A Phase 2, randomized, double-blind placebo-controlled study to test the efficacy and safety of KPL-301 in giant cell arteritis

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*1mg/dL within 6 weeks of Day 0
4. Remission of GCA at or before Day 0 (resolution of GCA symptom(s) and CRP <
1.0mg/dL or ESR < 20 mm in the
first hour), such that the subject can safely participate in the study and
follow the protocol defined
procedures, 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
oophorectomy, 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
must agree to refrain from donating sperm during this time period.

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 biologic 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 must have had values * 60% of predicted
for measurements performed and no uncontrolled lung disease. A subject*s
medical regimen should
not have been significantly intensified to control lung disease within 12 weeks
prior to Day 0.
21. History of chronic respiratory tract infections
22. Congestive heart failure of New York Heart Association classification III
or IV
23. At screening blood tests, any of the following:
a) Aspartate transaminase (AST) > 2 × upper limit of normal (ULN)
b) Alanine transaminase (ALT) > 2 × ULN
c) Hemoglobin < 75 g/L
d) Neutrophils < 1.5 × 109/L
e) Creatinine clearance (CrCl) <30 mL/min