Conditions: Giant Cell Arteritis Temporal Arteritis Horton's Disease
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 13
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine whether ustekinumab is effective in the treatment of Giant Cell Arteritis (GCA)

Detailed description:
The objective of this study is to evaluate the efficacy and safety of ustekinumab, an interleukin (IL)-12/23 inhibitor, in patients with GCA

Hypothesis IL-12/23 pathway blockade may maintain disease remission in patients with GCA

Specific Aims

* To evaluate the safety and tolerability of ustekinumab administration in 20 patients with GCA
* To evaluate the efficacy of ustekinumab for remission maintenance and glucocorticoid sparing in 20 patients with GCA

Arms:
arm 1: 1. Ustekinumab: 90 mg of ustekinumab will be administered subcutaneously at baseline, week 4, week 12, week 20, week 28, week 36 and week 44.
2. Prednisone: All patients will receive a prednisone course tapered according to predefined schedules starting at either 60 mg, 40 mg or 20 mg. The initial dose of prednisone will be chosen by the investigators according to disease severity and comorbid medical conditions. The duration of the prednisone taper will be 6 months in all cases.

Interventions: intervention 1: Ustekinumab intervention 2: Prednisone
Intervention descriptions: intervention 1: Ustekinumab is a humanized monoclonal antibody that targets the p40 subunit of IL-12 and IL-23 and inhibits cytokine - cytokine receptor coupling and signaling intervention 2: Prednisone is an anti-inflammatory medication

Protocol document:
Prot_SAP_000.pdf: 
 
1
 
PARTNERS HUMAN RESEARCH COMMITTEE 
DETAILED PROTOCOL 
 
Massachusetts General Hospital  
55 Fruit Street 
Boston, MA 02114 
 
Study title 
USTEKINUMAB FOR THE TREATMENT OF GIANT CELL ARTERITIS 
Study Drug 
Ustekinumab (Stelara) 
 
Study Drug and Financial Support Provided By 
Janssen Scientific Affairs, LLC 
 
Sponsor Investigator 
Sebastian Unizony, MD 
 
Co-investigators 
John H. Stone, MD, MPH 
Cory A Perugino, DO 
 
Research Manager 
Ana Fernandes 
 
Protocol Number 
2016P000932 
 
Version 3: February 20, 2019  
ClinicalTrials.Gov Number 
 NCT02955147 


 
2
I. BACKGROUND AND SIGNIFICANCE 
a. Clinical background and unmet need 
Giant Cell Arteritis (GCA) is the most common form of primary vasculitis among adults 
in Western countries, with a prevalence ranging from 24 to 280 cases per 100,000 
individuals older than 50. The incidence of GCA increases progressively with age and 
peaks during the eighth decade of life. The disease has a particular predilection for 
populations of northern European ancestry and is approximately twice as common in 
women than in men [1]  
 
The main histopathologic feature of GCA comprises a chronic granulomatous 
inflammatory process that involves the aorta and its main branches, with a tendency to 
affect the extracranial carotid arteries and the ophthalmic circulation [1]. The clinical 
manifestations consist of constitutional symptoms (e.g., asthenia, fever), headaches, jaw 
pain, scalp tenderness, visual symptoms (e.g., blurry vision, amaurosis fugax, diplopia), 
shoulder and hip girdle pain and stiffness (i.e., polymyalgia rheumatica) and elevated 
acute-phase reactants. The most important complication of GCA is vision loss, which 
occurs in 15% of cases. Other possible complications include aortic aneurysm, limb 
claudication from large-artery stenosis (particularly the subclavian and axillary arteries), 
stroke, mesenteric ischemia, myocardial infarction and venous thromboembolism [1] 
 
No curative treatment currently exists for GCA. However, glucocorticoids (prednisone) 
are able to control the clinical evidence of inflammation when administered in moderate 
to high doses . Unfortunately, 40-85% of the patients experience disease relapses upon 
glucocorticoid tapering or discontinuation [2-8]. Such patients require frequent re-
treatment and most of them develop undesirable side effects form prolonged 
glucocorticoid exposure [9]. Long-term glucocorticoid therapy is associated with adverse 
events in approximately 86% of the patients, including osteoporotic fractures, diabetes 
mellitus, 
infection, 
cataracts, 
hypertension, 
femoral 
avascular 
necrosis, 
and 
gastrointestinal bleeding [9, 10]. In most cases, glucocorticoid-related toxicity becomes 
more problematic to patients than the disease itself. 
 


 
3
No medication except glucocorticoids has been shown convincingly to be effective in 
suppressing the activity of GCA. The use of other immunosuppressive medications, 
including methotrexate, azathioprine, cyclophosphamide, and tumor necrosis factor 
(TNF) antagonists has been generally unsuccessful [7, 11-14]. Sudies using the 
interleukin (IL)-6 receptor inhibitor tocilizumab are ongoing [15]. There is currently a 
great unmet need for specific disease modifying agents to maintain disease remission in 
GCA, and therefore reduce the exposure to and the toxicity associated with 
glucocorticoids. 
 
b.    Pre-clinical and clinical studies leading up to and supporting the proposed 
research 
Role of interleukin (IL)-12 and IL-23 in autoimmune diseases 
IL-12 and IL-23 play important roles in regulating physiologic T-cell immune responses. 
IL-12 drives the differentiation of naïve T helper (Th) cells towards the Th1 cell 
phenotype [16], and IL-23 acts in concert with IL-6, IL-1β and transforming growth 
factor (TGF)- to promote the generation and maintenance of Th17 cells [17, 18]. Once 
differentiated, Th1 and Th17 cells produce the effector cytokine interferon (IFN)- and 
IL-17, respectively 
 
Although the activation of the Th1 and Th17 pathways is crucial for generating immunity 
against a variety of microorganisms, the deregulation of these mechanisms has been 
described in several immune-mediated diseases. IL-12 and IL-23 are important mediators 
in experimental models of psoriasis [19, 20], Crohn’s disease [21], multiple sclerosis 
(MS) [22], rheumatoid arthritis [23], and thyroiditis [24]. In humans, IL-12 and IL-23 
have been implicated in the pathogenesis of psoriasis [25], Crohn’s disease [26, 27], MS 
[28], RA, and recently GCA [29-32] (see below).  
 
Ustekinumab ameliorates Th1 and Th17 responses in vitro and in vivo  
IL-12 and IL-23 are heterodimeric cytokines that have a common p40 subunit. A 
functional IL-12 molecule consists of a p40 and a p35 subunit, and a functional IL-23 
molecule consists of a p40 and a p19 subunit. On the other hand, IL-12 and IL-23 


 
4
receptors are also heterodimers that share the same IL-12Rβ1 chain. Whereas IL-12Rβ1 
is responsible of binding to p40, the second receptor component, namely IL-12Rβ2 for 
IL-12 receptor and IL-23R for IL-23 receptor, is cytokine-specific, and mediates signal 
transduction upon binding to p35 and p19, respectively  
 
Ustekinumab is a fully human IgG1-kappa monoclonal antibody that specifically binds 
with high affinity to the shared p40 subunit of the cytokines IL-12 and IL-23 (IL-
12/23p40) and blocks the cytokine-cytokine receptor coupling, thereby preventing the 
initiation of the signaling cascade that leads to the generation and activation of Th1 and 
Th17 cells, and the production of IFN- and IL-17 [33, 34] (Figure 1. IL-12 and IL-17 
pathways and ustekinumab mechanism of action).  
 
By preventing IL-12/23p40 ligation to IL-12Rβ1, ustekinumab neutralizes the following 
IL-12 (Th1) and IL-23 (Th17) mediated in vitro cellular responses: 
- 
Intracellular phosphorylation of STAT 4, STAT 6 and production of INF- (Th1) 
- 
Intracellular phosphorylation of STAT 3 and production of IL-17A, IL-22, and 
IL-17F (Th17) 
 
Ustekinumab was approved by the FDA in 2009 for the treatment of moderate to severe 
plaque psoriasis requiring systemic therapy based on 3 randomized controlled trials [35-
37]. Besides the observed clinical response, serial skin biopsies in patients with psoriasis 
treated with ustekinumab showed decreased T-cell infiltrates and reduced gene 
expression of IL-12p40, IL-23p19, and IFN- [38]. 
 
Some evidence suggests that IL-12/IL-23p40 targeted treatment may also be beneficial in 
Crohn’s disease [39], psoriatic arthritis [40, 41], and ankylosing spondylitis [42, 43] 
 
Two distinct pathways driven by Th17 and Th1 cells contribute to the pathogenesis 
of GCA.  
The etiology of GCA is not known. However, the mechanisms that perpetuate vascular 
inflammation in this disease are partially understood. In untreated patients, CD4-positive 


 
5
T lymphocytes, mainly IFN-producing Th1 cells and IL-17-secreting Th17 cells, 
infiltrates large- and medium- sized arteries [29, 44-48]. Mirroring vascular 
inflammation, flow cytometry studies have demonstrated that Th1 and Th17 cell 
frequencies are also expanded in peripheral blood during periods of disease activity [29, 
45, 46].  
 
Doses of prednisone used in clinical practice significantly reduce the arterial infiltration 
of Th17 cells and normalize Th17 cell blood stream expansion [29, 45, 46]. Increased 
serum level of Th17-related cytokines (e.g., IL-6, IL-23, IL-1, and IL-17) rapidly 
decline with glucocorticoid treatment [29, 49]. On the other hand, reports regarding the 
effects of glucocorticoids on the abnormalities of the Th1 axis are contradicting [29, 31, 
32], with some reports describing persistance of the arterial Th1 infiltrates and the IL-12 
and IFN serum and tissue up-regulation even after 3-9 months of therapy [29] 
The pathogenesis of GCA supports the hypothesis that the down-regulation of the Th1 
and Th17 pathways by blocking IL-12 and IL-23 signaling could allow patients to stay in 
remission off glucocorticoid therapy (See figure 1) 
 
 Pre-clinical safety of ustekinumab [50] 
In cynomolgus monkeys, ustekinumab was well-tolerated following IV doses up to 45 
mg/kg/week for up to a month, and following twice weekly subcutaneous doses up to 45 
mg/kg for 6 months. Except for one case of bacterial enteritis, no ustekinumab-related 
mortality or adverse events were reported, and there was no tumor, pre-neoplastic or 
other histological abnormality in necropsy studies. Immunotoxicity evaluations showed 
no alteration on lymphoid organ weight or histology; abnormalities on blood counts or 
lymphocyte subpopulations; nor adverse effects on immune response to neoantigen 
(KLH), delayed type hypersensitivity responses, or ex vivo lymphoproliferative 
responses to T cell mitogens. No adverse events were seen in an acute asthma model 
carried out given theoretical increased risk of exacerbation of Th2-driven pathologies 
with Th1 blocking agents. Ustekinumab did not show developmental toxicity, 
teratogenicity, or reproductive toxicity. The no observed adverse effect level (NOAEL) 


 
6
for ustekinumab in general, developmental and reproductive toxicity studies was 45 
mg/kg. The cumulative dose in the 6-month chronic toxicity study (45 mg/kg twice 
weekly for 26 weeks) was 2340 mg/kg. Based on the proposed dosing, a GCA participant 
who has 50 Kg of weight would receive ustekinumab doses of < 2 mg/kg  (>22-fold 
lower than the NOAEL dose). In addition, based on the proposed dosing, upon 
completing the study a GCA patient who has 50 Kg of weight would receive 12.6 mg/kg 
(cumulative dose >180-fold lower than the dose given chronic toxicity studies) 
 
 Prior clinical experience with ustekinumab 
Summary of clinical efficacy [50] 
Ustekinumab has shown efficacy with adequate safety profiles in psoriasis, and psoriatic 
arthritis (PsA) 
 
Ustekinumab was approved by the FDA in 2009 for the treatment of adults with chronic 
moderate to severe plaque psoriasis.  The psoriasis clinical development program 
consisted of 3 well-controlled Phase 2 and Phase 3 clinical trials that evaluated 
subcutaneous doses of 45 and 90 mg as monotherapy in a total of 2266 subjects [51-53]. 
In these studies, ustekinumab led to rapid, clinically significant, and sustained 
improvement of psoriatic skin lesions.  
 
At week 28, over 90% of the subjects were Psoriasis Area and Severity Index (PASI) 50 
responders in both the 45 mg and 90 mg groups, at least 70% of subjects achieved a PASI 
75 response, and approximately 50% of subjects achieved a PASI 90 response. Clinical 
response was maintained with every 12 weeks administrations through 1 year in nearly 
90% of long-term responders (PASI 75 response at 28 and 40 weeks).  
 
Summary of clinical safety [50, 54] 
Data pertaining to the safety of ustekinumab comes from 2266 exposed subjects during 
the psoriasis trials (1970 subjects received at least 6 months of ustekinumab, 1285 
subjects were exposed for at least 1 year, and 373 underwent at least 18 months of 
treatment).  


 
7
 
The rate of adverse events was similar in the placebo (50.4%), ustekinumab 45 mg 
(57.6%) and ustekinumab 90 mg (51.6%) groups. The risk of adverse events (AE) and 
serious adverse events (SAE) did not increase with the duration of exposure. Common 
AE tended to be mild and self-limited and included nasopharyngitis, upper respiratory 
infection, and headache. Dizziness, back pain, myalgia, injection-site erythema (1.3% 
ustekinumab, 0.4% placebo), ecchymosis, diarrhea, and pharyngolaryngeal pain were 
slightly more frequent in the ustekinumab group. 
 
For all mortality causes, 8.11 deaths were expected through the data cutoff for the BLA, 
and only 1 death due to idiopathic dilated cardiomyopathy was reported. Three additional 
deaths were reported during phase 3 extension from causes unlikely related with the 
study drug (alcohol intoxication, post-operative bleeding, and metastatic renal cancer) 
 
Serious adverse events were reported in 1.4%, 1.6%, and 1.4% of the patients in the 
placebo, 45 mg, and 90 mg groups, respectively, through week 12. Serious adverse event 
rate did not increase over time.  
 
Serious infections were reported at a rate of 1.70 (95% CI, 0.35; 4.96) per hundred 
subject-years of follow up in the placebo group compared with 0.49 (95% CI, 0.01, 2.74) 
and 1.97 (95% CI, 0.54; 5.03) in subjects in the 45 mg and 90 mg ustekinumab groups, 
respectively.  
 
Malignancies were reported in 3 placebo-treated subjects (2 of 3 were non melanoma 
skin cancer), and 4 ustekinumab-treated subjects (3 of 4 were non melanoma skin 
cancer). Overall rates of malignancies per hundred subject-years of follow up were 
comparable in both groups. 
 
Through the data cutoff for the BLA, the rates of major adverse cardiovascular events 
(MACE) per hundred subject-years of follow up were comparable between groups. Rates 
of MACE were consistent with expected background rates. [55]. 


 
8
 
The overall incidence of antibodies to ustekinumab was 3.7% in the combined Phase 3 
studies and did not differ across doses nor increase over time. There was no evidence of 
lymphocyte depletion; alteration on the proportion of naïve (CD45RA), memory 
(CD45RO), or activated T lymphocytes; or ex-vivo PBMC production of IFN- or IL-5. 
Ustekinumab did not impact in non-memory antibody response (pneumococcal vaccine) 
or antigen recall response (tetanus toxoid).  
 
Safety of ustekinumab was consistent in all subpopulations including subjects >65 years 
of age. 
 
The 120-day safety update did not show increase in the rates of adverse events, serious 
adverse events, serious infections, malignancies, and serious cardiovascular events. 
 
