To evaluate the efficacy of danicopan as compared to placebo as add-on therapy to a C5 inhibitor at 12 weeks.
ID
Source
Brief title
Condition
- Red blood cell disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change From Baseline In Hemoglobin (Hgb)
Secondary outcome
* Percentage Of Participants With Transfusion Avoidance
* Change From Baseline In Functional Assessment Of Chronic Illness Therapy
(FACIT) Fatigue Scores; Scoring 0-52
* Change From Baseline In Absolute Reticulocyte Count
Background summary
PNH is a rare blood disease in which red blood cells are attacked by a part of
the body*s immune system known as the complement system. People with PNH
produce red blood cells without key immune proteins attached. Without these
immune proteins, the complement system recognizes the red blood cells as a
threat and destroys them throughout the body. The destruction of red blood
cells is largely responsible for many of the symptoms of PNH and causes anemia.
Currently, C5 inhibitors are the only approved treatment for PNH. C5 inhibitors
work by suppressing the activity of a specific portion of the complement
system. Some patients on approved C5 inhibitor therapies may continue to have
anemia.
This study looks at an investigational drug called ALXN2040. This drug is being
developed to treat PNH by blocking a protein called factor D in the complement
system. By blocking factor D, ALXN2040 may help further treat PNH in patients
currently receiving a C5 inhibitor but this is not yet proved. This study will
determine if ALXN2040 (danicopan), when used with a C5 inhibitor, improves
anemia in patients with PNH.
Study objective
To evaluate the efficacy of danicopan as compared to placebo as add-on therapy
to a C5 inhibitor at 12 weeks.
Study design
This is a multiple-region, randomized, double-blind, placebo-controlled,
multiple-dose, Phase 3 study in patients with PNH who have clinically evident
EVH on a C5 inhibitor (eculizumab or ravulizumab).
Intervention
Treatment Period 1 * The patient will receive either placebo or ALXN2040 (1:2
chance) orally three times a day for 12 weeks.
Treatment Period 2 * The patient will receive ALXN2040 orally three times a day
for 12 weeks.
Long Term Extension * The patient will receive ALXN2040 orally three times a
day for 52 weeks.
Study burden and risks
Subject*s participation in this study will last up to 18 months and consists of
a 24-week study period and the 52-week long-term extension. This includes up to
35 visits (20 to the study center, 15 have the potential to be completed at
home using a visiting healthcare service). Aside from the intervention
described above, participation in this study involves blood draws at multiple
visits. Participants will be subjected to questions regarding medical history,
concomitant medications, vaccination history and adverse events; urine
sampling; pregnancy tests; measurement of vital signs; physical examination;
ECGs and patient reported outcomes and quality of life questionnaires.
Subjects will be expected to take the IP as explained, not take part in other
medical studies, keep their appointments for visits, monitor their temperature
daily at home and seek emergency medical attention if needed, not discuss
information about the study in public places while the study is in progress,
keep a patient card with them at all times, not donate blood/sperm/ova and use
appropriate forms of contraception.
In 266 healthy volunteers, the most commonly experienced side effects
(experienced by 5 or more subjects) included: headache, nausea (a feeling of
wanting to vomit), throat irritation, nasal congestion, upper respiratory tract
infection, feeling hot, indigestion, bruising, diarrhea, stomach inflammation,
abdominal discomfort or pain, muscle pain, increase in blood creatine
phosphokinase (a marker of muscle injury), throat discomfort, and dizziness or
feeling faint. The majority of events were mild.
However, PNH is a serious, life-threatening disease, and there are unmet needs
in this population that are not addressed by an approved C5 inhibitor that
could potentially be addressed by an effective oral FD inhibitor.
Seaport Blvd 121
Boston MA 022101
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Seaport Blvd 121
Boston MA 022101
US
Listed location countries
Age
Inclusion criteria
* Diagnosis of PNH
* Clinically Evident EVH defined by:
- Anemia (Hgb *9.5 gram/deciliter) with absolute reticulocyte count * 120 x
10^9/liter.
- At least 1 packed red blood cell or whole blood transfusion within 6 months
prior to the start of the study.
* Receiving a C5 inhibitor for at least 6 months prior to Day 1
* Platelet count *30,000/microliters (*L)
* Absolute neutrophil counts *750/*L.
* Documentation of/or willingness to receive vaccinations and prophylactic
antibiotics as required.
Exclusion criteria
* History of a major organ transplant or hematopoietic stem cell
transplantation (HSCT).
* Known aplastic anemia or other bone marrow failure that requires HSCT or
other therapies including anti-thymocyte globulin and/or immunosuppressants.
* Known or suspected complement deficiency.
* Laboratory abnormalities at screening, including:
- Alanine aminotransferase >2 x ULN.
- Direct bilirubin >2 x ULN (unless due to EVH or documented Gilbert's Syndrome.
* Current evidence of biliary cholestasis.
* Estimated glomerular filtration rate <30 milliliters/minute/1.73 meter
squared and/or are on dialysis.
* Evidence of human immunodeficiency virus, hepatitis B, or active hepatitis C
infection at screening.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-003829-18-NL |
| ClinicalTrials.gov | NCT04469465 |
| CCMO | NL74809.056.20 |