A clinical trial to compare obinutuzumab with mycophenolate mofetil (MMF) in children and young adults with a kidney disorder called idiopathic nephrotic syndrome

1. Why is the INShore clinical trial needed?

Childhood-onset idiopathic nephrotic syndrome is a kidney disorder that starts in childhood and causes the body to pass too much protein in the urine. The condition causes swelling (also known as edema) especially in the face, legs, and feet, and changes in the person’s urine. In most cases the cause is not known; this is called ‘idiopathic’.

Current standard of care for childhood-onset idiopathic nephrotic syndrome is a combination of steroids and immunosuppressive drugs (such as a drug called mycophenolate mofetil [MMF]). However, in many people who receive these treatments, the protein in the urine keeps coming back. This is called ‘relapsing’. Treatment with steroids is also linked to the risk of certain side effects. Researchers are looking for new treatments which are more effective and have better long-term health outcomes.

2. How does the INShore clinical trial work?

This clinical trial is recruiting children and young people between 2 and 25 years of age with idiopathic nephrotic syndrome that has started during childhood.

The purpose of this clinical trial is to compare the effects, good or bad, of obinutuzumab versus MMF in people with childhood-onset idiopathic nephrotic syndrome. People who take part in this clinical trial will receive either obinutuzumab or MMF.

During a ‘52 Week Treatment Period’ participants will be given the clinical trial treatment (obinutuzumab or MMF) for 52 weeks (around 1 year), and will be seen regularly (at visits between 2 and 8 weeks apart) by the clinical trial doctor, for up to 12 visits. These clinic or home-nursing visits will include checks to see how the participant is responding to the treatment and any side effects they may be having.

After the ‘52 Week Treatment Period’ participants may enter the ‘Post Week-52 Extension Period’. They will be seen by the clinical trial doctor every 12 weeks until the last participant who joins the clinical trial reaches their Week 52 visit.

Participants will enter the ‘Safety Follow-up Period’ at either 1) time of early withdrawal, 2) at the time the last participant reaches their Week 52 visit, or 3) if the sponsor terminates the trial, and will continue to be seen by the clinical trial doctor approximately every 3 months. Participants who have not received obinutuzumab will return for a visit only once during the ‘Safety Follow-up Period’, 3 months after they have withdrawn or completed the trial. Participants who have received obinutuzumab will be monitored throughout the safety follow-up period until they have fulfilled both of the following criteria:

1. Specific immune cells, known as peripheral B cells, have returned to pre-treatment levels (i.e. the same levels as before being given obinutuzumab treatment) or to within the normal range for this population, whichever is lower
2. The last dose of obinutuzumab was at least 12 months ago

OR, until the last participant enrolled completes the safety follow-up requirements, up to a maximum of 18 months from the last dose of obinutuzumab, after which time the clinical trial will end.

Participants are free to stop trial treatment and leave the clinical trial at any time.

3. What are the main endpoints of the INShore clinical trial?

The main clinical trial endpoint (the main results that are measured in the trial to see if the treatment has worked) is: the effectiveness of obinutuzumab compared with MMF, as measured by the number of participants who are in ‘complete remission’ at 1 year. Complete remission is defined as undetectable protein in the urine, with no relapses during the treatment period that require the use of systemic corticosteroids or rescue medications.

The other clinical trial endpoints include the time to the first relapse, changes in how tired (fatigued) the participant is feeling, how well participants feel on a daily basis (general quality of life), evaluation of swelling in different parts of the body, and the number and seriousness of any side effects that occur whilst on treatment.

4. Who can take part in the INShore clinical trial?

People can take part in this trial if they are aged between 2 and 25 years, have been diagnosed with idiopathic nephrotic syndrome before18 years of age, have had at least one ‘relapse’ in the 6 months before the start of the trial, and are in ‘remission’ in the week before they start the trial (three daily tests in a row that show no protein in the urine, and no swelling in the face or body).

People may not be able to take part in this trial if they have a history of steroid resistant nephrotic syndrome, a history of genetic defects known to directly cause nephrotic syndrome, have had treatment with certain other immunosuppressive medications to prevent relapse within a specific time frame before potentially starting the trial, are pregnant or breastfeeding, or are planning to become pregnant.

5. What treatment will participants be given in this clinical trial? 

Everyone who joins this clinical trial will be split into two groups randomly (like flipping a coin) and given either:

●          Group A: Obinutuzumab, given as an infusion into the vein on Days 1, 15, 168 (Week 24) and Day 182 (Week 26) during the ‘52 Week Treatment Period’

●          OR, Group B: MMF, given as either a tablet or liquid by mouth every day of the ‘52 Week Treatment Period’

After the ‘52 Week Treatment Period’ participants may continue into the ‘Post Week-52 Extension Period’:

●          Participants in Group B will stop MMF treatment at Week 52 or it will be stopped gradually over 12 weeks (by Week 64)

●          If a participant in either Group A or B relapses before or during the ‘Post Week-52 Extension Period’ they may be treated with obinutuzumab, MMF, or another medication that their clinical trial doctor recommends

Participants will have an equal (1 in 2) chance of being placed in either group. This is an open-label trial, which means everyone involved, including the participants, parents, caregivers and trial doctors will know which group the participant is in. 

6. Are there any risks or benefits in taking part in this clinical trial?

The safety or effectiveness of the experimental treatment or use is not fully known at the time of the trial. Most trials involve some risks to the participant, although it may not be greater than the risks related to routine medical care or the natural progression of the health condition. Potential participants will be told about any potential risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. These will all be described in an informed consent document (a document that provides people with the information they need to make a decision to volunteer for a clinical trial). A potential participant should also discuss these with members of the research team and with their usual healthcare provider. Anyone interested in taking part in a clinical trial should know as much as possible about the trial and feel comfortable asking the research team any questions about the trial.

Risks associated with the clinical trial drugs

Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drugs used in this clinical trial. Side effects can be mild to severe and even life-threatening and can vary from person to person.

Obinutuzumab

Potential participants will be told about the known side effects of obinutuzumab and where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs. Obinutuzumab will be given by intravenous infusion (this means it is given directly into a vein). Participants will be told about any known side effects of intravenous infusion.

MMF

Potential participants will be told about the known side effects of MMF, and where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs. MMF will be given by mouth (known as oral administration) either as a tablet or as a liquid. Participants will be told about any known side effects of oral administration.

Potential benefits associated with the clinical trial

Participants' health may or may not improve from participation in the clinical trial, but the information that is collected may help other people who have a similar medical condition in the future.

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For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow this link to ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT05627557