Multiple subsequent studies have demonstrated similar safety profiles without 
unexpected adverse events. Some of these studies have used ustekinumab doses 
equivalent or higher to the dose proposed in this GCA study [41-43]  
 
Clinical pharmacology  
The SC bioavailability of the drug is 57.2% and after a single SC dose, ustekinumab 
reaches a maximum serum concentration in 7 to 14 days. The median volume of 
distribution ranged from 57 mL/kg to 83 mL/kg (intravascular space), and through the 
endogenous gammaglobulin metabolic pathway (reticuloendothelial system) ustekinumab 
is eliminated from the system with a median half-life of 3 weeks. In population PK 
analysis, only weight, diabetes and positive immune response status to ustekinumab 
affected the systemic exposure of the drug. No formal drug-drug interaction studies were 
conducted with ustekinumab. 
 
c.    Rationale behind the proposed research, and potential benefits to patients and 
society 


 
9
Given its mechanism of action, ustekinumab will specifically target important pathogenic 
pathways of GCA, and consequently may help maintain the disease in clinical remission 
while reducing the requirements of glucocorticoids (steroid-sparing effect).  
 
Remission maintenance and glucocorticoid-sparing effects may prevent or ameliorate the 
morbidity associated with GCA and the prolonged glucocorticoid exposure that this 
disease usually requires, improving the quality of life of the patients. In addition, if 
effective, the use of ustekinumab may reduce the costs of treating glucocorticoid-related 
side effects (e.g., osteoporotic fractures, diabetes mellitus, infections, cataracts, 
hypertension, femoral avascular necrosis, steroid induced myopathy, and gastrointestinal 
bleeding). Finally, ustekinumab may add to the limited therapeutic options currently 
available for GCA. 
 
II SPECIFIC AIMS 
The objective of this study is to evaluate the efficacy and safety of ustekinumab, an IL-
12/23 inhibitor, in patients with GCA 
 
Hypothesis 
IL-12/23 pathway blockade with ustekinumab maintains disease remission in patients 
with GCA  
 
Specific Aims 
 To evaluate the safety and tolerability of ustekinumab administration in 20 patients 
with GCA  
 
 To evaluate the efficacy of ustekinumab for remission maintenance and 
glucocorticoid sparing in 20 patients with GCA  
 
 
III. SUBJECT SELECTION 


 
10 
a. Inclusion Criteria (Subjects must meet the following criteria to be considered 
eligible for study entry): 
1) Able and willing to provide written informed consent and to comply with the 
study protocol 
 
2) Diagnosis of GCA classified according to the following criteria: 
• Age 50 years or older 
• History of ESR ≥ 50 mm/hour or CRP ≥ 10 mg/L 
 
AND at least one of the following: 
• Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp 
tenderness, temporal artery tenderness or decreased pulsation, ischemia-related vision 
loss, or otherwise unexplained mouth or jaw pain upon mastication) 
 
• Symptoms of polymyalgia rheumatica (PMR), defined as shoulder and / or hip girdle 
pain associated with inflammatory morning stiffness 
 
AND at least one of the following: 
• Temporal artery biopsy revealing features of GCA (e.g., mononuclear cell infiltration or 
granulomatous inflammation). 
 
• Evidence of large-vessel vasculitis by angiography or cross-sectional imaging study 
such as MRA, CTA, or PET-CT 
 
3) New-onset or refractory active disease defined as follows: 
• New onset: diagnosis of GCA within 6 weeks of Baseline visit 
 
• Refractory: diagnosis of GCA > 6 weeks before Baseline visit and previous treatment 
with 40 mg/day prednisone (or equivalent) for at least 2 consecutive weeks at any time 
 
AND 


 
11 
 
• Active GCA within 6 weeks of Baseline visit (active disease defined as the presence of 
clinical signs and symptoms [cranial or PMR] and ESR ≥ 30 mm/hour or CRP ≥ 10 
mg/L)* # 
 
*ESR ≥ 30 mm/hour or CRP ≥ 10 mg/L is not required if active GCA has been confirmed 
by a positive temporal artery biopsy within 6 weeks of the Baseline visit 
# Prior treatment with tocilizumab normalizes CRP and ESR values therefore these inflammatory 
markers cannot be used monitor disease activity. For patients who are failing treatment with 
tocilizumab due to flare, elevation of ESR and/or CRP is not required in the definition of active 
disease for eligibility purposes.  
 
b. Exclusion Criteria 
Patients who meet any of these criteria will not be enrolled in this study 
 Comorbidities 
- Allergies: Subjects who have history of previous severe allergic or anaphylactic reaction 
associated with the administration of monoclonal antibodies or antibody fragments or 
excipients to ustekinumab. 
- Systemic infection: Subjects who have an active systemic infection. 
- Serious infection: Subjects who have had serious infections (e.g., pneumonia, or 
pyelonephritis), or any major episode of infection requiring hospitalization or treatment 
with IV antibiotics within 4 weeks of enrollment.  
- Chronic or recurrent infection: Subjects who have chronic or recurrent bacterial, viral, 
fungal, mycobacterial (e.g., tuberculosis and other atypical mycobacterial disease), or 
protozoan infection. 
- Opportunistic infection: Subjects who have, or have had, an opportunistic infection 
(e.g., cytomegalovirus, 
coccidioidomycosis, 
Pneumocystis 
carinii, aspergillosis, 
histoplasmosis, or mycobacterium) within 6 months prior to enrollment. 
- Blood borne infection: Subjects who have active hepatitis B or active hepatitis C or a 
documented history of HIV, hepatitis B, or hepatitis C.  


 
12 
- Latent tuberculosis infection (LTBI): Subjects who have untreated LTBI are ineligible. 
Patients with LTBI are eligible for enrollment one month after initiating treatment for 
LTBI. 
- Malignancy: Evidence of malignant disease or malignancies diagnosed within the 
previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in 
situ of the cervix uteri that have been excised and cured) 
- Uncontrolled disease: Subjects with evidence of serious uncontrolled concomitant 
cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, immunologic, 
psychiatric (incl. drug or alcohol abuse) or gastrointestinal disease that could interfere 
with participation in the trial according to the protocol. 
- Transplanted organs: Subjects with transplanted organs (with the exception of a corneal 
transplant > 3 months prior to screening). 
- Major surgery within 8 weeks prior to Screening or planned major surgery within 12 
months after Baseline 
- Pregnancy 
 
 Prohibited medications:  
- Subjects who received immunosuppressive agents [e.g., methotrexate (MTX) > 30 mg 
weekly, azathioprine, mycophenolate mofetil, cyclophosphamide, chlorambucil, 
tacrolimus, leflunomide]; IL-1 antagonists (e.g., anakinra, canakinumab); B-lymphocyte 
stimulator (BLyS) inhibitors (e.g., belimumab); co-stimulator blockers (e.g., abatacept);  
anti IL-6R monoclonal antibodies (e.g., tocilizumab); IL-17 antagonists (e.g., 
secukinumab); or any therapeutic agent targeted at reducing tumor necrosis factor (TNF) 
activity (e.g., infliximab, etanercept, adalimumab, golimumab, certolizumab) within the 
3-month period prior to enrollment. 
- Subjects who had treatment with any anti-CD20 agent (e.g., rituximab) within the 9-
month period prior to enrolment  
- Subjects who used any investigational drug within 1 month prior to enrollment or within 
5 half-lives of the investigational agent, whichever is longer. 
- Low dose MTX: Patients on < 30 mg of MTX weekly will be eligible for enrollment 
after a 2-week washout interval before receiving ustekinumab 


 
13 
- Vaccines: Prior to initiating therapy with ustekinumab, patients should be up to date 
with all immunizations appropriate for age as recommended by current immunization 
guidelines. Subjects who received any live virus or bacterial vaccinations other than BCG 
within the 3 months before the first administration of the study agent, or are expected to 
receive any live virus or live bacterial vaccinations during the study, or up to 3 month 
after the last administration of ustekinumab are not eligible. Subjects who received BCG 
vaccines within the 12 months before the first administration of the study agent, or are 
expected to receive BCG vaccines during the study, or up to 12 month after the last 
administration of ustekinumab are also not eligible. Caution is advised when 
administering live vaccines to household contacts of patients receiving ustekinumab 
because of the potential risk for shedding from the household contact and transmission to 
patient. Non-live vaccinations received during a course of ustekinumab may not elicit an 
immune response sufficient to prevent disease. 
 
 Baseline laboratory abnormalities 
- Hemoglobin < 8 gr/dL 
- Platelets < 100/mm3 
- WBC < 3000/mm3 
- Absolute neutrophil count < 2.0 X 109/L (2000/mm3) 
- Absolute lymphocyte count < 0.5 X 109/L (500/mm3) 
- Serum creatinine > 1.4 mg/dL in female subjects and > 1.6 mg/dL in male subjects 
- Total bilirubin > 2 mg/dL 
- ALT or AST > 1.5 X ULN 
- Positive hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibody 
 
c.    Source of subjects and recruitment methods 
The source of patients will be the Massachusetts General Hospital Rheumatology clinic 
and the Massachusetts General Hospital Vasculitis and Glomerulonephritis Center, where 
staff physicians will be aware of this study protocol. Potential candidates will be initially 
approached by their primary provider (subjects’ physician) at these two locations, who 
will review available treatment options, including this protocol. After this step, and if the 


 
14 
subject is interested in participating in this study, either Dr. Unizony or Dr. Stone will go 
over the informed consent process. 
 
 
IV. SUBJECT ENROLLMENT 
Procedures for obtaining informed consent 
 Dr. Unizony or Dr. Stone will review the inform consent with the potential candidates 
 
 The diagnosis of GCA will be confirmed through appropriate evaluations that will 
include comprehensive history, complete physical exam, and review of the medical 
records for prior temporal artery biopsy, inflammatory markers level, and cross 
sectional imaging  (See Section III,  inclusion criteria, diagnosis of GCA) 
 
 Potential treatment approaches, including continued glucocorticoid monotherapy, 
conventional 
DMARDs 
(e.g., 
methotrexate), 
experimental 
biologics 
(e.g., 
tocilizumab), and this investigational protocol, will be discussed. 
 
 Patients will be given at least twenty-four (24) hours to consider their potential 
treatment options.  Adequate time will be permitted for patients to ask questions to 
Dr. Unizony or Dr Stone and to discuss treatment options further with family 
members, primary care providers, or referring physicians.   
 
 
V. STUDY PROCEDURES 
a. Study Overview 
This is a single center, open label study that will assess the efficacy and safety of 
ustekinumab plus standard of care with a taper course of prednisone in 20 patients with 
active GCA. The study will enroll 20 subjects with a diagnosis of either new onset GCA 
or relapsing GCA.  The study will consist of a screening phase (up to 6 weeks), a 
treatment phase (52 weeks) and a safety follow up phase (8 weeks). The primary efficacy 


 
15 
assessment will take place at week 52. The maximum duration of subject participation 
(including screening) is 66 weeks (See table 1. Schedule of events).  
 
b. Study drugs 
Treatment protocol 
All subjects will receive ustekinumab and prednisone  
1) Ustekinumab: 90 mg of ustekinumab will be administered at baseline, week 4, 
week 12, week 20, week 28, week 36 and week 44. Ustekinumab will be 
administered in a subcutaneous (SQ) injection in the rheumatology clinic by the 
physician investigator or other qualified study personnel. Ustekinumab 
interruption or withdrawal will be as per current US product insert (See attached 
ustekinumab package insert). In case of ustekinumab-related toxicities that do 
not warrant the discontinuation of the medication, the dose of ustekinumab 
will be reduced to 45 mg keeping the same dosing intervals (See section VII. 
Risks and discomforts, page 24). 
2) Prednisone: All patients will receive standard of care therapy with prednisone 
tapered according to predefined schedules (See table 2, Prednisone tapers). There 
will be 3 possible initial prednisone doses (60 mg, 40 mg and 20 mg) to fully 
capture the different requirements of prednisone for induction of remission in 
GCA. The initial dose of prednisone will be chosen by the investigators following 
best clinical judgment. The duration of the prednisone taper will be 6 months in 
all cases. A 6 month prednisone taper will allow ustekinumab to fully reach 
steady state pharmacokinetics and pharmacodynamics while patients are still on 
prednisone. Patients who presents with vision-threatening manifestations (e.g., 
amaurosis fugax) will be treated with pulse methylprednisolone (1000 mg/day) 
for up to three doses at the discretion of the physician-investigator before starting 
the study prednisone taper at a dose deemed appropriate by the physician-
investigator. Patients with severe clinical manifestations such as visual symptoms, 
jaw claudication or severe headaches will start the taper at a higher dose (e.g., 40 


 
16 
to 60 mg). Patients with less severe clinical manifestations such as PMR 
symptoms or mild headaches will start the taper at lower dose (e.g., 20 to 40 mg).  
Please note that patients are required to have active disease (see inclusion criteria) 
within 6 weeks of baseline visit in order to be eligible for the study. Patients may 
or may not be on prednisone by the time of the screening visit and there is no 
timeframe for prior prednisone use as far as the criteria of disease activity within 
6 weeks of baseline is met. Most of the relapsing patients and some of the new 
onset patients will be taking some prednisone by the time of the screening. For 
those who are already taking prednisone and demonstrate active disease at 
screening visit, the prednisone dose will be increased to one of the protocol initial 
doses (i.e., 20 mg, 40 mg or 60 mg) in order to control that activity. For those who 
are already taking prednisone and are in remission at screening (because the 
prednisone dose was recently modified to control disease activity), the dose will 
be kept if it is one of the protocol starting doses, and if it is not, modified in order 
to start the study on one of the protocol starting doses.  
3) Escape therapy: Patients who do not achieve the status of clinical remission by 
week 12, can not follow the study prednisone taper, or develop a disease flare 
before week 52 will be deemed failures for the primary endpoint. Those subjects 
will stop ustekinumab and be offered treatment with an investigator-defined 
prednisone rescue regimen 
 
Upon study completion, decisions on treatment options for individual subjects will be at 
the discretion of the investigator. 
 
Concomitant medications:  
- Anti-platelet therapy All the subjects will be treated with aspirin 81 mg daily unless 
contraindicated.  


