Insert the Sponsor’s confidentiality statement, if applicable, otherwise delete.

The protocol should have a descriptive title that identifies the scientific aspects of the trial sufficiently to ensure it is immediately evident what the trial is investigating and on whom, and to allow retrieval from literature or internet searches.

Acronym or abbreviation used publicly to identify the clinical trial, if any. Delete this line from the table if not applicable.

A unique alphanumeric identifier for the trial, designated by the Sponsor, is a standard part of trial data, and should be included for most trials.

Enter 'Yes' or 'No'.

An optional field for use by the Sponsor at their discretion.

An optional field for use by the Sponsor at their discretion.

Enter the amendment identifier (e.g., amendment number). If this is the original instance of the protocol, leave blank.

Leave blank for original protocol. If an amendment applies to all sites in the trial, enter “global” and delete the Country, Region and Site Identifier fields. If amending a single-country study, enter “global”. If the amendment does not apply to all sites in the trial, select “Not Global” and utilize one of the identifiers based on amendment scope. Use the ISO-3166 region or country identifier (for example, DE or EU).

Enter the Sponsor’s unique identifier for investigational compound(s) in the trial. Add fields as needed.

Delete this line from the table if a nonproprietary name has not yet been assigned. Omit proprietary name fields if not yet established.

For trials combining investigational drugs or vaccines with devices, classify according to the phase of drug development.

Short title should convey in plain language what the trial is about and is suitable for use as “Brief Title” or “Title in Plain Language” in global clinical trial registries. It can also be suitable for use with informed consents and ethics committee submissions.

<Enter Sponsor Name> <Enter Sponsor Legal Address> <Enter Co-Sponsor Name> <Enter Co-Sponsor Legal Address> Provide the legal name of the individual or pharmaceutical or medical device company, governmental agency, academic institution, private organisation, or other organisation who takes primary responsibility for and initiates a clinical investigation. If more than one Sponsor, list the Primary Sponsor in this field. Local Sponsor Name and Address: <Enter Local Sponsor Name> <Enter Local Sponsor Address> In some countries, the clinical trial Sponsor may be the local affiliate company (or designee). In such cases, indicate in the Sponsor Local Name and Address Field.

Manufacturer name and address information is required only for protocols that include investigational device(s) and should not be included for other protocols. Include the manufacturer address only if the manufacturer is different than the Sponsor listed above. Add additional fields as needed if multiple investigational devices will be used in the trial. Delete this line from the table if not applicable.

<EU CT Number><IDE Number><FDA IND Number><JRCT Number><NCT Number><NMPA IND Number><WHO/UTN Number><Other Regulatory Agency Identifier Number> Include all numbers that are applicable for the trial and available at the time of protocol or amendment finalisation. Delete prompts for numbers not available at the time of document finalisation. Delete unused fields. Add fields for “other” if more than one is needed.

<Enter Approval Date or state location where information can be found> All versions should be uniquely identifiable. Use the CDISC date format (dd/mmm/yyyy, for example 07/JUN/2015) to indicate the date the protocol (or amendment) was approved by the Sponsor.

Include either the sponsor signature (name and title of sponsor signatory and signature date) or the statement {This protocol was approved via <describe method> as described on the approval page appended to the document.}.

Enter contact information for Medical Expert (as designated by sponsor) or state location where information can be found.

Report Serious Adverse Events to the sponsor <Enter SAE reporting method(s)> Refer to Section 9.4 for detailed reporting instructions.

State {Not applicable. This protocol has not been amended.} or state {This protocol has been amended previously. Details of prior amendments are presented in Prior Protocol Amendment(s).} or include Current Amendment details as appropriate (See instructions).

Summarize the primary and secondary objectives and any associated estimands. Consider including a copy of the from Section 3 of the protocol and follow all the same instructions.

see Template instructions

Enter the numeric value for the number of arms in the trial. For trials with a different number of arms in different periods, populate this field based on the total number of arms.

For designs in which these details may differ in one or more trial periods, answer according to the portion of the trial in which the highest number of blinded roles occurs. More details can be provided in Section 6.6 of the protocol. State: Blinded roles: The following roles indicated will not be made aware of the treatment group assignment during the trial: [blinded roles]. Not applicable (No blinding) indicates an open-label trial.

State the expected number of participants to be assigned to trial intervention/enrolled. Indicate whether the number provided is the target or maximum number of individuals to be randomly assigned to trial intervention/enrolled. A [Target/ Maximum] of [[Enter Number of Participants]] participants will be [randomly assigned to trial intervention/ enrolled].

See Template instructions.

Indicate whether any committee(s) will be reviewing data while the trial is ongoing, and the type of committee. Common examples include Data Monitoring Committee, Dose Escalation Committee, or Endpoint Adjudication Committee; describe others, if applicable. List independent committees in the space indicated. Other committees may be included at the Sponsor’s discretion in the separate space provided. Committees listed here should be fully described in Section 11.3. Indicate N/A if no independent committees will be involved in the trial. Delete Other Committees if not applicable.

