NCT02052596.

Methods	Study design: phase 3, open‐label RCT Duration: February 2014 to April 2016
Participants	Inclusion criteria Setting: outpatient Country: USA Number: 830 participants; treatment (N = 412), control (N = 418) Participants' health status: healthy participants, females of non‐childbearing potential Age: mean 63.3 years Sex: 53.9% female Other relevant information: aged ≥ 50 years 86.9% Caucasian (understood to be white) Exclusion criteria Participants were excluded if "use of any investigational or non‐registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period; chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune‐modifying drugs within six months prior to the first vaccine dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent). A prednisone dose of < 20 mg/day is allowed. Inhaled, topical and intra‐articular corticosteroids are allowed; administration or planned administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose of study vaccine(s) and ending 30 days after the last dose of study vaccine. This includes any type of vaccine such as (but not limited to) live, inactivated and subunit vaccines (e.g. inactivated and subunit influenza vaccines); administration of long‐acting immune‐modifying drugs (e.g. infliximab) within six months prior to the first vaccine dose or expected administration at any time during the study period; concurrently participating in another clinical study, at any time during the study period, in which the person has been or will be exposed to an investigational or a non‐investigational vaccine/product (pharmaceutical product or device); previous vaccination against VZV or herpes zoster and/or planned administration during the study of an herpes zoster or VZV vaccine (including an investigational or non‐registered vaccine) other than the study vaccine; History of herpes zoster; vaccination against diphtheria, or tetanus in the last 5 years or planned vaccination against diphtheria or tetanus during the study period, other than the study vaccine(s); administration of a combined tetanus, diphtheria and pertussis (Tdap) vaccine at any time prior to study entry; any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders); history of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines including prior severe allergic reaction following tetanus‐toxoid, diphtheria‐toxoid or pertussis‐containing vaccine; hypersensitivity to latex. Note: The investigational herpes zoster/su vaccine does not contain latex; acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C /99.5°F by oral route. The preferred route for recording temperature in this study will be oral. People with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator; administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period; pregnant or lactating female; female planning to become pregnant or planning to discontinue contraceptive precautions before 2 months after the last dose of study vaccine; any condition which, in the opinion of the investigator, prevents the person from participating in the study. Any condition which, in the judgment of the investigator, would make intramuscular (IM) injection unsafe; encephalopathy (e.g. coma, decreased consciousness, prolonged seizures) not attributable to an identifiable cause within 7 days of administration of a previous pertussis antigen‐containing vaccine; progressive or unstable neurologic disorder; history of Arthus‐type hypersensitivity reaction following a prior dose of a tetanus‐toxoid containing vaccine within the last 10 years; history of Guillain‐Barré syndrome within 6 weeks of receipt of a prior vaccine containing tetanus toxoid."
Interventions	Treatment group RZV + TDaPV co‐administration group: 1 injection of TDaPV IM deltoid region of the dominant arm and 1 injection of RZV IM deltoid region of the non‐dominant arm during the first visit, and a second injection of the RZV 2 months later (N = 412) Control group RZV + TDaPV not co‐administration group: 1 injection of TDaPV IM deltoid region of the dominant arm at the first visit; 1 injection of IM RZV 2 months later on the non‐dominant arm; and a second injection of RZV on the non‐dominant arm 2 months after the latter (N = 418)
Outcomes	Number of people with any serious adverse events for 14 months Number of people with any and related pIMDs for 14 months Number of people with any, grade 3, and related solicited general symptoms (myalgia, fatigue, headache, fever, shivering, and gastrointestinal) during the 7 days postvaccination Number of people with any and grade 3 solicited local symptoms (pain, redness and swelling) during the 7 days postvaccination Number of people with any, grade 3, and related unsolicited adverse events during the 30 days postvaccination Dropouts
Purpose of the study	"The purpose of this study is to assess immunogenicity, reactogenicity and safety of GSK Biologicals' HZ/su vaccine when its first dose is co‐administered with the Boostrix® vaccine in adults aged 50 years or older compared to administration of vaccines separately."
Funding sources	GlaxoSmithKline
Conflicts of interest	Not described
Notes	ITT analyses Grade 3 pain was pain that prevented normal activity. Grade 3 redness/swelling was redness/swelling spreading beyond (>) 100 mm. Assessed solicited general symptoms were fatigue, gastrointestinal (symptoms included nausea, vomiting, diarrhoea, and/or abdominal pain), headache, myalgia, shivering, and fever (defined as oral, axillary, rectal, or tympanic temperature equal to or above 37.5 °C). Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = temperature above 39.0 °C. Related = general symptom assessed by the investigator as causally related to vaccination. The reason for withdrawal for 1 participant was incorrectly entered into the electronic case report form as “lost due to Crohn’s disease”. The person withdrew from the study due to a combination of irritable bowel syndrome and time constraints associated with employment.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐label RCT
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label RCT
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label RCT
Incomplete outcome data (attrition bias) All outcomes	High risk	Participant flow not clear: "Not all subjects who were enrolled started the study due to elimination from statistical analyses or no vaccination received."
Selective reporting (reporting bias)	Low risk	All data that the authors proposed in their methodology were described in the results.
Other bias	Unclear risk	Insufficient information