 
17 
- Glucocorticoid induced osteopenia/osteoporosis prevention and treatment All the 
subjects will receive oral calcium and 25-hydroxy vitamin D supplementation (Ca 1200-
1500 mg and vitamin D 800-1000 IU daily in divided doses).  Bisphosphonate therapy 
(e.g., alendronate 70 mg weekly or zolendronate 5 mg annually) will also be employed at 
the discretion of the physician-investigator for the prevention of glucocorticoid-induced 
osteoporosis. Participants with documented osteoporosis will be treated with FDA-
approved drugs for osteoporosis according to clinical guidelines [e.g., National 
Osteoporosis Foundation (NOF)].  
- Gastric prophylaxis. Prophylaxis with proton pump inhibitors or H-2 blockers will be 
employed at the discretion of the physician-investigator for the prevention of 
glucocorticoid-induced gastrointestinal side effects 
- PCP prophylaxis with an acceptable regimen which may include sulfamethoxazole and 
trimethoprim one single strength pill (80 mg / 400 mg) daily, sulfamethoxazole and 
trimethoprim one double strength pill (160 mg / 800 mg) three times a week or dapsone 
50 to 100 mg daily 
c. Study Visits (See table 1. Schedule of events). 
- Screening visit (-42 to 0 days before Baseline). Complete medical history, physical 
examination and selective laboratory investigations will be obtained for the purpose of 
confirming the diagnosis of active GCA, determining study eligibility, and assessing 
baseline values for the outcomes of interest 
 
During this visit the following procedures will be completed 
 Written Informed Consent 
 Subject Demography  
 Medical and surgical history  
 GCA history evaluation (date of disease diagnosis, date of temporal artery biopsy, 
duration of prednisone treatment, prednisone-related adverse events) 
 Inclusion/Exclusion Criteria  
 Concomitant Medications  
 Assessment of signs and symptoms of GCA/PMR activity 


 
18 
 Vital signs and Physical exam 
 Screening laboratory tests including complete blood count (CBC), creatinine, 
BUN, AST, ALT, total bilirrubin, alkaline phosphatarse, ESR, CRP level, urine 
analysis, HCV antibody, HBV superficial antigen, and HBV anti core antibodies. 
 Chest x-ray (CXR) 
 Electrocardiogram (ECG) 
 Urine or serum pregnancy testing will be completed for female patients who 
report their last menstrual period within 12 months of the screening visit  
 Evaluation for latent TB infection with interferon gamma releasing assay (e.g., 
quantiferon test or T spot). 
 Blood samples for optional research studies (DNA/RNA/flow cytometry/serum 
biomarkers)  
 
 
Following the Screening period, eligible subjects will proceed with a 52-week treatment 
phase 
- Baseline-Week 52 visits 
Subjects will start the treatment phase of the study only if all eligibility criteria are met. 
The treatment phase of the study will consist of a Baseline visit, and subsequent visits at 
week 4, week 12, week 20, week 28, week 36, week 44 and week 52. 
Ustekinumab will be administered in site by the principal investigator or designated 
trained personnel at Baseline, and at visits week 4, week 12, week 20, week 28, week 36, 
and week 44. In addition, the patients will follow a pre-specified prednisone taper  (See 
table 2. Prednisone taper protocol). 
During Baseline through week 52 visit the following procedures will be completed 
 Vital signs and Physical exam 
 Concomitant Medications  
 Adverse Events Assessments 
 Assessment of signs and symptoms of GCA/PMR activity 
 Ability to adhere to the pre-specify prednisone taper 
 Ustekinumab administration (baseline, w4, w12, w20, w28, w36, w44) 


 
19 
 Laboratories (CBC, creatinine, BUN, AST, ALT, total bilirrubin, alkaline 
phosphatarse, ESR, CRP level, and lipid profile) 
 Blood samples for optional research studies (RNA/flow cytometry/serum 
biomarkers)  
 
The main efficacy and safety endpoint will be measured at 52 weeks (See below section 
IV.) 
 
- Safety follow up visit. The participants will undergo a safety follow up visit at week 60 
During the safety follow up the following procedures will be completed 
 Vital signs and Physical exam 
 Concomitant Medications  
 Adverse Events Assessments 
 Assessment of signs and symptoms of GCA/PMR activity 
 Laboratory assessments (CBC, creatinine, BUN, AST, ALT, total bilirrubin, 
alkaline phosphatarse, ESR, and CRP level) 
 Blood samples for optional research studies (RNA/flow cytometry/serum 
biomarkers)  
d.    Toxicity Grading Scale 
All adverse events will be recorded and classified according to the most recent version of 
the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE), published May 28, 2009 
(http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf) 
 
Adverse events will be recorded and graded 1 to 5 according to the CTCAE grades 
provided below: 
Grade 1 = Mild adverse event 
Grade 2 = Moderate adverse event 
Grade 3 = Severe and undesirable adverse event  


 
20 
Grade 4 = Life-threatening or disabling adverse event 
Grade 5 = Death 
e. Optional research studies (DNA, RNA and flow cytometry analyses) 
Optional research samples will be collected from patients who give specific consent to 
participate in this optional research. The Informed Consent Form will contain a separate 
section that addresses participation in the optional research studies 
 
A blood sample will be collected for genetic analysis as follows: Blood (approximately 6 
mL in K3 EDTA) for DNA isolation will be collected as shown table 1 (Schedule of 
events). The sample may be processed using techniques such as array-based hybridization 
or PCR  
Blood samples will be collected for RNA expression analysis as follows: Blood (1 × 
approximately 2.5 mL collected in PAXgene vacutainers) for RNA isolation will be 
obtained as shown in table 1 (Schedule of events). The samples may be tested using 
techniques such as microarray profiling, RNA sequencing, and/or reverse transcriptase − 
polymerase chain reaction (RT-PCR)  
 
Blood samples will be collected for serum assays for biomarkers as follows: Blood (one 
sample of approximately 6.0 mL) for serum isolation will be obtained at various time 
points as shown in table 1. (Schedule of events). The samples may be tested using 
techniques such as ELISA and Luminex. Biomarkers to be determined may include 
cytokines (e.g., IL-17, IFN gamma, IL-12, IL-6, etc), chemokines (e.g., CXCL-9, CXCL-
10, etc), and other soluble molecules (e.g., VGEF) 
 
Blood samples will be collected for determination of cell subpopulations as follows: 
Blood (approximately 15 mL) for peripheral blood mononuclear cell (PBMC) and 
lymphocyte purification and determination of cell subpopulations by flow cytometry will 
be collected as shown table 1 (Schedule of events). Subpopulation of cells to be analyzed 
include T-helper (Th)1 cells, Th17 cells, and regulatory T cells. 
 


 
21 
Optional research samples will be destroyed no later than 15 years after the date of 
informed consent signature. These samples will be de-indentified and stored in the 
Division of Rheumatology, Allergy and Immunology (Dr Andrew Luster’s Laboratory) 
 
Optional research samples will be used to achieve the following objectives: 
- 
To study genetic variants associated with GCA and treatment response to the 
study medication 
- 
To study the association of biomarkers with efficacy, adverse events, or other 
disease-related outcomes 
- 
To increase knowledge and understanding of disease biology 
 
Patients will be told that they are free to refuse to participate in the optional research 
studies, and may withdraw their specimens at any time and for any reason during the 
storage period.  
VI. BIOSTATISTICAL ANALYSIS   
Signs and symptoms of GCA activity, compliance with the prednisone taper, specific 
laboratory parameters (e.g., ESR, CRP) and the occurrence of adverse events will be 
assessed over time for the analysis of the efficacy and safety endpoints. 
Study endpoints 
Primary efficacy endpoint: 
1) Percentage of patients in glucocorticoid-free remission at 52 weeks 
 
The definition of glucocorticoid-free remission contains 3 elements: 
- Absence of clinical signs or symptoms of active GCA and PMR along with the 
normalization of the ESR (<40 mm/hour) and CRP (<10 mg/L) 
- Completion of the pre-specified prednisone taper protocol  
- Absence of disease flare (relapse) since the induction of remission 
 


 
22 
Definition of flare: Re-appearance of unequivocal signs or symptoms of active GCA or 
PMR (with or without elevation of ESR and CRP) that requires increase in the prednisone 
dose in order to be controlled 
 
Secondary efficacy endpoint 
1) Percentage of patients in clinical remission on prednisone ≤ 5 mg/day at 52 weeks  
 
Clinical remission is defined as the absence of clinical signs or symptoms of active GCA 
and PMR along with the normalization of the ESR (<40 mm/hour) and CRP (<10 mg/L) 
regardless of the treatment being received 
2) Time to disease flare 
3) Number of disease flares at 6 and 12 months 
4) Cumulative prednisone dose 
5) ESR and CRP 6 and 12 months 
Safety endpoints 
1) The number, nature and severity of adverse events (AE) at week 52 and 60 
2) The number, nature and severity of serious AE (SAE) at week 52 and 60 
3) Number of glucocorticoid-related adverse events at week 52 and 60 
 
 Statistical Methods  
Continuous data will be summarized using descriptive statistics (e.g., means, standard 
deviations, medians, interquartile ranges).  Categorical data will be summarized as 
numbers and corresponding percentages. Descriptive statistics and two-sided 95% 
confidence intervals will be calculated to assist the interpretation of efficacy outcomes.  
The remission rate of patients treated with Ustekinumab in this study will be compared to 
the remission rate by week 52 of historical controls treated with prednisone monotherapy 
in clinical trials (~15% in Jover et al. MTX trial 2001 [3]; 10% in Hoffman el al. MTX 
trial 2001 [4]; 50% in Hoffman el al. Infliximab trial 2007 [6] [early stop before 52 
weeks due to inefficacy]; 22% in Martinez-Taboada et al. Etanercept trial [8]; 30% in 


 
23 
Seror et al. Adalimumab trial [7]) Setting up the probability of type I error at 0.05 and 
type II error at 0.2, and assuming a 40% remission rate by 52 week in historical controls, 
a sample size of 20 patients will provide more than 80% power to detect a difference in 
the proportion of patients in remission between the ustekinumab group  and the historical 
controls of 30% if that difference actually exists. 
 
We will complete an interim analysis after 5 patients from each stratum (i.e., new onset 
and relapsed disease) have completed 12 months of treatment. In case the flare rate 
within any of the strata is ≥ 60%, that strata will be terminated 
VII. RISKS AND DISCOMFORTS 
With the exception of ustekinumab administration, which is experimental, all the 
procedures performed in this study are consistent with the SOC for a patient with GCA.   
a.   Complications of Subcutaneous Medication Administration 
The injection of subcutaneous medications is associated with a mild degree of discomfort 
at the injection site for a short period of time.  Small degrees of bleeding or bruising may 
occur at the injection site.  Skin irritation (erythema) and rarely cellulitis can result at the 
site of injection.   
 
To minimize this risk, we have experienced infusion nurses who are experts in the 
administration of subcutaneous medications commonly used in the rheumatology practice 
(e.g., etanercept, adalimumab).   
 
b.    Potential Side-effects of Ustekinumab [56] 
Ustekinumab has been approved by the FDA in 2009 for adults with chronic moderate to 
severe plaque psoriasis. Thus, there is substantial clinical experience with this drug and 
the adverse effect profile is well defined. 
 
 Common mild and self-limited side effects include  
- Dizziness 
- Headache 


 
24 
- Back pain 
- Myalgias 
- Injection site erythema 
- Diarrhea 
- Upper airway infection 
 
 Potential serious side effects 
- Infections 
Ustekinumab may increase the risk of infections and reactivation of latent infections. 
Serious bacterial, fungal, and viral infections were observed in subjects receiving 
ustekinumab.  
 
As a risk mitigation strategy, patients will be screened for latent TB infection (LTBI), and 
undergo close monitoring for prompt diagnosis and treatment of any potential infection. 
Patients will be instructed to seek medical advice if signs or symptoms suggestive of an 
infection occur. Ustekinumab will not be given to patients with any clinically important 
active infection. Ustekinumab will not be administered until any clinically important 
active infection resolves or is adequately treated. Should a patient have a serious or 
opportunistic infection, ustekinumab will be discontinued and the patient will not be re-
challenged with the drug. 
 
- Malignancy 
Controlled trials have not shown increased risk of cancer associated with ustekinumab. 
However, given its immunosuppressive effects, surveillance for malignancy is required. 
Appropriate age and gender cancer screening will be recommended as per current 
national guidelines, and patients will be closely monitored during the study. Any sign or 
symptom suggestive of malignancy will be properly investigated. If a neoplastic 
condition were diagnosed, ustekinumab will be discontinued, and patients will be referred 
to oncology (or other pertinent specialist) for appropriate evaluation and treatment. 
 
- Cardiovascular events 


 
25 
Phase 2 psoriasis studies showed an imbalance in the incidence of cardiovascular events, 
which were more frequent in the ustekinumab treated patients. Increased cardiovascular 
morbidity was not confirmed in phase 3 studies.  
 
Sensitivity analysis showed an incidence of serious and non serious cardiovascular AE of 
4.5%, 3.8% and 4.3% in the placebo, ustekinumab 45 mg and ustekinumab 90 mg, 
respectively. The rates of myocardial infarction and stroke seen in clinical trials were 
consistent with or lower than the rates expected in the general population. 
 
The presence of cardiovascular risk factors will not exclude a subject from participating 
in this study.  However, to minimize cardiovascular risks and following the standards of 
our practice, there will be communication with the subjects’ primary care physician to 
have cardiovascular risk factors (e.g., hypertension, dylipidemia, smoking, diabetes) 
addressed according to national guidelines. 
 
- Hypersensitivity reactions 
No anaphylaxis or serum sickness events were reported in clinical trials, but serious 
allergic reactions (including angioedema, dyspnea and hypotension), and hypersensitivity 
reactions (including rash and urticaria) have been reported post-marketing. 
 
Subjects will be monitored for hypersensitivity reactions and treated accordingly. If a 
serious hypersensitivity reaction occurs (e.g., analphylaxis), ustekinumab will be 
discontinued and subjects will not be re-challenged with the drug. 
 
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS) 
RPLS has been rarely reported in patients treated with ustekinumab. If RPLS is suspected 
in patients presentating with headache, seizures, confusion, or visual disturbances, 
ustekinumab will be discontinued, and patients will be properly evaluated and treated. 
- Th-2 related disease exacerbation 


 
26 
No exacerbation of Th2 driven pathologies such as asthma or airway allergies were 
reported during clinical trials. Patients will be monitored for exacerbation of 
hypersensitivity conditions, and treated accordingly if indicated. 
 
- Laboratory abnormalities 
Markedly abnormal changes in hematology and chemistry laboratory values were 
infrequent during clinical trials, with comparable rates among ustekinumab and placebo 
treated patients. The ustekinumab manufacturer does not recommend any type of 
laboratory monitoring during ustekinumab treatment. 
 
Selected labs will be checked at different times during the study (See table 1. Schedule of 
events). If a marked laboratory abnormality is detected (See below section IX.b. Criteria 
for dropping a subject from the study), the study drug will be discontinued and the patient 
will not be re-challenged. 
Ustekinumab dose may be reduced to 45 mg for any of the following reasons: 
1) Recurrent non-serious infections 
2) Other non-serious adverse events deemed to be secondary to ustekinumab that 
justify a dose reduction 
 
VIII POTENTIAL BENEFITS 
a.    Potential benefits to Subjects 
The Subjects may benefit from having their disease controlled more effectively than with 
prednisone monotherapy or prior immunosuppressive regimens. They may also benefit 
from requiring less treatment with prednisone, and thereby incurring in fewer side effects 
associated with this treatment (e.g., hypertension, diabetes, osteoporosis, gastrointestinal 
bleeding, glaucoma, cataracts, other).   
 
b.    Potential benefits to Society 
There is great unmet need for the treatment of GCA. Glucocorticoids are still the main 
agents used to control disease activity and prevent complications. However, 
glucocorticoid treatment is invariably associated with undesirable side effects that impair 
quality of life of patients and increase costs to society. 


 
27 
 
Ustekinumab may prove to be effective in controlling GCA activity and exerting 
glucocorticoid-sparing effects. Therefore, ustekinumab may increase the quality of life of 
the patients, and reduce the costs of treating glucocorticoid -related morbidity. On the 
other hand, ustekinumab may increase the options to treat GCA in patients refractory to 
or unable to take glucocorticoids due to contraindications (uncontrolled hypertension, 
uncontrolled diabetes, severe osteoporosis, cataracts, mood disorders, gastrointestinal 
bleeding), or toxicity.  
 