The purpose of this section is to provide a visual depiction of the trial design, orienting users of the protocol to the key features of the design. The schema depicts the trial arms, the flow of individual participants through the progression of trial period(s)/epochs (such as screening, washout/run-in, intervention, and key milestones [for example, randomisation, cross-over, end of treatment]). For complex trials, additional schemas may be added to describe activities or trial periods in greater detail.

The schedule of activities must capture the procedures that will be accomplished at each trial visit, and all contact with participants, for example, telephone contacts. This includes any tests that are used for eligibility, participant randomisation or stratification, or decisions on trial intervention discontinuation. Allowable windows should be stated for all visits and procedures. A tabular format is recommended.

Explain why the trial is needed, why the research questions being asked are important. Do not restate the IB.

The benefit summary should be written from the perspective of an individual participant, and should describe any physical, psychological, social, legal, or any other potential benefits to individual participants as a result of participating in the trial, addressing immediate potential benefits and/or long-range potential benefits. Clearly state if no benefits to an individual participant can be anticipated, or if potential benefits are unknown. For early clinical trials such as Phase 1, benefits for an individual participant (other than those of altruism) are expected to be minimal. Benefits to society in general may also be included but should be described separately.

Trial Intervention - Describe risks related to trial-specific treatments and interventions. For the protocol, focus only on the relevant key risks for THIS trial. Provide a brief description of strategies to mitigate identified risks or provide a cross-reference to the relevant protocol section.

Trial Procedures - Consider risks associated with the design (for example, placebo arm) and procedures specific to THIS trial (for example, biopsies), and any measures to control the risks. Provide a brief description of strategies to mitigate identified risks or provide a cross-reference to the relevant protocol section. This is not intended to be an exhaustive list of all possible risks associated with trial procedures but should focus on the unique risks inherent in the design or less common or high-risk procedures. As above, provide a brief description of strategies to mitigate identified risks or provide a cross-reference to the relevant protocol section.

Other - Consider risks associated with other items (for example, comparators, challenge agents, imaging agents, medical devices). Insert a line for each, as needed.

Provide a succinct, concluding statement on the perceived balance between risks that have been identified from cumulative safety data, protocol procedures, and anticipated efficacy/benefits within the context of the proposed trial. Risks need to be assessed against the benefits for the individual participant at least once a year.

List of key characteristics, such as demographic characteristics (e.g., age, sex) and clinical characteristics (e.g., prior therapies, symptoms, severity, biomarker status)

List of key aspects of treatment regimens in each study group, including at least investigational agents, dosage, and administration route

Definition of the endpoint

Description of the population-level summary (e.g., mean difference, relative risk)

This may later be replaced with a repeatable section. For each intercurrent event, provide (1) Description of Intercurrent Event 1 (e.g., permanent discontinuation of trial intervention) and (2) Description of the strategy to address the intercurrent event (e.g., a treatment policy strategy); cross-reference the justification in Section 4

[List of key characteristics, such as demographic characteristics (e.g., age, sex) and clinical characteristics (e.g., prior therapies, symptoms, severity, biomarker status)

List of key aspects of treatment regimens in each study group, including at least investigational agents, dosage, and administration route

Definition of the endpoint

Description of the population-level summary (e.g., mean difference, relative risk

This may later be replaced with a repeatable section. For each intercurrent event, provide (1) Description of Intercurrent Event 1 (e.g., permanent discontinuation of trial intervention) and (2) Description of the strategy to address the intercurrent event (e.g., a treatment policy strategy); cross-reference the justification in Section 4

[List of key characteristics, such as demographic characteristics (e.g., age, sex) and clinical characteristics (e.g., prior therapies, symptoms, severity, biomarker status)

List of key aspects of treatment regimens in each study group, including at least investigational agents, dosage, and administration route

Definition of the endpoint

Description of the population-level summary (e.g., mean difference, relative risk

This may later be replaced with a repeatable section. For each intercurrent event, provide (1) Description of Intercurrent Event 1 (e.g., permanent discontinuation of trial intervention) and (2) Description of the strategy to address the intercurrent event (e.g., a treatment policy strategy); cross-reference the justification in Section 4

see Template instructions

If applicable, describe any stakeholder (for example, patient, healthcare professional and patient advocacy groups) involvement in the design of the trial and any suggestions implemented.

Provide a rationale for the trial intervention model selected in Section 4.1, Description of Trial Design with a cross-reference to Section 6.2, Rationale for Investigational Intervention(s). Rationale for choice of comparator, if applicable, should be described separately in Section 4.2.5, Rationale for Comparator. A rationale for the choice of trial population should be described separately in Section 5.1, Description of Trial Population and Rationale.

Provide a rationale that the trial duration is appropriate for a reliable and relevant evaluation of the trial intervention per the trial objective(s).

