ACH-0144471 in PNH patients with inadequate response to eculizumab
Research type
Research Study
Full title
A Phase 2 Open-label Study of ACH-0144471 in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy
IRAS ID
243614
Contact name
Austin Kulasekararaj
Contact email
Sponsor organisation
Alexion Europe SAS
Eudract number
2016-003526-16
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
U111-1209-4655, UTN; 127,367, IND
Duration of Study in the UK
3 years, 7 months, 13 days
Research summary
This study is being done to find out how safe and effective the study drug ACH-0144471 is at controlling the complement system by inhibiting Factor D, in patients with paroxysmal nocturnal haemoglobinuria (PNH) who have had an inadequate response to eculizumab.
The complement system is found in the blood and helps or “complements” the ability of the body to get rid of many disease-causing organisms. It is part of the body’s defence system. Many diseases are associated with either an inefficient control of complement or too much activity of the complement system. Factor D is one of the proteins within the complement system and the sponsor (Alexion Pharmaceuticals Inc.) believes that blocking this protein will help treat certain diseases, affecting the complement system, such as PNH.
This study will determine if ACH-0144471 given in combination with eculizumab is effective in increasing the haemoglobin (protein in the red blood cell that carries oxygen) in the blood after 24 weeks of treatment and reducing blood transfusions. Eculizumab, a drug that the patient is already taking for PNH, acts by blocking some complement proteins in the blood other than Factor D. Some patients treated with eculizumab have only a partial improvement in their PNH and continue to require blood transfusions.Following a screening period of up to 60 days (including vaccinations, when applicable), eligible patients will enter the treatment portion of the study.
All patients will receive daily oral doses of ACH-0144471 three times a day plus eculizumab according to the patient’s usual dose and schedule for a total of 24 weeks. After Week 24, if the patient is receiving clinical benefit (as assessed by the investigator) they can continue with treatment in an extension phase.This study will include 12 patients with PNH who are currently receiving eculizumab treatment from multiple centres globally.
Lay summary of study results: The researchers wanted to see how effective danicopan was when given in addition to eculizumab in improving the participants’ anemia after 24 weeks of combined treatment. To answer this question, the researchers measured the increase in the blood levels of hemoglobin (the protein contained in red blood cells which carries oxygen around the body) from the start of the study (baseline) to the end of the Treatment Period (24 weeks).
What was the increase in the blood levels of hemoglobin from baseline to the end of the Treatment Period (24 weeks)?
On average, the blood levels of hemoglobin increased by 2.39 grams per deciliter (g/dL).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 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 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, 8 out of 12 participants (66.7%) had serious side effects during the overall study (Treatment Period + Extended Treatment Period), the majority of which were thought by study doctors to not be related to danicopan.A total of 1 out of 12 participants (8.3%) experienced a related serious side effect of fever.
None of the participants (0%) died during the study.
What side effects did participants have in this study?
Overall, 12 out of 12 participants (100%) had side effects during the overall study (Treatment Period + Extended Treatment Period), the majority of which were thought by study doctors to not be related to danicopan. A total of 4 out of 12 participants (33.3%) had a side effect that was thought by study doctors to be related to danicopan. The related side effects were:
immunization reaction (it may induce redness, swelling, and tenderness around the injection area, and fever), rapid heartbeat, fever, and increased levels of ALT (alanine aminotransferase, a liver enzyme) in the blood.Were there any other important safety findings in this study?
1 out of 12 participants (8.3%) stopped taking danicopan because of side effects not related to danicopan.How has this study helped participants and researchers?
The information collected in this study showed that danicopan was effective in treating adults with PNH when given with eculizumab; the addition of danicopan contributed to improving anemia in participants whose PNH was not adequately controlled when previously treated with eculizumab only. The results also showed that danicopan was safe and the majority of side effects were thought by study doctors to not be related to danicopan.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 danicopan or your treatment of PNH, please talk to your doctor. Danicopan is an experimental drug that has not yet received approval from the regulatory authorities for prescribed treatment. You should not change your treatment based on the results of this study without talking to a doctor first.
REC name
London - City & East Research Ethics Committee
REC reference
18/LO/0910
Date of REC Opinion
23 Jul 2018
REC opinion
Further Information Favourable Opinion