In randomized controlled trials (mostly including newly diagnosed GCA subjects), the 
flare rate within 12 months in patients only receiving glucocorticoids has been between 
50% and 85% [6-8, 19]. If  ≥ 60% of the subjects in this cohort of GCA patients achieve 
the primary outcome (glucocorticoid-free remission) at 12 months, then this will be 
considered a successful pilot study, and an adequately powered randomized controlled 
trial would be indicated. 
IX. MONITORING AND QUALITY ASSURANCE 
Drs. Unizony and Stone will monitor study data to ensure the safety of patients.   
 
a.    Specific elements related to the safety of study subjects that will be examined 
include: 
 Deaths 
 Hospitalizations from any cause 
 Infections 
 Injection site reactions 
 Other unexpected and serious adverse events 
 
b.    Criteria for dropping a subject from the study 
 A disease flare while on ustekinumab (treatment failure) as defined by the principal 
investigator 
 The occurrence of any malignancy,  
 The occurrence of major cardiovascular event (e.g., stroke, acute coronary syndrome)  


 
28 
 The occurrence of reversible posterior leukoencephalopathy syndrome (RPLS) 
 The occurrence of a severe hypersensitivity reaction, (e.g., anaphylaxis, 
bronchospasm, angioedema) 
 The worsening of any Th2 related pathology (e.g., asthma) 
 The occurrence of a serious, systemic, opportunistic, chronic/recurrent or blood-borne 
infection 
 The occurrence of any marked laboratory abnormality including: Hemoglobin < 8 
gr/dL, Platelets < 100/mm3, WBC < 3000/mm3, Absolute neutrophil count < 2.0 X 
109/L (2000/mm3), Absolute lymphocyte count < 0.5 X 109/L (500/mm3), Serum 
creatinine > 1.4 mg/dL  in female subjects and > 1.6 mg/dL in male subjects, Total 
bilirubin > 2 mg/dL, ALT or AST > 1.5 X ULN 
 
c.    Specific elements of efficacy that will be examined include: 
 Improvement of active GCA symptoms, as judged by medical history, physical 
examination, and laboratory tests (ESR, CRP) 
 Ability to followed the pre-specified glucocorticoid taper  
 Ability of maintain remission off glucocorticoids 
 Glucocorticoid-sparing effects by analyzing the incidence of glucocorticoid-related 
side effects  
 
d.    Adverse event reporting guidelines: 
Adverse events and unanticipated problems involving risks to subjects or others will be 
reported to the PHRC in accordance with PHRC adverse event and unanticipated 
problems reporting guidelines.  
Regarding safety data collection and reporting also refer to Addendum 1 (Interventional 
IIS Janssen Scientific Affairs Requirements for Safety Data Collection and Reporting) 
The investigator may share coded safety information with Janssen Scientific Affairs, LLC so 
it may conduct additional reviews of the coded information in order to study the safety and 
effectiveness of the study drug, to develop a better understanding of disease, or to improve 
the efficiency of future clinical trials. 


 
29 
 
 
 
 
 
 


 
30 
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Immunol 2006, 177(7):4917-4926. 


 
33 
39. 
Leung Y, Panaccione R: Update on ustekinumab for the treatment of Crohn's 
disease. Gastroenterology clinics of North America 2014, 43(3):619-630. 
40. 
Gottlieb A, Menter A, Mendelsohn A, Shen YK, Li S, Guzzo C, Fretzin S, 
Kunynetz R, Kavanaugh A: Ustekinumab, a human interleukin 12/23 
monoclonal antibody, for psoriatic arthritis: randomised, double-blind, 
placebo-controlled, crossover trial. Lancet 2009, 373(9664):633-640. 
41. 
Ritchlin C, Rahman P, Kavanaugh A, McInnes IB, Puig L, Li S, Wang Y, Shen 
YK, Doyle MK, Mendelsohn AM et al: Efficacy and safety of the anti-IL-12/23 
p40 monoclonal antibody, ustekinumab, in patients with active psoriatic 
arthritis despite conventional non-biological and biological anti-tumour 
necrosis factor therapy: 6-month and 1-year results of the phase 3, 
multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 
trial. Annals of the rheumatic diseases 2014, 73(6):990-999. 
42. 
Poddubnyy D, Hermann KG, Callhoff J, Listing J, Sieper J: Ustekinumab for the 
treatment of patients with active ankylosing spondylitis: results of a 28-week, 
prospective, open-label, proof-of-concept study (TOPAS). Annals of the 
rheumatic diseases 2014, 73(5):817-823. 
43. 
Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, Sands BE, 
Hanauer SB, Targan S, Rutgeerts P et al: Ustekinumab induction and 
maintenance therapy in refractory Crohn's disease. The New England journal 
of medicine 2012, 367(16):1519-1528. 
44. 
Espigol-Frigole G, Corbera-Bellalta M, Planas-Rigol E, Lozano E, Segarra M, 
Garcia-Martinez A, Prieto-Gonzalez S, Hernandez-Rodriguez J, Grau JM, 
Rahman MU et al: Increased IL-17A expression in temporal artery lesions is a 
predictor of sustained response to glucocorticoid treatment in patients with 
giant-cell arteritis. Ann Rheum Dis 2012. 
45. 
Samson M, Audia S, Fraszczak J, Trad M, Ornetti P, Lakomy D, Ciudad M, 
Leguy V, Berthier S, Vinit J et al: Th1 and Th17 lymphocytes expressing 
CD161 are implicated in giant cell arteritis and polymyalgia rheumatica 
pathogenesis. Arthritis Rheum 2012, 64(11):3788-3798. 
46. 
Terrier B, Geri G, Chaara W, Allenbach Y, Rosenzwajg M, Costedoat-Chalumeau 
N, Fouret P, Musset L, Benveniste O, Six A et al: Interleukin-21 modulates Th1 
and Th17 responses in giant cell arteritis. Arthritis Rheum 2012, 64(6):2001-
2011. 
47. 
Weyand CM, Hicok KC, Hunder GG, Goronzy JJ: Tissue cytokine patterns in 
patients with polymyalgia rheumatica and giant cell arteritis. Ann Intern Med 
1994, 121(7):484-491. 
48. 
Visvanathan S, Rahman MU, Hoffman GS, Xu S, Garcia-Martinez A, Segarra M, 
Lozano E, Espigol-Frigole G, Hernandez-Rodriguez J, Cid MC: Tissue and 
serum markers of inflammation during the follow-up of patients with giant-
cell arteritis--a prospective longitudinal study. Rheumatology (Oxford) 2011, 
50(11):2061-2070. 
49. 
Weyand CM, Fulbright JW, Hunder GG, Evans JM, Goronzy JJ: Treatment of 
giant cell arteritis: interleukin-6 as a biologic marker of disease activity. 
Arthritis Rheum 2000, 43(5):1041-1048. 


 
34 
50. 
Briefing Document for Ustekinumab (CNTO 1275). Food and Drug 
Administration Dermatologic and Ophthalmologic Drugs Advisory 
Committee. 2008. 
51. 
Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, 
Dooley LT, Gordon KB: Efficacy and safety of ustekinumab, a human 
interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week 
results from a randomised, double-blind, placebo-controlled trial (PHOENIX 
1). Lancet 2008, 371(9625):1665-1674. 
52. 
Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo 
C, Hsu MC, Wang Y, Li S et al: Efficacy and safety of ustekinumab, a human 
interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week 
results from a randomised, double-blind, placebo-controlled trial (PHOENIX 
2). Lancet 2008, 371(9625):1675-1684. 
53. 
Tsai TF, Ho JC, Song M, Szapary P, Guzzo C, Shen YK, Li S, Kim KJ, Kim TY, 
Choi JH et al: Efficacy and safety of ustekinumab for the treatment of 
moderate-to-severe psoriasis: A phase III, randomized, placebo-controlled 
trial in Taiwanese and Korean patients (PEARL). J Dermatol Sci 2011. 
54. 
Scherl EJ, Kumar S, Warren RU: Review of the safety and efficacy of 
ustekinumab. Therap Adv Gastroenterol 2010, 3(5):321-328. 
55. 
Reich K, Langley RG, Lebwohl M, Szapary P, Guzzo C, Yeilding N, Li S, Hsu 
MC, Griffiths CE: Cardiovascular safety of ustekinumab in patients with 
moderate to severe psoriasis: results of integrated analyses of data from 
phase II and III clinical studies. Br J Dermatol 2011, 164(4):862-872. 
56. 
Ustekinumab [package insert]. Janssen Biotech Inc.; 2009. 
http://www.stelarainfo.com/pdf/PrescribingInformation.pdf. 
 
 
 
 
 
 
 
 
 
 
 
 


 
35 
Table 1. Schedule of events 
EVALUATION 
STUDY VISIT (week +/- 5 days) 
Screen 
 (-42 to 
0 days) 
BL 
4 
12 
20 
28 
36 
44 
52 
608,9 
Safety 
FU / 
EW 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
I/E Criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics, 
medical and surgical 
history  
X 
 
 
 
 
 
 
 
 
 
GCA history 
evaluation 1 
X 
 
 
 
 
 
 
 
 
 
AE Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Con Meds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Evaluation for LTBI3  
X 
 
 
 
 
 
 
 
 
 
Ustekinumab 
Administration 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Signs and Symptoms 
of GCA/PMR activity4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ESR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Chemistry5 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
CBC 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Fasting lipid profile6 
 
X 
 
X 
 
X 
 
 
X 
 


 
36 
HBsAg, anti-HBc Ab 
and anti-HCV Ab 
X 
 
 
 
 
 
 
 
 
 
UA 
X 
 
 
 
 
 
 
 
 
 
CXR 
X 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test7 
X 
 
 
 
 
 
 
 
 
 
DNA 
X 
 
 
 
 
 
 
 
 
 
Serum, RNA and Flow 
X 
 
X 
 
X 
 
X 
 
X 
 
 
1. Date of diagnosis, date of temporal artery biopsy, duration of prednisone treatment, initial prednisone dose, prednisone-related adverse 
events.  
2. Complete examination, including assessments of the skin, head, eyes, throat, neck, lungs, heart, abdomen, lymph nodes, and 
musculoskeletal (MSK) system 
3. Tuberculin test (PPD) and/or interferon gamma releasing assay (IGRA) 
4. Temporal artery or scalp tenderness with palpation; unequivocal jaw claudication; visual changes such us transient diplopia, transient 
blurry vision, amaurosis fugax, or new/worsening decrease visual acuity; or unequivocal evidence of active PMR as manifested by 
shoulder and/or pelvic girdle pain and stiffness (e.g. morning stiffness)  
5. Creatinine, BUN, eGFR, AST, ALT, alkaline phosphatase, total bilirubin 
6. Total cholesterol, LDL cholesterol, HDL cholesterol, triglicerides 
7. If last menstrual period within 12 months of screening visit 
8. Week 60 visit will be a safety follow up visit. During this visit, GCA treatment options moving forward will be discussed with the 
subjects. Treatment from this time point will be guided as per best clinical judgment. 
9. In case of early withdrawal, an early withdrawal visit will take place 8 weeks after the last visit before the early withdrawal 
 
BL = baseline; EW = early withdrawal; I/E = inclusion/exclusion; AE = adverse events; Con Meds = concomitant medications; LTBI = 
latent tuberculosis infection;  ESR = erythrocyte sedimentation rate, CRP = C-reactive protein; CBC = complete blood count; HBsAg = 
hepatitis B superficial antigen; anti-HBc Ab = anti Hepatitis B core antibody; anti-HCV Ab = anti Hepatitis C virus antibody; UA = 
urinalysis; CXR = chest x-ray; EKG = electrocardiogram 
 
 


 
37 
Table 2. Prednisone taper protocol 
 
Week 
Initial prednisone dose (*) 
60 mg 
40 mg 
20 mg 
Daily dose 
(mg/day) 
Cumulative 
dose (mg) 
Daily dose 
(mg/day) 
Cumulative 
dose (mg) 
Daily dose 
(mg/day) 
Cumulative 
dose (mg) 
1 
60 
  
40 
  
20 
  
2 
60 
  
40 
  
20 
  
3 
50 
  
30 
  
17.5 
  
4 
40 
1470 
25 
945 
15 
507.5 
5 
30 
  
20 
  
12.5 
  
6 
25 
  
17.5 
  
10 
  
7 
20 
  
17.5 
  
10 
  
8 
17.5 
2117.5 
15 
1435 
9 
798 
9 
17.5 
  
15 
  
8 
  
10 
15 
  
12.5 
  
7 
  
11 
15 
  
12.5 
  
6 
  
12 
12.5 
2537.5 
10 
1785 
6 
987 
13 
12.5 
  
10 
  
5 
  
14 
10 
  
9 
  
5 
  
15 
10 
  
8 
  
4 
  
16 
9 
2828 
7 
2023 
3 
1106 
17 
8 
  
6 
  
3 
  
18 
7 
  
5 
  
3 
  
19 
6 
  
4 
  
2 
  
20 
5 
  
3 
  
2 
  
21 
4 
  
2 
  
2 
  
22 
3 
  
2 
  
1 
  
23 
2 
  
1 
  
1 
  
24 
1 
3080 
1 
2191 
1 
1211 


 
38 
 
(*) Rational for allowing patients to enter the prednisone taper at different initial 
doses. New onset patients usually require doses of prednisone between 40 to 60 mg for 
induction of remission. In contrast, the prednisone dose required for induction of 
remission in patients with relapsed disease is variable. Relapses characterized by cranial 
symptoms (e.g., headaches, jaw claudication, visual manifestations) usually require 
higher prednisone doses (40 to 60 mg). In contrast, a relapse characterized by 
polymyalgia rheumatica (PMR) symptoms, typically responds to lower prednisone doses 
(e.g., 20 mg). In addition, other patient’s comorbidities (e.g., diabetes, hypertension, etc) 
may influence the prednisone dose selection as lower prednisone doses are associated 
with lower prednisone-induced toxicity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
39 
 
Figure 1. IL-12 and IL-17 pathways and proposed mechanism of action of 
ustekinumab in GCA 
 
 
 
 
 
 
 
 
 
 
 
 


 
40 
Addendum 1. Interventional IIS Janssen Scientific Affairs Requirements for 
Safety Data Collection and Reporting 
   
 
1. OVERVIEW 
As the sponsor of the Study, INSTITUTION and PRINCIPAL INVESTIGATOR 
shall be solely responsible for complying, within the required timelines, any safety 
reporting obligation to competent Health Authorities, IRB/ECs and any participating 
(co or sub) investigators, as defined in applicable laws and regulations.  For the 
purposes of this EXHIBIT, safety data includes adverse events, product quality 
complaints (PQCs), and special situations including pregnancies. 
 
The INSTITUTION and PRINCIPAL INVESTIGATOR will provide safety 
information to Janssen Scientific Affairs on adverse events, special situations 
including pregnancies and product quality complaints as defined within this 
EXHIBIT. 
 
2. Management of Safety Data 
This Study has been designated as an interventional study.  As such, all adverse 
events regardless of causality and special situations excluding those from subjects not 
exposed to a Janssen Medicinal Product and product quality complaints with or 
without an adverse event as described in this Exhibit will be reported from the time a 
subject has signed and dated an Informed Consent Form (ICF) until completion of the 
subject’s last study-related procedure (which may include contact for follow-up 
safety).  Serious adverse events will be reported for 30 days after the last dose of 
study drug. 
   
3. Definitions 
3.1. Adverse Event (AE) 
An adverse event is any untoward medical occurrence in a clinical study subject 
administered a medicinal (investigational or non-investigational) product. An adverse 


 
41 
event does not necessarily have a causal relationship with the treatment. An adverse 
event can therefore be any unfavorable and unintended sign (including an abnormal 
finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational or non- investigational) product, whether or not related to that 
medicinal (investigational or non-investigational) product. (Definition per 
International Conference on Harmonisation [ICH]) 
This includes any occurrence that is new in onset or aggravated in severity or 
frequency from the baseline condition, or abnormal results of diagnostic procedures, 
including laboratory test abnormalities. 
 