Provide a rationale for the trial estimand(s) described in Section 3. This should include a rationale that the selected endpoint(s) are clinically relevant and provide a reliable and valid measurement of the intended intervention effect. It should also include a rationale for the selected strategies for handling intercurrent events.

If applicable, provide a rationale for any interim analysis planned with respect to its purpose (for example, stopping the trial early for efficacy or futility) and timing.

If applicable, provide a rationale for the type and choice of control selected for the trial (for example, placebo, active drug, combination, historical). Describe any known or potential problems associated with the control group selected in light of the specific disease and intervention(s) being studied. If comparators will differ by region, describe. The rationale for dose/dose regimen is explained in Section 6.2.

If applicable, provide a rationale for the use of an adaptive or novel design.

Discuss rationale for any additional aspects of the design not addressed above.

If applicable, describe any trial-specific stopping rules, including guidance on when the trial should be stopped for safety reasons, when a cohort or dose escalation should be terminated, and/or when a given treatment arm should be terminated. If applicable, describe any rules that may result in a temporary pause of dosing and/or enrollment into the trial and criteria for restarting enrollment. Ensure that the trials stopping rules are aligned with the specifications that are described in Section 10.9 for Interim Analyses.

Define key timepoints in the trial, including trial start and end dates. For example, a key timepoint definition for start of trial might be when the informed consent is signed by the first participant and a key timepoint definition for end of trial might be when participants are no longer being examined or the last participant’s last study assessment has occurred. If applicable, consider local regulatory requirements for these and other definitions (for example, the first act of recruitment). If appropriate, provide a cross-reference to Section 11.6

If applicable, describe any possibilities for access to trial intervention, if any, beyond completion of the trial. Planned extension trials, if described above in Section 4.1 do not need to be repeated.

Describe the population selected (for example, healthy participants, adult participants, paediatric participants) and how the enrollment criteria reflect the populations that are likely to use the drug if approved. Specify the population age range (for example, ≤3 months, ≥18 to ≤80 years old) including the time point at which qualification for age criteria is determined (for example, at time of screening vs randomization for paediatric trials). Specify any key diagnostic criteria for the population (for example, “acute lung injury”, or a specific biomarker profile). If applicable, describe similar conditions or diseases and their differential diagnosis. If the target population is based on a subset of the entire trial population defined by a particular characteristic measured at baseline (e.g., a specific biomarker), this subset should be defined and justified in this section. Provide a rationale for the trial population ensuring that the population selected is well defined and clinically recognisable. Describe how the selected population can meet the trial objectives and how the enrollment criteria reflects the targeted populations. Justify whether the trial intervention is to be evaluated in paediatric participants, in adults unable to consent for themselves, other vulnerable participant populations, or those that may respond to the trial intervention differently (for example, elderly, hepatic or renally impaired, or immunocompromised participants).

Inclusion criteria are characteristics that define the trial population, for example, those criteria that every potential participant must satisfy, to qualify for trial entry.

Exclusion criteria are characteristics that make an individual ineligible for participation.

Specify the definitions of Participant of childbearing potential and Participant of non-childbearing potential, or state Not Applicable.

Specify the contraceptive methods required and duration of use, or state Not Applicable.

In the following subsections, describe any restrictions during the trial pertaining to lifestyle and/or diet, intake of caffeine, alcohol, or tobacco, or physical and other activities. If not applicable, include a statement that no restrictions are required.

If applicable, describe any restrictions on diet (for example, food and drink restrictions, timing of meals relative to dosing).

If applicable, describe any restrictions on the intake of caffeine, alcohol, tobacco, or other restrictions.

If applicable, describe any restrictions on activity (for example, in first-in-human trials, activity may be restricted by ensuring participants remain in bed for 4 to 6 hours after dosing).

If applicable, describe restrictions on any other activity (for example, blood or tissue donation); or any other activity restrictions, such as on driving, heavy machinery use, or sun exposure.

Indicate how screen failure will be handled in the trial, including conditions and criteria upon which rescreening is acceptable. If applicable, indicate the circumstances and time window under which a repeat procedure is allowed for screen failure relating to specific inclusion/exclusion criteria for the trial.

Enter a Table of Trial Interventions. See Template Instructions for details.

The investigational trial intervention is the product used in the trial as part of trial objectives. Other trial interventions that are not part of trial objectives (not an investigational role in this trial) are described in Section 6.10 Description of Non-investigational trial interventions. For IMP, NIMP, AxMP designations based on local legislation, please refer to Table of Trial Interventions above. Describe the investigational trial intervention to be administered in each arm of the trial and for each period of the trial including route and mode of administration, dose, dosage regimen, duration of intervention, use, packaging and labelling. Refer to approved regional labelling, as appropriate. For drug/device combination products, include details on the configuration and use of the device and device manufacturer. A device user manual may be referenced in this section.