ALXN1210-NEPH-202 - Ravulizumab in LN or IgAN
Research type
Research Study
Full title
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)
IRAS ID
294776
Contact name
Elizabeth Lightstone
Contact email
Sponsor organisation
Alexion Pharmaceuticals, Inc.
Eudract number
2020-001537-13
ISRCTN Number
ISRCTN00000000
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
148192, IND
Duration of Study in the UK
2 years, 2 months, 21 days
Research summary
This study involves an investigational treatment called ALXN1210, also known as ravulizumab, which is being developed for the treatment of Immunoglobulin A Nephropathy (IgAN) and Proliferative Lupus Nephritis (LN).
IgAN and LN are conditions that cause chronic kidney disease. Overtime, some patients develop end-stage renal disease (ESRD) requiring dialysis or kidney transplant.
The study treatment binds to the C5 protein of the complement system. The complement system is part of the body’s immune system (system that fights against infections). Dysregulation of the complement system is a contributing factor for the cause of IgAN and LN. The study treatment works by reducing complement activity. The purpose of the study is to evaluate the safety and efficacy of the study treatment in participants with IgAN and LN. It is expected that approximately 120 participants aged at least 18 years will take part in this study at approximately 105 Sites Globally.
ALXN1210 has been approved for the treatment of patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) and patients with atypical hemolytic uremic syndrome (aHUS) under the brand Ultomiris®.Participants in this study will be required to:
• Attend all study visits and complete all tests throughout the study.
• Be honest and truthful about their medical history and current conditions and medicines they are taking.
• Tell the study doctor of any new medications they may take during their participation in this study.
• Tell the study doctor of any problems they may be having during the study, including any injuries or illnesses.
• Female patients of childbearing potential must use acceptable methods of contraception as discussed with the study doctor, starting at Screening and continuing for at least 8 months after the last dose of study treatment.
• Tell the study doctor if the participant or the participant’s partner becomes pregnant.
• Participants cannot take part in any other studies involving treatment with a drug or medical device as they may interfere with the results of this study
• Participant are required to carry the Patient Safety Card at all times.
The duration of participation in the study is anticipated up to 86 weeks (approximately 1.6 years)Results Summary
In this study, a drug called ravulizumab was tested. The researchers wanted to know how effective, safe and tolerable ravulizumab was in the treatment of adults with either proliferative lupus nephritis (also known as LN) or immunoglobulin A nephropathy (also known as IgAN). To test this, researchers measured how much protein was in urine (proteinuria) after 26 weeks of treatment, as compared to proteinuria at the start of the study (also called the study “baseline”). Clinical studies aim to answer questions about specific diseases, or treatment procedures, and involve participants with medical conditions or healthy volunteers. Clinical studies to develop new treatments happen in four stages, from Phase 1 to Phase 4, each investigating specific questions about the treatment. This was a Phase 2 study. In general, Phase 2 studies look at the overall risks and benefits of a new treatment. The goal is to determine how safe a drug is, how it is broken down and eliminated by the body, and whether it works as expected in treating the disease and participants being evaluated. These trials usually involve a relatively small number of participants.What are LN and IgAN?
LN is a rare, complex and systemic autoimmune disease that can occur in people who have systemic lupus erythematosus. An autoimmune disease is a condition in which the immune system mistakenly attacks one’s own body. In LN, the immune system attacks the kidneys. When this occurs, tissue damage in the kidneys happens via activation of a specific part of the immune system called the alternative complement system. This tissue damage can decrease kidney function. The complement system normally plays an important role in fighting infections and clearing damaged cells from our body. However, in LN, the complement system is inappropriately activated and injures the kidneys. IgAN is a rare disease caused by the overproduction of an abnormal type of immunoglobin A (known as IgA). IgA is a type of antibody of the immune system that is abundant in mucus secretions, such as saliva and tears. These abnormal antibodies accumulate in the kidney, leading to tissue damage via activation of the alternative complement system. Like with LN, instead of the complement system helping fight infections and clearing damaged cells, the complement system with IgAN is inappropriately activated and injures the kidneys. In both LN and IgAN the damage to the kidneys from the complement system can lead to diminished kidney function.