3.2. Adverse Events of Special Interest  
Adverse events of special interest are events that Janssen Scientific Affairs 
is actively monitoring as a result of a previously identified signal (even if 
non-serious).  The adverse events of special interest for ustekinumab are:  
 
 
 Malignancies  
 Tuberculosis (TB)  
 Serious infections including Opportunistic infections  
 Severe Hypersensitivity reactions (including anaphylactic reactions and 
angioedema) 
 Neurologic 
events 
(eg, 
demyelination, 
progressive 
multifocal 
leukoencephalopathy (PML), facial palsy, reversible leukoencephalopathy 
syndrome (RPLS)) 
 MACE events (Non fatal Stroke, Non fatal MI, CV death)  
 Erythrodermic psoriasis 
 Pustular psoriasis 
 
Adverse Events of Special Interest will be reported on a Serious Adverse Event 
Report Form and be reported to Janssen Scientific Affairs within 24 hours of 
becoming aware of the event. 


 
42 
 
 
3.3. Individual Case Safety Report (ICSR) 
A valid ICSR must contain the four minimum criteria required to meet regulatory 
reporting requirements. 
 an identifiable subject (but not disclosing personal information such as the 
subject’s name, initials or address) 
 an identifiable reporter (investigational site) 
 a Janssen medicinal product 
 an adverse event, outcome, or certain special situations 
 
The minimum information required is: 
 suspected Janssen medicinal product (doses, indication) 
 date of therapy (start and end date, if available) 
 batch or lot number, if available 
 subject details (subject ID and country) 
 gender 
 age at AE onset 
 reporter ID 
 adverse event detail (AE verbatim in English), onset date, relatedness, 
causality, action taken, outcome, (if available) 
 Janssen protocol ID 
 
3.4. Product Quality Complaint (PQC) 
A product quality compliant is defined as any suspicion of a product defect 
related to a potential quality issue during manufacturing, packaging, release 
testing, stability monitoring, dose preparation, storage or distribution of the 
product, or delivery system.  Not all PQCs involve a subject.  Lot and batch 
numbers are of high significance and need to be collected whenever available. 
 
Examples of PQC include but not limited to: 


 
43 
 Functional Problem: e.g., altered delivery rate in a controlled release 
product 
 Physical Defect:  e.g. abnormal odor, broken or crushed tablets/capsules 
 Potential Dosing Device Malfunction: e.g.,  autoinjector button not 
working, needle detaching from syringe 
 Suspected Contamination 
 Suspected Counterfeit 
 
3.5. Serious Adverse Event (SAE) 
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for 
Medicinal Products for Human Use is any untoward medical occurrence that at any 
dose: 
 
 
Results in death 
 
Is life-threatening 
(The subject was at risk of death at the time of the event. It does not refer to 
an event that hypothetically might have caused death if it were more severe.) 
 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 
Results in persistent or significant disability/incapacity 
 
Is a congenital anomaly/birth defect 
 
Is a suspected transmission of any infectious agent via a medicinal product 
 
Is medically important* 
 
*Medical and scientific judgment should be exercised in deciding whether 
expedited reporting is also appropriate in other situations, such as important 
medical events that may not be immediately life threatening or result in death or 
hospitalization but may jeopardize the subject or may require intervention to 
prevent one of the other outcomes listed in the definition above. These should 
usually be considered serious. 
 


 
44 
NOTE: DEATH FOR ANY REASON SHOULD BE REPORTED AS A 
SERIOUS ADVERSE EVENT. 
 
3.5.1.  Hospitalization 
For reports of hospitalization, it is the sign, symptom or diagnosis which led to the 
hospitalization that is the serious event for which details must be provided. 
 
Any event requiring hospitalization or prolongation of hospitalization that occurs 
during the study must be reported as a serious adverse event, except 
hospitalizations for the following: 
 Hospitalizations not intended to treat an acute illness or adverse event 
(e.g., social reasons such as pending placement in long-term care facility) 
 Surgery or procedure planned before entry into the study. [Note: 
Hospitalizations that were planned before the start of data collection and 
where the underlying condition for which the hospitalization was planned 
has not worsened will not be considered serious adverse events. Any 
adverse event that results in a prolongation of the originally planned 
hospitalization is to be reported as a new serious adverse event.] 
 
3.5.2.  Life-Threatening Conditions 
The cause of death of a subject in a study within 30-days of the last dose of 
Stelara (ustekinumab), whether or not the event is expected or associated with the 
study drug, is considered a serious adverse event. 
 
Disease progression should not be recorded as an adverse event or serious adverse 
event term; instead, signs and symptoms of clinical sequelae resulting from 
disease progression/lack of efficacy will be reported if they fulfill the serious 
adverse event definition. 
 
4. Unlisted (Unexpected) Adverse Event/Reference Safety Information 
 


 
45 
An adverse event is considered unlisted if the nature or severity is not consistent 
with the applicable product reference safety information. For a medicinal 
product(s) with a marketing authorization, the expectedness of an adverse event 
will be determined by whether or not it is listed in the applicable product 
information.  
 
For Stelara (ustekinumab), the link to the package insert is:  
http://www.stelarainfo.com/pdf/PrescribingInformation.pdf 
 
5. Special Reporting Situations  
Safety events of interest for a Janssen medicinal product that require expediting 
reporting and/or safety evaluation include, but are not limited to: 
 
Drug exposure during pregnancy (maternal and paternal) 
 
Overdose of a Janssen medicinal product  
 
Exposure to a Janssen medicinal product from breastfeeding  
 Suspected abuse/misuse of a Janssen medicinal product 
 Inadvertent or accidental exposure to a Janssen medicinal product  
 Failure of expected pharmacological action (i.e., lack of effect) of a Janssen 
medicinal product 
 Medication error involving a Janssen medicinal product (with or without 
patient exposure to the Janssen medicinal product, e.g., name confusion) 
 Suspected transmission of any infectious agent via administration of a 
medicinal product 
 Unexpected therapeutic or clinical benefit from use of a Janssen medicinal 
product 
 
These safety events may not meet the definition of an adverse event; however, 
from a Janssen Scientific Affairs perspective, they are treated in the same manner 
as adverse events. Special situations should be recorded on the Adverse Event 
page of the CRF. 
 


 
46 
Any special situation that meets the criteria of a serious adverse event should be 
recorded on a Serious Adverse Event Report Form and be reported to Janssen 
Scientific Affairs within 24 hours of becoming aware of the event. 
 
6. Pregnancy  
The effect of ustekinumab on human sperm, pregnant women, and women making breast 
milk, unborn babies or breast feeding infants is not known. Pregnant women and women 
making breast milk to feed infants cannot participate in this study. Urine and/or blood 
pregnancy tests will be conducted for female participants who are capable of getting 
pregnant. It is very important that men taking part in this study do not get a woman 
pregnant while taking part in this study. 
 
Contraceptive recommendation will be given to all women participants who could 
become pregnant and all men participants who may father a child as follows: 
 During this study and for 4 months after the last dose of study drug, you must use 
proven birth control methods.  
 If you are using a hormone birth control method (such as oral contraception [“the 
pill”], a patch, injections, etc.), you must also use a second method of birth control, 
such as a condom or diaphragm. It is not known if ustekinumab affects the 
effectiveness of hormonal birth control methods. However, ustekinumab may lower 
the concentration/amount of active ingredients of the hormonal birth control methods. 
 If you are planning to donate eggs (ova, oocytes) during the study and for 4 months 
after your last dose of study drug, you must notify your study doctor or healthcare 
team and discuss the associated risks. 
Pregnancies in women participants and pregnancies in partners of male subjects exposed 
to ustekinumab will be reported by the PRINCIPAL INVESTIGATOR within 24 hours 
of their knowledge of the event using the Serious Adverse Event Form.  Depending on 
local legislation this may require prior consent of the partner. Follow-up information 


 
47 
regarding the outcome of the pregnancy and any postnatal sequelae in the infant will be 
required. 
 
7. Maintenance of Safety Information 
All safety data should be maintained in a clinical database in a retrievable format. The 
INSTITUTION and PRINCIPAL INVESTIGATOR shall provide all adverse events, 
both serious and non-serious, in report format. However, in certain circumstances 
more frequent provision of safety data may be necessary, e.g. to fulfill a regulatory 
request, and as such the data shall be made available within a reasonable timeframe at 
Janssen Scientific Affairs’request. 
 
8. Procedures for Reporting Safety Data and Product Quality Complaints (PQCs) 
for Janssen Medicinal Products to the COMPANY 
All adverse events and special situations, whether serious or non-serious, related or 
not related, following exposure to a Janssen medicinal product are to be documented 
by the investigator and recorded in the CRF and in the subject’s source records. 
Investigators must record in the CRF their opinion concerning the relationship of the 
adverse event to a Janssen medicinal product.  
All (serious and non-serious) adverse events reported for a Janssen medicinal product 
should be followed-up in accordance with clinical practice. 
 
8.1. SAEs and Special Reporting Situations 
All serious adverse events that have not resolved by the end of the study, or that 
have not resolved upon discontinuation of the subject's participation in the study, 
must be followed until any of the following occurs: 
 The event resolves 
 The event stabilizes 
 The event returns to baseline, if a baseline value/status is available 
 The event can be attributed to agents other than the study drug or to factors 
unrelated to study conduct 


 
48 
 It becomes unlikely that any additional information can be obtained (subject 
or health care practitioner refusal to provide additional information, lost to 
follow-up after demonstration of due diligence with follow-up efforts) 
 
The INSTITUTION and the PRINCIPAL INVESTIGATOR) will transmit all 
SAEs and special situations following exposure to a Janssen product under study 
in a form provided by Janssen Scientific Affairs in English within 24-hours of 
becoming aware of the event(s). 
 
In the event the study is blinded, the PRINCIPAL INVESTIGATOR will submit 
an unblinded SAE or pregnancy exposure report to Janssen Scientific Affairs. 
 
All follow-up information for serious adverse events that are not resolved at the 
end of the study or by the time of patient withdrawal must be reported directly by 
the PRINCIPAL INVESTIGATOR, within 24 hours becoming aware, to the 
Janssen Scientific Affairs using Janssen Scientific Affairs’Serious Adverse Event 
Report  
 
All available clinical information relevant to the evaluation of a related SAE, 
serious ADR or special situation is required. 
 
 The INSTITUTION and/or PRINCIPAL INVESTIGATOR are responsible 
for ensuring that these cases are complete and if not are promptly followed-
up. A safety report is not considered complete until all clinical details needed 
to interpret the case are received. Reporting of follow-up information should 
follow the same timeline as initial reports. 
 
 Copies of any and all relevant correspondences with regulatory authorities and 
ethics committees regarding any and all serious adverse events, irrespective of 
association with the Janssen Product under study, are to be provided to 


 
49 
Janssen Scientific Affairs within 24 hours of such report or correspondence 
being sent to applicable health authorities. 
 
8.2. Non-Serious AEs 
All non-serious adverse events should be reported to Janssen Scientific Affairs 
according to the timeframe outlined in the Research Funding Agreement section 
entitled Reporting of Data. 
 
8.3. PQC Reporting 
A PQC may have an impact on the safety and efficacy of the product. Timely, 
accurate, and complete reporting and analysis of PQC information from studies 
are crucial for the protection of patients, investigators, and Janssen Scientific 
Affairs, and are mandated by regulatory agencies worldwide. Janssen Scientific 
Affairs has established procedures in conformity with regulatory requirements 
worldwide to ensure appropriate reporting of PQC information. Lot and/or Batch 
#s shall be collected or any reports failure of expected pharmacological action 
(i.e., lack of effect). The product should be quarantined immediately and if 
possible, take a picture. 
 
All initial PQCs involving a Janssen medicinal product under study must be 
reported to Janssen Scientific Affairs by the PRINCIPAL INVESTIGATOR 
within 24 hours after being made aware of the event. The Janssen contact will 
provide additional information/form to be completed. 
 
If the defect for a Janssen medicinal product under study is combined with either 
a serious adverse event or non-serious adverse event, the PRINCIPAL 
INVESTIGATOR must report the PQC to Janssen Scientific Affairs according to 
the serious adverse event reporting timelines.  A sample of the suspected product 
should be maintained for further investigation if requested by Janssen Scientific 
Affairs. 
 


 
50 
9. Reporting Procedures for Reporting Safety Data and Product Quality 
Complaints (PQCs) for Non-Janssen Medicinal Products  
For SAEs, special reporting situations and PQCs following exposure to a non-Janssen 
medicinal product under study, the PRINCIPAL INVESTIGATOR should notify the 
appropriate regulatory/competent authority or the manufacturer of that medicinal 
product (in the absence of appropriate local legislation) as soon as possible. 
 
10. Transmission Methods 
The following methods are acceptable for transmission of safety information to the 
Janssen Scientific Affairs: 
 Electronically via Janssen SECURE Email service (preferred) 
 For business continuity purposes, if SECURE Email is non-functional: 
o Facsimile (fax), receipt of which is evidenced in a successful fax 
transmission report 
 Telephone (if fax is non-functional). 
 
Please use the contact information and process information provided by Janssen 
Scientific Affairs 
 
11. Reconciliation of SAEs 
At a minimum, on a quarterly basis and at the end of the Study, Janssen Scientific 
Affairs will provide to the INSTITUTION and/or PRINCIPAL INVESTIGATOR, a 
listing of all SAEs reported to the Janssen Scientific Affairs.  SPONSOR and/or 
PRINCIPAL INVESTIGATOR will review this listing and provide any discrepancies 
to Janssen Scientific Affairs. 
 
Upon request, INSTITUTION and PRINCIPAL INVESTIGATOR shall provide 
Janssen Scientific Affairs with a summary list of all SAEs, and AEs of Special 
Interest and Special Reporting Situation reports to date, for reconciliation purposes. 
 


 
51 
12. Dissemination of Safety Information from COMPANY to 
INSTITUTION/PRINCIPAL INVESTIGATORS 
PRINCIPAL INVESTIGATOR will be responsible for submitting IND safety reports 
for the Study Product to INSTITUTION’s IRB in accordance with Federal 
regulations 21 CFR 312.66.  The PRINCIPAL INVESTIGATOR will provide a copy 
of each IND safety report to sub-investigators where the study design is either a 
multi-center or cooperative study. 
 
Janssen Scientific Affairs agrees to provide to the PRINCIPAL INVESTIGATOR 
IND safety reports for the Janssen Medicinal Product as they become available until 
all subjects in the Protocol have completed their last Study visit according to the 
Protocol (i.e. Last Subject Last Visit has occurred).  
 
13. Contacting Janssen Scientific Affairs Regarding Safety 
The names (and corresponding contact information) of the individuals who should be 
contacted regarding safety issues will be provided separately by Janssen Scientific 
Affairs. 
 
14. Final Study Report 
The INSTITUTION/PRINCIPAL INVESTIGATOR will prepare a final report 
including a complete and full summary of all adverse events, special situations and 
pregnancy reports according to the timeframe outlined in the pertinent Research 
Funding Agreement section. 
 
