticosteroid dose of zero mg/day Cumulative steroid dose at Week 26 and at the end of the Washout Safety Follow-up Period Change in clinical GCA assessments (including NRS and FACIT) over time Change in quality-of-life over time ;Timepoint(s) of evaluation of this end point: Appro. 44 weeks after the start of the study | — |
Countries
Australia, Belgium, Croatia, Estonia, Germany, Ireland, Italy, Netherlands, New Zealand, Poland, Serbia, Slovenia, Spain, United Kingdom, United States
Contacts
Public ContactKiniksa Medical Information Group
Kiniksa Pharmaceuticals, Ltd. (Hamilton, Bermuda) c/o Kiniksa Pharmaceuticals Corp.
Outcome results
None listed