What are the symptoms of LN and IgAN?
Adults with LN or IgAN experience progressively worsening kidney damage. Symptoms vary, but often include changes in urination frequency, fatigue, confusion, nausea, loss of appetite and overall discomfort. Eventually, kidney disease caused by both LN and IgAN can lead to the need for dialysis or transplant. Both diseases can be fatal from continuous and cumulative kidney damage.
What treatments are available for LN or IgAN?
Most people who have LN in stages similar to those in this study receive a combination of corticosteroids, hydroxychloroquine and other medications that calm the immune system. Most people who have IgAN in similar stages receive medication more commonly prescribed for high blood pressure, in addition to medications that calm the immune system. Other IgAN medications may include diabetes drugs and diuretics (medicines that help control fluid retention).
What were the treatments researched in this study?
In this study, participants received either ravulizumab or placebo, in addition to regular medication, which was given throughout the study. A placebo looks like the treatment but has no active treatment ingredient in it. Ravulizumab and placebo were given as intravenous infusion (through a vein into the bloodstream). During the Initial Evaluation Period, participants were given either ravulizumab or placebo, both at amounts tailored to the participant’s body weight. Participants received ravulizumab or placebo on the first day, then again two weeks later. After the second dose, participants received ravulizumab or placebo once every other month. Participants were given “double-blind” ravulizumab or placebo, which means that neither the participants nor the study doctors knew which dose/treatment was received. Participants were randomised (assigned by chance) to receive either ravulizumab or placebo during the Initial Evaluation Period. The researchers performed a 2:1 “randomisation” which means that twice as many participants were placed into ravulizumab treatment group than into the placebo group. During the Extension Period, participants with LN remained on either ravulizumab or placebo every other month. Participants with IgAN all received ravulizumab every other month; no participants with IgAN received placebo. In case of worsening LN symptoms, participants could be given additional regular medication. During the follow-up period, all participants stopped taking ravulizumab or placebo and used only their regular medication. They remained in the study for safety and any long-term changes.
Who could take part in this study?
To be able to take part in the study, participants had to meet the following requirements:
- Male or female adults aged 18-75
- Confirmed diagnosis of LN or IgAN
- ProteinuriaIndividuals were unable to take part if they had uncontrolled high blood pressure or other medical conditions that could interfere with understanding of the study results. Also, those with severe kidney damage or kidney failure could not participate in the study. Neither could adults with major infections, or those who had previously received an organ or bone marrow transplant. Participants consented to be in the study.
How many participants took part in this study?
42 women + 15 men = 57 participants with LN
30 women + 36 men = 66 participants with IgANParticipants with LN were between 18 and 72 years of age at the start of the study, whereas participants with IgAN were between 21 and 69 years of age at the start of the study. Participants were randomly put into groups. Two-thirds received the study drug and one-third received a placebo. The study started in January 2021 and ended in August 2025.
WHERE WAS THIS STUDY DONE?
The study took place in 85 study centres in 14 countries across South Korea, United States, United Kingdom, Canada, Australia, Spain, France, Taiwan, Italy, Poland, Netherlands, Singapore, Sweden and Germany.
WHAT WERE THE RESULTS OF THIS STUDY?
The researchers wanted to see how safe, effective and tolerable ravulizumab was in the treatment of participants with LN or IgAN after 26 weeks.In participants with IgAN, decrease in proteinuria was greater with ravulizumab (down 41.9%) than with placebo (down16.8%). In participants with LN, there was no difference between ravulizumab and placebo.
What were the safety findings in this study?
A side effect is any symptom a participant has during the study which may or may not be related to the study treatment. Related side effects are unwanted medical events that happen during the study, and are considered to be related to the study treatment. Side effects are classified as either “mild”, “moderate” or “severe” in intensity. A serious side effect is thought to be an important medical event (e.g. requires a person to be admitted to the hospital, is life-threatening, causes disability or causes death). Side effects can vary from person to person. Researchers keep a record of all the side effects participants have when new treatments are studied. This helps researchers to determine which side effects occur as a result of the study treatment, and which occur by chance or because of the participant’s underlying disease.What serious side effects did participants have in this study?