 

ICF_001.pdf: 
Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 1 of 30
Subject Identification
Protocol Title: Ustekinumab for the treatment of Giant Cell Arteritis
Principal Investigator: Dr. Sebastian Unizony
Site Principal Investigator:      
Description of Subject Population: Adults with Giant Cell Arteritis (GCA) 
About this consent form
Please read this form carefully.  It tells you important information about a research study.  A 
member of our research team will also talk to you about taking part in this research study.  
People who agree to take part in research studies are called “subjects.”  This term will be used 
throughout this consent form.
Partners HealthCare System is made up of Partners hospitals, health care providers, and 
researchers.  In the rest of this consent form, we refer to the Partners system simply as 
“Partners.”
If you decide to take part in this research study, you must sign this form to show that you want to 
take part.  We will give you a signed copy of this form to keep.
Key Information
Taking part in this research study is up to you.  You can decide not to take part.  If you decide to 
take part now, you can change your mind and drop out later.  Your decision won’t change the 
medical care you get within Partners now or in the future.  
The following key information is to help you decide whether or not to take part in this research 
study.  We have included more details about the research in the Detailed Information section that 
follows the key information.
Why is this research study being done?
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 2 of 30
Subject Identification
In this research study we want to learn whether ustekinumab can help people with giant cell 
arteritis (GCA).
How long will you take part in this research study?
If you decide to join this research study, it will take you about 15 months to complete the study. 
During this time, we will ask you to make 10 visits to MGH Rheumatology Boston or Waltham 
location.
What will happen if you take part in this research study?
If you decide to join this research study, the following things will happen: blood sample 
collection, physical exams, Chest X-ray, and ECG.
Why might you choose to take part in this study?
It is possible that your GCA will improve while you are taking ustekinumab. You may require 
less or even come off prednisone while receiving ustekinumab.
Other patients with GCA may benefit from knowledge gained about the use of ustekinumab to 
treat GCA
Why might you choose NOT to take part in this study?
Taking part in this research study has some risks and requirements that you should consider 
carefully.  
Important risks and possible discomforts to know about include 
•
Infection of the throat or airways or     
sinus
•
Headache
•
Sore throat
•
Dizziness
•
Feeling tired
•
Diarrhea
•
Redness and pain at drug injection site
•
Nausea 
•
back, joint or muscle pain
•
itchiness
•
Vomiting
. 
A detailed description of side effects, risks, and possible discomforts can be found later in this 
consent form in the section called “What are the risks and possible discomforts from being in this 
research study?”.
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 3 of 30
Subject Identification
What other treatments or procedures are available for your condition?
Other treatments or procedures that are available to treat GCA include Actemra and prednisone.
If you have questions or concerns about this research study, whom can 
you call? 
You can call us with your questions or concerns.  Our telephone numbers are listed below.  Ask 
questions as often as you want.  
Dr. Sebastian Unizony is the person in charge of this research study.  You can call him at 617-
726-7938 24/7.  You can also call Ana D Fernandes, M-F 9-5 with questions about this research 
study.If you have questions about the scheduling of appointments or study visits, call the study 
coordinator at 617-724-2792.
If you want to speak with someone not directly involved in this research study, please contact 
the Partners Human Research Committee office.  You can call them at 857-282-1900.
You can talk to them about:

Your rights as a research subject

Your concerns about the research

A complaint about the research

Any pressure to take part in, or to continue in the research study
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 4 of 30
Subject Identification
Detailed Information
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you.  At most, the Web 
site will include a summary of the results.  You can search this Web site at any time.
Why is this research study being done?
We are doing this research study to find out if ustekinumab can help people with giant cell 
arteritis (GCA). We also want to find out if ustekinumab, the study drug, is safe to take without 
causing too many side effects. 
The purpose of this study is to test how well ustekinumab keeps GCA from returning (keeps you 
in remission) once steroids have been stopped. 
The U.S. Food and Drug Administration (FDA) has approved ustekinumab to treat psoriasis. To 
our knowledge, ustekinumab has been used to treat only a few patients with GCA. However, 
ustekinumab is not yet approved for doctors to treat patients with GCA. An investigational use is 
a use that is being tested and is not approved for the treatment of GCA in the United States by 
the U.S. Food and Drug Administration (FDA). 
This study will be used to determine if ustekinumab may be useful in treating patients with GCA. 
ustekinumab acts by blocking chemicals in the body that may cause GCA. This study will also 
look to see if the drug has any important side effects. 
The time interval between ustekinumab administrations used in this study is shorter than the one 
approved for the treatment of psoriasis. The dose of ustekinumab used in this study may be in 
some cases larger than the dose approved for the treatment of psoriasis.
Who will take part in this research?
You have been asked to take part in the study because you have GCA. 
 GCA is a disease that causes inflammation of the body’s largest blood arteries, the aorta and its 
main branches, including the arteries that supply blood to the head and neck regions. 
“Inflammation” is the body’s response to irritation or injury. As these arteries become inflamed, 
symptoms may include headache, fatigue (extreme tiredness), jaw pain and body aches. GCA 
can also result in more serious conditions such as blindness and strokes.   
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 5 of 30
Subject Identification
GCA is usually treated with medications called steroids. These steroids are usually effective but 
may need to be taken at high doses and for a long time. This can sometimes result in side effects 
such as diabetes, high blood pressure, thinning of the bones (osteoporosis), and weight gain.  
Sometimes, reducing the steroids leads to a flare (relapse) of the GCA. 
This is a pilot study. Pilot studies are done on a small group of subjects to learn if a larger study 
would be useful. We are asking you to take part in this research study because you have GCA. 
About 20 subjects will take part in this research study. All of the subjects will be enrolled at the 
Massachusetts General Hospital (MGH).
This study was created and is sponsored by the study doctors at MGH. Janssen Scientific Affairs, 
LLC, is the company providing the study drug and funding for this research study to be done.
What will happen in this research study?
If you choose to take part in this study, we will ask you to sign this consent form before we do 
any study procedures. We encourage you to tell your primary care doctor, as well as your other 
doctors, that you are taking part in this study. We also suggest that you talk about this study with 
your family.
Screening Visit (Visit 1): This visit will take about an hour. You will need to have the following 
check-ups or tests as part of the screening visit to find out if you can be in the study. These tests 
may be done even if you do not join the study. It may take up to 6 weeks or as little as 2 weeks 
before the study doctor has all of the information that he/she needs to determine whether the state 
of your health and your GCA allows you to be in the study. The study doctor will review the 
results of these tests with you. If you don’t qualify for the study, the study doctor will tell you 
why.
This visit will include:

Medical history: You will be asked about your health and any illnesses you may have or 
had in the past including your giant cell arteritis. You will be asked about the medicines 
you are taking including over the counter medicines, vitamins, and herbal treatments.

Physical examination: You will receive a complete physical examination.

Vital signs: Your weight, height, blood pressure, temperature and hear rate will be 
checked.

Determination of the activity of your GCA by the study doctors

Electrocardiogram (ECG): This test will record the electrical activity of your heart.

Blood draw: About 13 teaspoons (about 65 ml) of blood will be drawn from a vein for lab 
tests. Some of this blood will be used to determine if you have other diseases, such as 
hepatitis or tuberculosis. 

A skin test to evaluate prior exposure to tuberculosis may be performed
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 6 of 30
Subject Identification

Urine analysis

Chest X-ray: This test will be done to see if you have any sign of infection such as 
tuberculosis. 

Pregnancy test: If you are a woman and can have children, a blood or urine test will be 
done to see if you are pregnant.

Blood samples for optional GCA research studies 
Vaccines
Vaccines are made to help protect people from certain illnesses. Some vaccines are made from 
live bacteria or live viruses. You cannot receive most kinds of live vaccines (for example, 
FluMist™, varicella) within 3 months of starting this study, during the study, or for 3 months 
after the last study injection. Another kind of live vaccine is BCG, which is a vaccine against 
tuberculosis.  You cannot receive a BCG vaccine during this study or for 12 months after the last 
study injection. You could get sick from these kinds of vaccines while on ustekinumab. If you do 
get a live vaccination during this study, you must tell your study doctor immediately.
Tell your study doctor if anyone living in your home needs a live vaccine.  Some viruses used in 
live vaccines can spread from a close contact (someone living in your home) to people with a 
weakened immune system.
Other kinds of vaccines, like tetanus and flu shots, are allowed. It is not known if ustekinumab 
may interfere with them from working. Tell your study doctor before getting any vaccine while 
you are in this study.  
If you do get a live vaccination during this study, you should tell your study doctor, as you may 
no longer be allowed to receive any more study medication.
Interactions with other medications that you may be taking
Ustekinumab may interact with other medicines. Be sure to tell your study doctor about all the 
medicines and remedies that you take. The medications that are not permitted are:

Methotrexate within 2 weeks of starting ustekinumab

Azathioprine, mycophenolate mofetil, cyclophosphamide, chlorambucil, tacrolimus, 
leflunomide, anakinra, canakinumab, belimumab, abatacept, tocilizumab, infliximab, 
etanercept, adalimumab, golimumab, or certolizumab within 3 months of starting 
ustekinumab

Rituximab within 9 months of starting ustekinumab
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 7 of 30
Subject Identification

Any investigational medication within 1 month prior to starting ustekinumab or within 5 
half-lives (the amount of the drug in the body will be half of the initial starting dose) of 
the investigational medication, whichever is longer. If you have been on an 
investigational medication tell your study doctor about it.
Treatment phase visits (Visits 2-9): These visits will take about half an hour each. Visit 2 will 
take place within 6 weeks of the screening visit. Visits 2 and 3 will take place 4 weeks apart. 
Visits 3 to 9 will take place every 8 weeks.
At these visits we will:

Give you a physical examination

Ask you about side effects or health problems since your last visit

Ask you about all the medications you are taking

Determine whether your GCA is active or in remission

Draw a blood sample to monitor your health during the study

Administer you the study drug ustekinumab

Prescribe you the prednisone tablets and explain you how to reduce the amount of 
prednisone that you take

Draw extra blood samples for optional GCA research studies 
Taking the study drug ustekinumab

In this research study, the study drug ustekinumab will be given by injection under the 
skin of your abdomen (stomach, belly area) or your thigh, using an already filled (pre-
filled) syringe. 

You will receive subcutaneous injections of ustekinumab 90 mg at visits 2, 3, 4, 5, 6, 7, 
and 8. 

The injections will be done by your study doctors or other qualified personnel of the 
study.
Taking prednisone

During the study you will also take prednisone. Prednisone is a steroid drug medication 
that suppresses the immune system and is the usual treatment for giant cell arteritis. 

The prednisone dose will be gradually reduced until the dose is zero. This gradual 
reduction of the prednisone dose is called “taper” or “tapering”

You will start the tapering at a dose required to control your GCA symptoms. The 
starting dose of prednisone will be one that your study doctor decides is most appropriate 
for you and your GCA. The starting dose will be 60 mg, 40 mg, or 20 mg

You will take the prednisone by mouth with a full glass of water and at a meal to prevent 
stomach upset. You should try and take your doses at the same time every day, taking 
care not to miss any. If you skip a dose, take it as soon as you remember. Never take a 
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 8 of 30
Subject Identification
double dose. Do not stop taking prednisone without letting the study doctor know. If you 
stop taking your prednisone abruptly, you could develop symptoms of adrenal 
insufficiency such as abdominal pain, nausea, vomiting, body aches, fatigue and low 
blood pressure.

If at any time your GCA worsens, the study doctor will stop the taper and give you a 
higher dose of prednisone

If your GCA is well controlled during the study, you will take prednisone for 6 months

If your GCA is not well controlled during the study, your study doctor may decide to give 
you prednisone for a longer period of time

If your GCA is not well controlled during the study, your study doctor may decide to 
increase your dose of prednisone 

In case you need higher doses of prednisone or prednisone for a longer period of time, 
your study doctor will tell you why
Concomitant Medications
Your study doctor will require that you also take a medication to prevent a lung infection called 
“PCP” pnemonia. There are few options to prevent this infection including a combination of 
sulfamethoxazole and trimethoprim (also called bactrim) or dapsone. 
Your study doctor may recommend that you also take a baby aspirin to prevent GCA 
complications
Your study doctor may recommend that you also take additional medications to prevent or treat 
prednisone related adverse events. This medication may include calcium and vitamin D 
supplements to treat or prevent osteoporosis (“weak bones”), fosamax or similar medications to 
treat or prevent osteoporosis, and omeprazole or similar medication to treat or prevent acid reflux 
or gastritis.
Safety follow up visits (Visit 10): Eight weeks after visit 9, you will come for the last visit. We 
call this visit safety follow up visit or visit 10.
At these visits we will:

Give you a physical examination

Ask you about side effects or health problems since your last visit

Ask you about all the medications you are taking

Determine whether your GCA is active or in remission

Draw a blood sample to monitor your health during the study
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 9 of 30
Subject Identification
After you complete the study we will refer you back to your own doctor for ongoing medical 
care.
We will not provide you with ustekinumab:

After the study is over, or

If the study has been stopped, or

After your part in the study has ended
Stopping the Study Early
Your participation in the study is voluntary. You may choose to stop taking part of the study at 
any time, without giving a reason. Tell the study staff if you want to stop being in the study. 
Your decision will not affect your medical care now or in the future. It will not affect other 
benefits you receive outside the study
If you decide to stop taking part in the study for any reason, we will ask you to make a final 
study visit 8 weeks after your last visit. 
At this visit, we will:

Give you a physical examination

Ask you about side effects or health problems since your last visit

Ask you about all the medications you are taking

Determine whether your GCA is active or in remission

Draw a blood sample to monitor your health during the study
You may need to leave the study if:

The results of certain tests show that you are not right for this study or for the study drug.

You do not follow study instructions for treatment or follow-up visits.

You get new health problems during the study that might not work well with the study 
set-up.

You get pregnant or decide that you want to become pregnant.

The study doctor thinks it is best for you to stop taking the study drug
New information may become available or known that might affect your choice to stay in the 
study. Such information will be shared and discussed with you. 
This new information might include: 

Safety issues with the study drug

Evidence that the study drug may not work

Another treatment becomes available that may help treat your GCA better.
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 10 of 30
Subject Identification
Janssen Scientific Affairs, LLC (the company providing study drug and funding), the regulatory 
authority, or the study doctor may choose to stop the study at any time. We will give you the 
reason at that time.
If your participation in the study is stopped early, you may be asked to complete end of study 
procedures (such as a final medical examination and laboratory tests) for your own safety.
At this visit, we will:

Give you a physical examination

Ask about any side effects or health problems since your last visit

Draw a blood sample
Leaving the Study
If you decide to leave the study and withdraw your consent, it means you decide that no more 
information about your health can be collected. You and the study doctor will discuss the best 
way to do this. You or others (your Caregiver/Legally authorised representative) may be 
contacted to learn about your well-being. This will be done by visits to the clinic.  Any 
information that can be found in the public may be used for the study, even after you withdraw 
consent.
All the data and samples collected before you left the study will still be used for the study. You 
may ask that your samples be destroyed but any data already collected about your samples will 
be used for the study.
Review of Medical Records from Hospital Admissions or Emergency Department Visits
MGH has an electronic system that lets your study doctors know if you are admitted to a Partners 
Hospital, or if you visit a Partners Hospital Emergency Department for any reason. This alert 
will let the study doctors know why you are there. We want to make sure the study doctors know 
about any possible problems or side affects you experience while you are taking part in the 
study.
Study Information Included in Your Electronic Medical Record
A notation that you are taking part in this research study may be made in your electronic medical 
record.  Information from the research that relates to your general medical care may be included 
in the record (for example, list of allergies, results of standard blood tests done at the hospital 
labs).
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 11 of 30
Subject Identification
Please ask your study doctor if you have any questions about what information will be included 
in your electronic medical record.
What are the risks and possible discomforts from being in this research 
study?
All medications may have side effects. Side effects can be mild to serious and may be different 
from person to person. Everyone taking part in the study will be watched carefully for any side 
effects. In the case those happen, your study doctors may give you drugs to help lessen the side 
effects.
Many side effects go away soon after you stop what is causing them. In some cases, side effects 
can be serious and may be long lasting or may never go away. There is also the rare risk of death. 
You should talk to your study doctor as soon as possible about any side affects you may 
experience while taking part in the study.
The risks, side effects and discomforts that have been reported from clinical studies with 
ustekinumab are explained below. The possible discomforts, side effects, and risks related to 
ustekinumab treatment are not all known.
Potential discomforts, side effects, and risks associated with Ustekinumab
The possible discomforts, side effects and risks related to ustekinumab treatment are not all 
known.  Most side effects are not serious. Some may be serious and may require treatment or 
additional testing.  This section describes how frequently side effects occurred in subjects who 
were treated with Ustekinumab.  In this section, the following terms are used:  
•
Very common:  affects more than 1 user in 10
•
Common:  affects 1 to10 users in 100
•
Uncommon:  affects 1 to 10 users in 1,000
•
Rare:  affects 1 to 10 users in 10,000
Very Common:
•
None 
Common:
•
Infection of the throat or airways or     
sinus
•
Headache
•
Sore throat
•
Redness and pain at drug injection site
•
Nausea 
•
back, joint or muscle pain
•
itchiness
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 12 of 30
Subject Identification
•
Dizziness
•
Feeling tired
•
Diarrhea
•
Vomiting
Uncommon:

Swelling, itching, hardness, bleeding, bruising and irritation where the injection is given.

