Cemdisiran and eculizumab dose-ranging study for paroxysmal nocturnal haemoglobinuria
- Conditions
- Paroxysmal nocturnal haemoglobinuria (PNH)Haematological DisordersParoxysmal nocturnal haemoglobinuria [Marchiafava-Micheli]
- Registration Number
- ISRCTN31882639
- Lead Sponsor
- niversity of Leeds
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped
- Sex
- All
- Target Recruitment
- 9
Current participant inclusion criteria as of 30/07/2019:
1. Aged at least 18 years
2. Diagnosis of PNH and on eculizumab therapy for a minimum of 90 days at a stable dose (i.e. the dose of eculizumab has not changed in the previous 90 days)
3. Women of child-bearing potential1 (WOCBP) must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use a highly effective method of contraception 14 days before cemdisiran administration, throughout study participation, and for 6 months after cemdisiran administration
4. Male participants with partners that are WOCBP must use double-barrier contraception (male condom plus appropriate barrier method for the female partner) for 14 days before cemdisiran administration, throughout study participation, and for 6 months after cemdisiran administration. Male participants must not donate sperm while on treatment and for at least 6 months after last dose of cemdisiran
5. Willing and able to comply with the study requirements and to provide written informed consent
6. Vaccinated against Neisseria meningitidis according to standard practice
Previous participant inclusion criteria:
1. Aged at least 18 years
2. Diagnosis of PNH and on eculizumab therapy for a minimum of 90 days at a stable dose of 900mg (i.e. the dose of eculizumab has not changed in the previous 90 days)
3. Women of child-bearing potential1 (WOCBP) must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use a highly effective method of contraception 14 days before cemdisiran administration, throughout study participation, and for 6 months after cemdisiran administration
4. Male participants with partners that are WOCBP must use double-barrier contraception (male condom plus appropriate barrier method for the female partner) for 14 days before cemdisiran administration, throughout study participation, and for 6 months after cemdisiran administration. Male participants must not donate sperm while on treatment and for at least 6 months after last dose of cemdisiran
5. Willing and able to comply with the study requirements and to provide written informed consent
6. Vaccinated against Neisseria meningitidis according to standard practice
1. Alanine transaminase (ALT) =2 ×ULN, or total bilirubin =4×ULN (unless bilirubin elevation is due to Gilbert’s syndrome), and considered clinically relevant in the opinion of the Investigator
2. Spontaneous vascular thrombosis within 90 days of registration (patients may be rescreened)
3. History of bone marrow transplantation
4. Clinical laboratory test results considered clinically relevant and unacceptable in the opinion of the Investigator
5. Planned change in eculizumab dose within 90 days of administration of cemdisiran (patients may be rescreened)
6. Known or suspected hereditary asymptomatic complement deficiency
7. Known clinical laboratory evidence or clinical diagnosis of human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) infection, or chronic hepatitis B virus (HBV) infection as shown by hepatitis B surface antigen positivity in the blood
8. Presence or suspicion of active viral, bacterial, fungal, or parasitic infection within 14 days before cemdisiran administration (patients may be rescreened)
9. Travelled to Saudi Arabia or Africa within 90 days of Screening, or planning to do so during the study (patients may be rescreened)
10. Received a complement targeted investigational agent within 90 days prior to screening (or 5 half-lives) depending which is longer
11. In follow-up of another clinical trial before trial registration
12. Active serious mental illness or psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention
13. Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
14. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc)
15. History of intolerance to SC injection(s) or significant abdominal scarring that could potentially hinder study drug administration or evaluation of local tolerability
16. History of meningococcal infection within 12 months before screening
17. Known history or evidence of chronic liver disease, alcohol abuse or cirrhosis
18. Concomitant use of anticoagulants if not on a stable dose regimen for at least 2 weeks prior to screening
19. Significant aplasia e.g. neutrophils <0.5 x 10*9/l or platelets <30 x 10*9/l
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Disease control up to 8 weeks, defined by LDH =1.5 × upper limit of normal (ULN) maintained up to 8 weeks with treatment at allocated dose schedule, measured by blood results
- Secondary Outcome Measures
Name Time Method <br> 1. The changes in LDH in patients with PNH over the course of the study:<br> 1.1. LDH =1.5 × ULN maintained up to 36 weeks, measured by blood results<br> 1.2. LDH levels at each of the scheduled timepoints up to 36 weeks, measured by blood results<br> 2. The safety, tolerability and compliance of cemdisiran in combination with eculizumab administration:<br> 2.1. Incidence of adverse events (AEs), from consent until 28 days post last dose of trial treatment:<br> 2.1.1. Number of haemoglobinuria events, measured by blood results<br> 2.1.2. Number of transfusions per participant, reported by the participant<br> 2.2. Treatment compliance, measured throughout the study:<br> 2.2.1. Dose modifications to registered treatment schedule including reasons, reported by the research team<br>