Overall, 14 out of 57 participants (24.6%) with LN had serious side effects during the study. Of those, 11 out of 38 participants (28.9%) were in the ravulizumab group and 3 out of 19 participants (15.8%) were in the placebo group. In these 14 participants, most serious side effects were thought by study doctors to be unrelated to the study drug. A total of 2 out of 38 participants (5.3%) with LN who were receiving ravulizumab experienced a serious side effect: upper respiratory tract infection and neutropenia (low neutrophils, a type of white blood cell that helps fight infections). These two side effects were thought by study doctors to be related to treatment with ravulizumab. Overall, 1 out of 43 participants (2.3%) with IgAN had a serious side effect of COVID-19, which was thought by study doctors to be unrelated to the study drug.
What side effects did participants have in this study?
Overall, 51 out of 57 participants (89.5%) with LN had side effects during the study. Of those, 34 out of 38 participants (89.5%) were in the ravulizumab groups, and 16 out of 19 participants (84.2%) were in the placebo group. The majority of side effects were thought by study doctors to be mild in intensity and not related to the treatment. A total of 11 out of 38 participants (28.9%) with LN had a side effect that was thought by study doctors to be related to ravulizumab. Upper respiratory tract infection and cough were the only related side effects to occur in more than one participant. Both occurred in 2 out of 38 participants (5.3%). Overall, 51 out of 66 participants (72.3%) with IgAN had side effects during the study. Of those, 38 out of 43 participants (88.4%) received ravulizumab throughout the study, and 19 out of 23 participants (82.6%) received placebo during the Initial Evaluation Period and then switched to ravulizumab during the Extension Period. The majority of side effects were thought by study doctors to be mild in intensity and not related to the treatment. A total of 10 out of 43 participants (23.3%) with IgAN had a side effect that was thought by study doctors to be related to ravulizumab. Nasopharyngitis (a common cold) and COVID-19 were the only two side effects to occur in 10% or more of participants with IgAN while receiving ravulizumab. Nasopharyngitis occurred in 9 (20.9%) participants; COVID-19 occurred in 7 (16.3%) participants.Were there any other important safety findings in this study?
4 out of 38 participants (10.5%) with LN stopped taking ravulizumab because of side effects. Of these, one (urticaria, commonly called hives) was considered related to ravulizumab. No participants with IgAN stopped taking ravulizumab because of a side effect.
How has this study helped participants and researchers?
The information collected in this study showed that ravulizumab decreased proteinuria in adults with IgAN but not in adults with LN. The majority of side effects were thought by study doctors to be unrelated to ravulizumab. Before a treatment can be approved for patients to use, researchers look at the results of many studies to decide which treatments work best and are safe. If you have any questions about ravulizumab for the treatment of LN or IgAN, please talk to your doctor. You should not change your treatment based on the results of this study without talking to a doctor first.
Useful clinical study websites
This document provides a summary of the main results of the study. It includes information about the side effects that happened to participants in the study and the results of the questions the researchers wanted to answer. This summary was reviewed for readability by a patient advocacy group.Complete study results are available to read at the following clinical study register(s):
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Cnottingham2.rec%40hra.nhs.uk%7C98672af6bb0b42130f3608de7858af65%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639080519460222853%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=1%2FWgzEUJ989dke%2BfW1uEnihm4KZ%2BfFiodFofMjIx3eE%3D&reserved=0Use the study number NCT04564339 to search for more information on this website.
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Cnottingham2.rec%40hra.nhs.uk%7C98672af6bb0b42130f3608de7858af65%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639080519460234190%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=n9EXnnGvHo7IGrD4dAuthVBH8iD46NQYARxvniV9yDY%3D&reserved=0
Use the study number 2023-507977-16-00 to search for more information on this website.
REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
21/EM/0102
Date of REC Opinion
9 Jun 2021
REC opinion
Further Information Favourable Opinion