Shingles (a painful rash)

Depression

Inflammation of tissue under the skin. Signs include warmth, swelling, redness and pain

Nasal congestion

Allergic reactions including rash or raised, itchy bumps

Tooth infections

Acne

Feeling weak

Vaginal yeast infection

Chest infection
Rare:

Serious allergic reactions, which could be life-threatening (including low blood pressure, 
trouble breathing, swollen face, lips, mouth and/or throat)

A form of psoriasis with redness and scaling of a much larger area of your skin or your 
entire body (erythrodermic psoriasis)

In rare cases, symptoms such as cough, shortness of breath, and fever may also be a sign 
of an allergic lung reaction to Ustekinumab
Infections
Ustekinumab is a drug that may change how your body fights infections. Serious infections 
requiring hospitalization for medical observation and /or treatment have been seen in 
ustekinumab studies. Some of these infections have also been life threatening.
Tell your study doctor if you have a new infection, if an infection keeps coming back, or if you 
have any signs of infection such as: 
•
Fever
•
Chills
•
Vomiting  
•
Diarrhea
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 13 of 30
Subject Identification
•
Headache 
•
Coughing 
•
Congestion
•
Chest tightness
•
Shortness of breath 
•
Flu-like symptoms 
•
Nausea
•
Frequency or burning while passing urine 
•
Redness warmth, tenderness or swelling of skin or joint
•
Cold sores
•
New or worsening of pain in any location
•
Weight loss
•
Tiredness 
•
Night sweats  
It is unknown if ustekinumab may stop you from developing a fever if you do have an infection, 
and therefore hide that you have one.
Fungal infections have been reported in subjects taking ustekinumab. Some of these fungal 
infections can be serious and involve internal organs. You should find out from your study 
doctor which fungal infections are common where you live or travel and what symptoms they 
cause. Tell your study doctor and family physician right away if you develop symptoms of such 
illnesses.
Subjects who receive ustekinumab may also be at a greater risk for certain serious infections 
such as tuberculosis. Tell your study doctor if you have ever had tuberculosis or anybody in your 
family has ever had tuberculosis or if you come in contact with someone who has tuberculosis. 
Tell your study doctor if you develop:

A cough that does not go away

Coughing up blood

Shortness of breath

Fever

Night sweats

Weight loss 
You should tell your study doctor if you have a new infection, if an infection keeps coming back, 
or if you have any signs of infection. You will not be eligible for this study if you have a history 
of chronic or recurrent infections or ongoing infections such as recurrent kidney infections, lung 
infections, or an open, draining skin wound or sore.
Your study doctor will test you for hepatitis B, hepatitis C, and tuberculosis (TB). Tell your 
study doctor if you have had any of these conditions. You will not be eligible for this study if 
you are infected with hepatitis B, hepatitis C, or TB either now or in the past. For subjects who 
are not eligible for this study due to hepatitis B, hepatitis C, or TB test results, consultation with 
a physician with expertise in the treatment of those infections is recommended.
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
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Subject Identification
Injection site reactions 
Ustekinumab will be given as an injection under your skin. After the injection, temporary and 
common reactions seen at the injection site could include: 

Redness

Pain

Itching

Swelling
Allergic reactions
Ustekinumab may cause an allergic reaction in some people. These reactions are usually mild to 
moderate.  The following can be symptoms of an allergic reaction: 
•
Fever 
•
Chills 
•
Hives
•
Rash
•
Headache
•
Nausea 
•
Flushing 
•
Light-headedness
•
Shakiness 
•
Irregular heartbeats 
•
Chest tightness 
•
Shortness of breath
•
Wheezing        
•
Difficulty in swallowing or breathing
•
Low blood pressure
•
Anaphylaxis (life threatening allergic reaction)   
Serious allergic reactions have been reported in subjects taking ustekinumab and can be life 
threatening.   Signs of a serious allergic reaction include skin rash, swollen face, mouth, lips, 
and/or throat, and trouble breathing.  Tell your doctor or get emergency medical help right away 
if you have an allergic reaction. If you are having trouble breathing, call 911 immediately. If you 
experience a serious reaction to an injection, you will not receive any more study treatments.
If you have an allergic reaction at the doctor’s office, additional necessary treatment will be 
provided immediately.  Your study doctor may give you an antihistamine (medication used to 
treat allergic symptoms such as hay fever) or other medications used for treating an allergy. 
Antihistamines can make you sleepy, so please use caution when driving a car or operating 
machinery. 
Another type of allergic reaction has occurred in some subjects 1-14 days after receiving similar 
medications. The symptoms of this type of allergic reaction may include fever, rash, muscle 
aches and joint pain
Antibodies to ustekinumab
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
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IRB Amendment No: N/A
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Subject Identification
Sometimes the body can make special antibodies that may increase the risk of an allergic 
reaction to either ustekinumab or other antibody medicines. If you have an allergic reaction, you 
may not be able to have these types of medications in the future. You should always tell your 
doctors that you have been treated with human antibodies in this study.
Cancer
Cancers have been reported in subjects who have received ustekinumab, but it is unknown 
whether taking ustekinumab has increased their risk for developing cancer.  Because 
ustekinumab may suppress your immune system, it is possible that it may increase your risk of 
developing cancer, including skin cancers.  It is known that people who have had inflammatory 
diseases (such as, Crohn’s disease, Rheumatoid Arthritis, Ulcerative Colitis etc.) for a long time 
and who use immunosuppressive therapies (such as, azathioprine, methotrexate etc.) for a long 
time have a higher risk of developing cancer. These people get cancer of the lymph nodes more 
often than other people.
Latex allergy 
The needle cover for the prefilled syringe that contains study drug contains dry natural rubber (a 
form of latex). This may cause allergic reactions in people who are sensitive to latex.  Please tell 
your study doctor if you have ever had an allergic reaction to latex.
Cardiac and vascular
Heart attacks and strokes have been reported in subjects who have received ustekinumab.  These 
events have rarely resulted in death.  It is unknown whether taking ustekinumab increases your 
risk for developing these events.  
People, who have psoriasis, and certain other inflammatory diseases, have a higher risk of having 
heart attacks.  These people have heart attacks more often than other people.  Seek medical care 
immediately if you develop; 
 
•
Chest pain or discomfort, 
•
Trouble breathing,
•
Irregular heartbeats, 
•
Dizziness, 
•
Loss of balance, 
•
New numbness or weakness, 
•
Visual or speech changes 
Other therapies
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
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Subject Identification
Tell your doctor if you are receiving treatments that weaken the immune system while using 
ustekinumab.  These treatment combinations have not each been studied with Ustekinumab, so it 
is unknown if they could possibly increase the risk of diseases related to a weakened immune 
system.
Allergy immunotherapy (Allergy Injections)  
 
Tell your study doctor if you have ever had or are now getting allergy injections.  Ustekinumab 
may affect your response to allergy injections.
Reversible posterior leukoencephalopathy syndrome
A single case of a very rare disease of the brain, known as RPLS (reversible posterior 
leukoencephalopathy syndrome), has been reported in a clinical study with ustekinumab. RPLS 
is generally reversible and is not caused by an infection.  Symptoms of this condition are:
•
Headache
•
Seizures
•
Confusion
•
Loss of eyesight
Tell your study doctor if you experience any of these symptoms.
Other risks associated with ustekinumab
Any risks of ustekinumab that relate specifically to the treatment of GCA are unknown. Your 
doctor will closely monitor the activity of your GCA during the trial in order to change your 
treatment should any serious worsening of your condition occur. If you have any problems, you 
should let your study doctor know right away.
Risks of Prednisone
Common side effects: 

Nausea

Vomiting 

Loss of appetite 

Heartburn
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
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Subject Identification

Trouble sleeping 

Increased sweating 

Acne 
Less common side effects:

Muscle pain/cramps 

Irregular heartbeat 

Weakness

Swelling of the hands/ankles/feet 

Unusual weight gain

Signs of infection (such as fever or sore throat that doesn’t go away)

Vision problems (such as blurred vision)

Vomit that looks like coffee grounds 

Black bloody stools

Severe stomach/abdominal pain

Mental/mood changes (such as depression and mood swings)

Slow wound healing

Thinning skin

Menstrual period changes 

Puffy face

Easy bruising/bleeding

Decreased bone density (“weak bones”) and increased risk of fracture
Another less common side effect is that your blood sugar level may rise, which can 
worsen/cause diabetes. Tell your study doctor if you experience symptoms such as increased 
thirst and increased urination.
If you experience any of the above, or have any questions or concerns, please discuss this with 
Dr. Unizony or the study staff.
Concomitant Medication Risks
The possible discomforts, side effects and risks related to sulfamethoxazole and trimethoprim 
may include nausea, vomiting, diarrhea, stomach upset, headache, reduction in your blood cell 
counts (red blood cells, white blood cells, platelets), dizziness, and allergic reactions including 
serious ones such as anaphylaxis (life threatening allergic reaction) and Steven’s Johnson’s 
syndrome. 
The possible discomforts, side effects and risks related to dapsone may include nausea, vomiting, 
diarrhea, stomach upset, headache, reduction in your blood cell counts (red blood cells, white 
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
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Subject Identification
blood cells, platelets), liver function test abnormalities, and allergic reactions including serious 
ones such as anaphylaxis (life threatening allergic reaction) and Steven’s Johnson’s syndrome. 
The possible discomforts, side effects and risks related to baby aspirin may include stomach 
upset, stomach and intestinal ulcers, gastrointestinal bleeding, dizziness, kidney function 
problems, and allergic reactions including serious ones such as angioedema (throat swelling), 
asthma and anaphylaxis (life threatening allergic reaction)
The possible discomforts, side effects and risks related to calcium and vitamin D supplements 
may include stomach upset, nausea, constipation, and increase levels of calcium in your blood
The possible discomforts, side effects and risks related to fosamax or similar medications may 
include stomach upset, esophageal ulcers and perforations, diarrhea, joint pain, allergic reactions, 
osteonecrosis of the jaw (a lesion in the jaw bone), and with prolonged use fractures of the femur 
(the thigh bone).
The possible discomforts, side effects and risks related to omeprazole or similar medications 
include stomach upset, diarrhea, headache, vitamin B 12 deficiency (with prolonged use), 
inflammation of the pancreas, and allergic reactions including serious ones such as anaphylaxis 
(life threatening allergic reaction) and Steven’s Johnson’s syndrome. 
Risks of Stopping Current Medications
When you stop taking certain medications that you were taking for GCA (e.g. prednisone), your 
symptoms or disease might get worse. If this happens, tell the study doctor.
Blood Draws: Drawing blood may cause pain where the needle is inserted. There is a small risk 
of bruising or infection at the place where the needle is inserted. Some people experience 
dizziness, upset stomach, or fainting when their blood is drawn. 
Hepatitis testing: As part of this research study, we will test your blood for hepatitis. For most 
studies, this means that results will become part of your hospital medical record. If these tests 
show that you have hepatitis, you cannot be in the study. We will refer you for medical care if 
we find you have this infection. By law, healthcare providers must report positive test results for 
infectious diseases to public health authorities, including the Massachusetts Department of 
Public Health. These reports are required to identify you by name.
Tuberculosis (TB) testing: As part of this study, we will do a blood test or a skin test for past 
exposure to TB. For most studies, this means that test results will become part of your hospital 
medical record. If this test shows that you have been exposed in the past to TB, you cannot be in 
the study. If needed, we will refer you for medical care. By law, healthcare providers must report 
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
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Subject Identification
positive test results for past exposure to TB to public health authorities, including the 
Massachusetts Department of Public Health. These reports are required to identify you by name
The skin test to assess prior exposure to TB is given under the skin with a small needle. You may 
have mild pain, bleeding, a change in skin color or bruising, and/or an infection where you were 
tested. You will need to return to the study center or visit a qualified medical professional 48 to 
72 hours after the injection for proper evaluation of the test site. If you have a positive skin test, 
you may have mild pain, itching, redness and slight swelling at the site of the skin test.” 
Preventative Medicine for Tuberculosis Infection: Sometimes these medicines have side effects. 
Side effects may include nausea, vomiting, abdominal pain, hepatitis and possibly other 
events.  Your study doctor will provide you with more information on tuberculosis preventative 
treatment.
Risk of X-Rays: As a result of your participation in this study you will be exposed to radiation 
from an x-ray of your chest. Please note that this radiation is not necessary for your medical care 
and is for research purposes only.
The total amount of radiation exposure you will receive from participation in this study is equal 
to a whole body exposure of approximately 0.06 milliSieverts (mSv). A milliSievert is a unit of 
radiation dose. This amount of radiation is about the same as you would normally receive in 1 
week from natural background sources from the earth and the sky.
Scientists disagree on whether radiation doses at these low levels are harmful. A possible effect 
that could occur at doses associated with this study is a slight increase in the risk of developing 
cancer later in life.
ECG: The ECG test is a recording of the electrical activity of your heart. There are no risks 
associated with this test. The sticky pads used may cause slight irritation when they are removed.   
If the hair under the patches needs to be shaved, irritation from shaving also could occur. 
Are there any reproductive risks?
The effect of ustekinumab on human sperm, pregnant women, and women making breast milk, 
unborn babies or breast feeding infants is not known. Pregnant women and women making breast 
milk to feed infants cannot participate in this study.  Urine and/or blood pregnancy tests will be 
conducted for female participants who are capable of getting pregnant.
It is very important that women, while taking part in this study, do not become pregnant. Your 
study doctor will discuss effective birth control methods with you. It is very important that men 
taking part in this study do not get a woman pregnant while taking part in this study.
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
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Subject Identification
For women who could become pregnant or men who may father a child:

During this study and for 4 months after the last dose of study drug, you must use proven 
birth control methods. 

If you are using a hormone birth control method (such as oral contraception [“the pill”], a 
patch, injections, etc.), you must also use a second method of birth control, such as a 
condom or diaphragm. It is not known if Ustekinumab affects the effectiveness of 
hormonal birth control methods. However, Ustekinumab may lower the 
concentration/amount of active ingredients of the hormonal birth control methods.

If you are planning to donate eggs (ova, oocytes) during the study and for 4 months after 
your last dose of study drug, you must notify your study doctor or healthcare team and 
discuss the associated risks.

If you think that you have become pregnant or may have fathered a child while taking 
part in the study, tell your study doctor immediately. 

