Paroxysmal Nocturnal Hemoglobinuria (PNH)
This is a Phase 1b, single‑arm, open‑label study designed to evaluate the safety and tolerability of APL‑3007 in adults with paroxysmal nocturnal hemoglobinuria (PNH). Eligible participants receive a single dose of APL‑3007 administered in addition to their ongoing background therapy with a C5 inhibitor (ravulizumab‑cwvz). Participants must be on a stable dose of ravulizumab‑cwvz prior to study entry and continue this background therapy throughout the study. APL3007 is supplied as a sterile aqueous solution and administered as a single injection. The study includes one treatment arm only. There is no placebo or no‑treatment control group, and no randomisation is performed. All enrolled participants receive active treatment with APL‑3007 and are followed for safety and tolerability assessments after dosing. The planned study duration is approximately 6 months.
1. Participants must be 18 years or older at the time of signing the informed consent. 2. Participants must have a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH for short), have been treated for at least 6 months with the dose of ravulizumab-cwvz thought to have the best chance of controlling their disease but still show evidence of low hemoglobin below 10.5 g/dl. Also, they would have evidence abnormal breakdown of their blood cells leading to high count of reticulocytes more than the upper normal level, platelets being greater than 100 x 109/L, and total count of neutrophils being greater than 500/mm3. 3. Female participants must be either: 3.1. Women of who are not able to get pregnant, nonchildbearing potential, defined as women who have not seen their periods for at least 12 months after reaching menopause without applying an unnatural method to stop their periods. This also includes women who had surgery to remove both ovaries with or without the womb, or both fallopian tubes; and the surgery must have happened at least 6 weeks before being screened for the study. For those who had their ovaries removed there would be need to have on record that lab tests to check on the hormone levels were performed as a measure to confirm that she is no longer able to get pregnant. 3.2. Women who can get pregnant, defined as any women who have had their first menstrual period but have not used any method that makes it impossible for them to get pregnant or who have reached menopause. Such women must have a negative blood pregnancy test when screened for inclusion into the study and must agree to use methods that help prevent a woman from getting pregnant as defined in the protocol for this study ((Section 10.3.5.1) for the duration of the study and also agree to not breastfeed their babies during the entire period of the study. 4. Participants must have written evidence of vaccination against Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, and Y
1. The person can't take certain medicines that affect part of the immune system called the complement system. This includes drugs like rituximab and belimumab, or any other similar medicine even if it's still being tested unless it's a drug called ravulizumab-cwvz. They must stop taking those medicines long enough before the study starts so the medicine is mostly out of their body. 2. Participant has received a live vaccination (excluding seasonal flu vaccination) within 30 days before being given the study drug APL-3007. 3. Participant has received APL-3007 in the past. 4. The person has had any serious health problems like issues with their stomach, kidneys, liver, lungs, brain, heart, hormones, blood, allergies, or cancer that the doctor thinks could make it unsafe for them. 5. The person has liver damage, like liver scarring (called cirrhosis), or any other liver problem that could make it more likely for the medicine to hurt their liver 6. The person has or had an autoimmune disease that affects the whole body, unless they have Hashimoto’s thyroiditis and it’s well controlled 7. The person had an allergic reaction or serious side effects from a type of treatment called small interfering RNA therapy, or if they’re allergic to anything in the drug APL-3007. 8. The person has or had cancer, unless it was a type of skin cancer called basal cell or squamous cell, and it was treated successfully at least 2 years before joining the study 9. If it is hard to find a vein for drawing blood, or if they have skin problems, tattoos, dark spots, or bumps in the area where the shot will be given that could make it hard to give the shot or check the skin afterward. 10. The person has a health problem or is getting treatment for one that could affect how the study is done or make it unsafe for them, according to the doctor in charge. 11. The person has a medical or mental health condition that might make it hard for them to keep up with study visits or could make it unsafe for