📚 Part of the OBX-319 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.

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Informed Consent Form (OBX319-301)

Document ID: TMF-001
Version: 1.0
Change History: 1.0 — Initial issue.
Standard(s): ICH E6(R3)

Informed Consent Form — OBX319-301

You are invited to take part in a research study of an investigational medicine, OBX-319, for Systemic Lupus Erythematosus (moderate-to-severe active). Please read this form carefully and take as much time as you need. A member of the study team will explain the study to you, answer your questions, and ask you to sign only if you decide to take part. You may take a copy of this form home to discuss with your family or your own doctor before deciding.

OBX-319 is a laboratory-manufactured antibody medicine (a "monoclonal antibody"). It is a bispecific antibody, which means each molecule is built to recognise two different targets at the same time — two markers called CD19 and CD20 that sit on the surface of a type of white blood cell known as a B cell. In lupus, B cells are believed to drive the immune system to attack your own body. By attaching to both CD19 and CD20, OBX-319 is designed to lower the number of these B cells in your blood, with the aim of reducing lupus disease activity. Because both markers are targeted together, the reduction in B cells is expected to be more complete than with medicines that target only one marker. OBX-319 is given as an injection under the skin (subcutaneous injection).

This medicine is investigational. That means it has been tested in a limited number of people and is not approved by regulatory authorities for the treatment of lupus. The purpose of this study is to find out how well OBX-319 works and how safe it is when added to your usual lupus treatment, and to compare two different doses of OBX-319 against a placebo (an injection that looks the same but contains no active medicine).

About 480 adults with moderate-to-severe active lupus are expected to take part at study centres in several countries. Your participation, if you agree, would last about 52 weeks of treatment, followed by a period of safety follow-up after your last dose (described below). Taking part is entirely voluntary. You may decide not to join, and if you do join you may withdraw at any time, for any reason, without penalty and without any effect on the medical care you would otherwise receive. If you choose not to take part, or to stop, your usual lupus treatment will continue to be available to you.

Study procedures

Screening. Before you can join, the study team will confirm that you are eligible. This screening period includes a review of your medical history and current lupus medicines, a physical examination, measurement of your lupus disease activity using a standard scoring tool (SLEDAI-2K), and blood and urine tests. Because OBX-319 lowers the activity of part of your immune system, screening will also include tests for certain infections that could become active during treatment — including hepatitis B, hepatitis C, and tuberculosis. If any of these are found, you may not be able to take part, or you may need additional evaluation or treatment first.

Groups and blinding. If you are eligible and agree to take part, a computer will place you by chance (like flipping a coin) into one of three groups in equal proportion (1:1:1):

• a higher dose of OBX-319,
• a lower dose of OBX-319, or
• placebo (no active medicine).

This is a randomized, double-blind study. "Double-blind" means that neither you nor your study doctor will know which group you are in during the study. This is done so that the results are not influenced by expectations. In an emergency, your study doctor can find out which treatment you received if that information is needed for your medical care.

Your usual lupus treatment. OBX-319 or placebo is given in addition to your standard-of-care lupus medicines (for example, antimalarials, corticosteroids, or other immune-modifying medicines). You will continue your background treatment during the study, and the study team will give you instructions about any dose adjustments.

Study treatment. OBX-319 or placebo is given as an injection under the skin on a schedule set by the study protocol. A trained member of the study team will usually give the injections at the study centre. You will be observed after dosing, particularly after the first injections, so the team can watch for any reaction.

Study visits and assessments. Over the roughly 52-week treatment period you will come to the study centre for scheduled visits. At these visits the study team may:

• perform physical examinations and check your vital signs;
• score your lupus disease activity (including SLEDAI-2K) and review your symptoms;
• take blood and urine samples for routine safety tests (such as blood counts, kidney and liver tests);
• take blood samples to measure the amount of OBX-319 in your body (pharmacokinetics);
• take blood samples to measure how your immune system responds — including the number of your CD19-positive B cells, and lupus-related laboratory markers such as anti-double-stranded-DNA antibodies (anti-dsDNA) and complement proteins (C3 and C4);
• take blood samples to check whether your body has made antibodies against the medicine itself (anti-drug antibodies, described under Risks below).

The amount of blood taken at each visit is small and will be explained to you. You will be asked to keep your scheduled appointments so that these safety and laboratory measurements can be done on time.