You should also notify your childbirth doctor that the mother/father received an 
experimental drug (ustekinumab).  

If you are a female study subject and you become pregnant during your participation in 
this study, your treatment with study drug will be stopped and you may be withdrawn 
from some of the study procedures but not from follow-up by your study doctor.  The 
study doctor will ask for your permission to stay in contact with you throughout the 
length of the pregnancy.

If you are a male study subject, and you father a child during your participation in this 
study, the study doctor will ask for your partner’s permission to stay in contact with her 
throughout the length of the pregnancy.
Optional (Not Required) Sub-Studies
                 The following 2 sub-studies are optional, which means they are not required. You can decide 
you don’t want to take part in one or more of them and still be in the main study. Your decision 
will not affect you taking part in the main study or your medical care.
1. Genetic Testing on Your Samples 
This section describes the genetics part of the study. Joining this part of the study is 
optional. You can choose not to join the Genetic study and still take part in the main 
study. 
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
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The purpose of the genetics part of this study is to help scientists to understand GCA and related 
conditions and response to study medicines.  
We get our genes (DNA) from our parents. Different genes may affect who gets GCA or how a 
body reacts to a drug. Scientists look for differences in people’s genes (DNA) that might explain 
this. Genetic research may include the study of certain genes or all your genes also called your 
whole genome. This may include genes involved in the way the drug works (both good and bad) 
or how the drug is broken down in the body. It may also include genes linked to GCA or related 
conditions.
If you choose to take part in the genetics study, we will draw an additional 1½ teaspoons (about 
6 ml) of your blood. If there is a problem looking at your blood sample, we may ask to take the 
sample again. The risks associated with giving a genetics blood sample are the same as the risks 
for giving any blood sample in this study.  
Your sample may be used during the study or in the future to get genetic data. Your sample will 
be stored and used as described in the section “What happens to my blood sample?”
Your genetic data may be:

Studied during the clinical study or in the future.

Studied with the medical information and results from the main study. 

Stored and used as described in the section on “What happens to my personal and 
medical information?” 
You can stop the main study and still participate in the genetic research study. 
If you choose to stop the genetics part of the study after giving a sample, we will not conduct any 
new tests on the sample. We will destroy the sample. If we have gotten genetic data but we have 
not studied that data at the time you stop the genetics part of the study, your genetic data will not 
be used for any purpose in the future. The study doctors will use any results they have from 
studying the data before you stopped participating in the genetics study. 
Please indicate below, by checking “Yes” or “No” and including your signature, whether you 
agree or disagree to allow genetic testing of your samples as described above.
_________YES
__________NO
_____________________ Signature
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
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2. Biomarker Research
This section describes a type of research called biomarker research on GCA. Joining this part of 
the study is optional. You can choose not to join the biomarker research and still take part in the 
main study. 
The purpose of the biomarker research is to better understand how GCA works and how changes 
in your body may relate to when your GCA is better or worse. We may also do additional genetic 
tests on these samples (similar to those described in the genetics part of the study) to further 
understand GCA.
If you choose to take part in the biomarker research portion of the study, we will collect 
additional blood samples from you 5 times during the study for a total of an additional 30 
teaspoons of blood (150ml). The risks associated with giving a blood sample for the biomarker 
research are the same as the risks for giving any blood sample in this study.  
If you withdraw from the biomarker part of the study you may ask that your Biomarker samples 
be destroyed. Any data already collected about your samples will be used for the study. The 
study doctors will use any results they have from studying the data before you stopped 
participating in the biomarker study.
Your sample may be used during the study or in the future to get biomarker data. 
Please indicate below, by checking “Yes” or “No” and including your signature, whether you 
agree or disagree to allow the storage of your samples as described above.
_________YES
__________NO
_____________________ Signature
Genetic Testing
Genetics information that results from this study does not have medical or treatment importance 
at this time. However, there is a risk that information about taking part in a genetic study may 
influence insurance companies or employers regarding your health. To further safeguard your 
privacy, genetic information that we get in this study will not be placed in your medical record.
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it 
illegal for health insurance companies, group health plans, and most employers to discriminate 
against you based on your genetic information. This law will protect you in the following ways: 
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
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• Health insurance companies and group health plans may not request your genetic information 
that we get from this research. 
• Health insurance companies and group health plans may not use your genetic information that 
we get from this research when making decisions regarding your eligibility or premiums. 
• Employers with 15 or more employees may not use your genetic information that we get from 
this research when making a decision to hire, promote, or fire you or when setting the terms of 
your employment. 
Be aware that this federal law does not protect you against genetic discrimination by companies 
that sell life insurance, disability insurance, or long-term care insurance, nor does it protect you 
against genetic discrimination by all employers.
Taking part in a genetic study may also have a negative impact on family or other relationships.  
If you do not share information about taking part in this study, you will reduce this risk.
What happens to my data (personal and medical information)?
It is very important that your personal and medical information stay confidential and secure. The 
study personnel will protect your information in accordance with current law. When you sign 
this consent form you agree that the study doctors and other study personnel can use your 
personal and medical information as described here:

Your study information will be labelled with a code number (for example, 1234782). It will 
not include your name or address. The study doctor will have the link between your name 
and the code number.

The link between your name and the code number will not be shared.  

The study doctors will use your coded information for research only. This may include 
research looking at improving the quality and efficiency in conducting clinical research trials 
in general.
The study doctors may:

Keep your coded information electronically and analyse it by computer to find out what the 
study is telling us. 

Share the coded information with regulatory agencies that approve new medicines,

Share the coded information with people who check that the study is done properly (like the 
ethics committee or review boards),
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
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
Combine the coded information with results from other studies to learn more about the 
medicine and other medicines, and GCA and other diseases and conditions. This may help us 
to assess the risks and benefits of ustekinumab, or to improve disease understanding, 

Publish study results for medical journals, meetings and on the internet for other researchers 
to use; your name will not appear in any publication

Share coded safety information with Janssen Scientific Affairs, LLC (the company providing study 
drug and funding) so it may conduct additional reviews of the coded information in order to study 
the safety and effectiveness of the study drug, to develop a better understanding of disease, or to 
improve the efficiency of future clinical trials
What happens to my blood samples?
If you take part in this study, you will be asked to give blood samples to monitor your health 
during the study. These samples will be destroyed after the tests are done.
You will also be asked to give optional research blood samples if you choose to participate in the 
biomarker research part of the study and a single blood sample if you choose to participate in the 
genetics part of the study. Similar to information collected in the study, your optional researches 
samples may also be used by the study doctor to better understand GCA or to further develop the 
study drug. Your optional research blood samples will be given the same code as your other 
study information and kept in locked storage. Anyone who works with your samples will hold 
the information and results in confidence. Your study doctors may store your optional research 
blood samples for up to 15 years after the end of the study after which time your samples will be 
destroyed. 
What are the possible benefits from being in this research study?
It is possible that your GCA will improve while you are taking ustekinumab. You may require 
less or even come off prednisone while receiving ustekinumab.
Other patients with GCA may benefit from knowledge gained about the use of ustekinumab to 
treat GCA
How may we use and share your samples and health information for other 
research?
The samples and information we collect in this study may help advance other research. If you 
join this study, we may remove all information that identifies you (for example your name, 
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
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Subject Identification
medical record number, and date of birth) and use these de-identified samples and data in other 
research. It won’t be possible to link the information or samples back to you.  Information and/or 
samples may be shared with investigators at our hospitals, at other academic institutions or at 
for-profit, commercial entities.  You will not be asked to provide additional informed consent for 
these uses.
Will you get the results of this research study?
No.  The research study we are doing is only a stepping stone in understanding GCA. Therefore, 
no information about the results of this research study or the results of your individual 
participation in the research study will be given to you or your doctor.  Tests done for the 
research using your samples will not be useful in directing your medical treatment.  The results 
of the tests will not be placed in your medical record.   
What other treatments or procedures are available for your condition?
You do not have to take part in this research study to be treated for your GCA. You may choose 
to continue to get regular care from your own doctor. Most people with this condition are treated 
with long courses of prednisone. If you currently take steroids for your GCA you may wish to 
continue to do so. There have been mixed results using other medications for treatment of these 
disorders (e.g., methotrexate). Alternately you might to decide to:

Take part in another study  

Get no treatment at this time.
Talk with the study doctor, or your family doctor, about your treatment choices.
Can you still get medical care within Partners if you don’t take part in 
this research study, or if you stop taking part? 
Yes.  Your decision won’t change the medical care you get within Partners now or in the future.  
There will be no penalty, and you won’t lose any benefits you receive now or have a right to 
receive.
We will tell you if we learn new information that could make you change your mind about taking 
part in this research study.
What should you do if you want to stop taking part in the study?
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 26 of 30
Subject Identification
If you take part in this research study, and want to drop out, you should tell us.  We will make 
sure that you stop the study safely.  We will also talk to you about follow-up care, if needed.
Also, it is possible that we will have to ask you to drop out of the study before you finish it.  If 
this happens, we will tell you why.  We will also help arrange other care for you, if needed.
Will you be paid to take part in this research study?
We will reimburse you for the cost of travelling to your study visits. You may receive up to 
$50.00 per study visit. We will pay you $500.00 if you complete the study. You will only be 
reimbursed for the visits you complete.
We may use your samples and information to develop a new product or medical test to be sold.   
The Sponsor, hospital, and researchers may benefit if this happens.  There are no plans to pay 
you if your samples are used for this purpose.  
What will you have to pay for if you take part in this research study?
Study funds will pay for certain study-related items and services.  We may bill your health 
insurer for, among other things, routine items and services you would have received even if you 
did not take part in the research.  You will be responsible for payment of any deductibles and co-
payments required by your insurer for this routine care or other billed care.  If you have any 
questions about costs to you that may result from taking part in the research, please speak with 
the study doctors and study staff.  If necessary, we will arrange for you to speak with someone in 
Patient Financial Services about these costs.
What happens if you are injured as a result of taking part in this 
research study?
We will offer you the care needed to treat any injury that directly results from taking part in this 
research study.  We reserve the right to bill your insurance company or other third parties, if 
appropriate, for the care you get for the injury.  We will try to have these costs paid for, but you 
may be responsible for some of them.  For example, if the care is billed to your insurer, you will 
be responsible for payment of any deductibles and co-payments required by your insurer.
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 27 of 30
Subject Identification
Injuries sometimes happen in research even when no one is at fault.  There are no plans to pay 
you or give you other compensation for an injury, should one occur.  However, you are not 
giving up any of your legal rights by signing this form.
If you think you have been injured or have experienced a medical problem as a result of taking 
part in this research study, tell the person in charge of this study as soon as possible.  The 
researcher's name and phone number are listed in the beginning of this consent form.
If you take part in this research study, how will we protect my privacy?
Federal law requires Partners to protect the privacy of health information and related information 
that identifies you.  We refer to this information as “identifiable information.”
In this study, we may collect identifiable information about you from:

Past, present, and future medical records

Research procedures, including research office visits, tests, interviews, and 
questionnaires
Who may see, use, and share your identifiable information and why they may need 
to do so:

Partners researchers and staff involved in this study

The sponsor(s) of this study, and people or groups it hires to help perform this research or 
to audit the research

Other researchers and medical centers that are part of this study

The Partners ethics board or an ethics board outside Partners that oversees this research

A group that oversees the data (study information) and safety of the study

Non-research staff within Partners who need identifiable information to do their jobs, 
such as for treatment, payment (billing), or hospital operations (such as assessing the 
quality of care or research)

People or groups that we hire to do certain work for us, such as data storage companies, 
accreditors, insurers, and lawyers

Federal agencies (such as the U.S. Department of Health and Human Services (DHHS) 
and agencies within DHHS like the Food and Drug Administration, the National 
Institutes of Health, and the Office for Human Research Protections), state agencies, and 
foreign government bodies that oversee, evaluate, and audit research, which may include 
inspection of your records
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 28 of 30
Subject Identification

Public health and safety authorities, if we learn information that could mean harm to you 
or others (such as to make required reports about communicable diseases or about child 
or elder abuse)

Other:       
Some people or groups who get your identifiable information might not have to follow the same 
privacy rules that we follow and might use or share your identifiable information without your 
permission in ways that are not described in this form.  For example, we understand that the 
sponsor of this study may use your identifiable information to perform additional research on 
various products or conditions, to obtain regulatory approval of its products, to propose new 
products, and to oversee and improve its products’ performance.  We share your identifiable 
information only when we must, and we ask anyone who receives it from us to take measures to 
protect your privacy.  The sponsor has agreed that it will not contact you without your 
permission and will not use or share your identifiable information for any mailing or marketing 
list.  However, once your information is shared outside Partners, we cannot control all the ways 
that others use or share it and cannot promise that it will remain private.
Because research is an ongoing process, we cannot give you an exact date when we will either 
destroy or stop using or sharing your health information.  Your permission to use and share your 
identifiable information does not expire.
The results of this research study may be published in a medical book or journal, or used to teach 
others.  However, your name or other identifying information will not be used for these purposes 
without your specific permission.
Your Privacy Rights
You have the right not to sign this form that allows us to use and share your health information 
for research; however, if you don’t sign it, you can’t take part in this research study.
You have the right to withdraw your permission for us to use or share your health information 
for this research study.  If you want to withdraw your permission, you must notify the person in 
charge of this research study in writing.  Once permission is withdrawn, you cannot continue to 
take part in the study.
If you withdraw your permission, we will not be able to take back information that has already 
been used or shared with others, and such information may continue to be used for certain 
purposes, such as to comply with the law or maintain the reliability of the study.
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 29 of 30
Subject Identification
You have the right to see and get a copy of your health information that is used or shared for 
treatment or for payment.  To ask for this information, please contact the person in charge of this 
research study.  You may only get such information after the research is finished.
Informed Consent and Authorization
Statement of Person Giving Informed Consent and Authorization

I have read this consent form.

This research study has been explained to me, including risks and possible benefits (if 
any), other possible treatments or procedures, and other important things about the study.

I have had the opportunity to ask questions.

I understand the information given to me.
Signature of Subject:
I give my consent to take part in this research study and agree to allow my health information to 
be used and shared as described above.
Subject
Date
Time 
Signature of Study Doctor or Person Obtaining Consent:
Statement of Study Doctor or Person Obtaining Consent

I have explained the research to the study subject.

I have answered all questions about this research study to the best of my 
ability.
Study Doctor or Person Obtaining Consent
Date
Time 
Consent of Non-English-Speaking Subjects Using the “Short Form” in the 
Subject’s Spoken Language
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A


Partners HealthCare System
Research Consent Form
General Template - Drug Clinical Trial
Version Date:  January 2019
Page 30 of 30
Subject Identification
Statement of Hospital Medical Interpreter
As someone who understands both English and the language spoken by the subject, I interpreted, 
in the subject's language, the researcher's presentation of the English consent form.  The subject 
was given the opportunity to ask questions.
Hospital Medical Interpreter
Date
Time 
OR
Statement of Other Individual (Non-Interpreter)
As someone who understands both English and the language spoken by the subject, I represent 
that the English version of the consent form was presented orally to the subject in the subject’s 
own language, and that the subject was given the opportunity to ask questions.
Name
Date
Time 
Consent Form Version:  June 14, 2019
Consent Form Title: Unizony_ICF_stelara_clean_Jun19
IRB Protocol No: 2016P000932
Sponsor Protocol No: 2: 17 May 2018
Consent Form Valid Date: 6/19/2019
IRB Amendment No: N/A
Sponsor Amendment No: N/A
Consent Form Expiration Date: 6/27/2020
IRB Amendment Approval Date: N/A