How OBX-319 behaves in the body. In earlier and ongoing studies, OBX-319 produced a marked, near-complete fall in the number of circulating B cells (for example, from roughly 210 to about 7 cells per microlitre of blood), whereas placebo did not change these counts. Your B cells are expected to return over time after treatment stops, but the speed of recovery can differ from person to person. Because of this, safety follow-up continues after your last dose until your B cells recover to an acceptable level, and the study team will keep monitoring you during that time.

Pregnancy, contraception, and vaccines. The effects of OBX-319 on an unborn baby are not known, and medicines of this kind can cross into a developing baby and lower its B cells. If you can become pregnant, you must have a negative pregnancy test before starting and must use an effective method of contraception during the study and for a period after your last dose, as the study team will explain. Tell the study team immediately if you think you may be pregnant. You should not receive "live" vaccines during the study or for a defined period afterwards, because your reduced immune activity may make live vaccines unsafe or less effective; discuss any planned vaccinations (including routine or travel vaccines) with the study team first.

Risks and benefits

Because OBX-319 is investigational, not all of its risks are known, and new risks may be identified during the study. The study team will explain the foreseeable risks below and will tell you promptly about any new information that could affect your willingness to continue.

Risks related to lowering B cells (the main expected risks). OBX-319 works by reducing B cells, which are part of your immune defence. Lowering them can increase your risk of:

• Infections, including serious and opportunistic infections. You may get infections more easily, and some could be severe or unusual (infections that mostly affect people with a weakened immune system). Existing infections, such as hepatitis B or tuberculosis, could become active again — this is why you are screened for them before joining. Tell the study team right away about any fever, cough, unusual tiredness, or other signs of infection.
• Low antibody levels in the blood (hypogammaglobulinaemia). Over time, reducing B cells can lower the level of protective antibodies (immunoglobulins) your body makes. This can add to the risk of infection, particularly with continued treatment. Your antibody levels will be monitored, and in some cases treatment may be paused or additional measures taken.

Injection and infusion-type reactions. You may have reactions at or around the injection site, such as redness, swelling, pain, or itching. Less commonly, an injection can trigger a reaction that affects the whole body (for example fever, chills, rash, changes in blood pressure, or, rarely, a serious allergic reaction). You will be observed after dosing so that any reaction can be treated. Tell the team immediately if you feel unwell during or after an injection.

Immune response to the medicine (immunogenicity). Your body may recognise OBX-319 as foreign and make antibodies against it (anti-drug antibodies). In some people these antibodies can reduce how well the medicine works, or contribute to injection-related or allergic reactions. This is why blood samples are taken during the study to check for these antibodies.

Blood draws. Taking blood may cause pain, bruising, light-headedness, or, rarely, infection at the needle site.

Reproductive and unknown risks. As noted above, the effects on pregnancy, an unborn baby, and fertility are not known, which is why contraception is required. There may also be risks that are not yet known.

Possible benefits. You may or may not benefit personally from taking part. If you are in one of the OBX-319 groups, your lupus disease activity may improve; however, this cannot be guaranteed, and if you are in the placebo group you will not receive active study medicine. Whether or not you benefit, the information gained from this study may help doctors and people with lupus in the future.

Alternatives to taking part. You do not have to join this study to receive treatment for your lupus. Standard-of-care therapies and, in some cases, other approved medicines or clinical trials may be available to you. The study team will discuss these alternatives with you so you can make an informed choice.

Confidentiality

Your coded data may be reviewed by the sponsor (Virtual Biopharma Inc.) and organisations working on its behalf, by the ethics committee/IRB that oversees this study, and by regulatory authorities. Information collected about you during the study is labelled with a study code and your initials rather than your full name, to help protect your privacy. Records that directly identify you (such as your name and contact details) are kept by the study team at the site and are not sent to the sponsor.

The people and organisations who may look at your study records — to check that the study is being run correctly and that the data are accurate — include the study doctor and site staff, the sponsor and its authorised representatives (such as monitors and auditors), the ethics committee/IRB, and regulatory authorities in this and other countries (for example, health authorities reviewing the medicine). By signing this form you allow these parties to access your relevant records for these purposes.

Some of your blood samples may be stored and analysed to measure the medicine, your B cells, lupus-related markers, and anti-drug antibodies, and to support the safety and quality evaluation of the medicine. Samples are handled under the same coded, confidential conditions. If study results are published or presented, you will not be identified by name, and no information that could directly identify you will be included. ICH E6(R3)/GCP.

If you have questions about the study, your rights as a participant, or a possible study-related injury, or if you wish to withdraw, contact the study doctor or study team using the details provided to you separately with this form.