A Phase 2 Study of Cemdisiran in Adult Patients with IgA Nephropathy
- Conditions
- Immunoglobulin A nephropathy (IgAN)Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2018-002716-27-SE
- Lead Sponsor
- Alnylam Pharmaceuticals Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
1. Male or female =18 years and =65 years of age at the time of informed consent
2. Clinical diagnosis of primary IgAN as demonstrated by historical biopsy collected within 60 months of screening
3. Treated for IgAN with stable, optimal pharmacological therapy. In general, stable and optimal treatment will include maximum allowed or tolerated ACE inhibitor or an ARB for at least 3 months prior to start of run-in period
4. Urine protein =1 g/24-hour at Screening from a valid 24-hour urine collection , and mean urine UP =1 g/24-hour from two valid 24-hour urine collections at the end of the run-in period, prior to randomization
5. Hematuria as defined by =10 RBCs per high powered field (RBC/hpf) by microscopy or a positive urine dipstick (2+[moderate] and above) measured by a central laboratory at screening
6. Females of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception 14 days before first dose, throughout study participation, and for 90 days after last dose administration
7. Previously vaccinated with meningococcal group ACWY conjugate vaccine and meningococcal group B vaccine or willingness to receive these vaccinations as well as prophylactic antibiotic treatment if required by local standard of care
8. Previously vaccinated or willingness to receive vaccinations for Hib and Streptococcus pneumoniae according to current national/local vaccination guidelines for vaccination use
9. Patient is willing and able to provide written informed consent and to comply with the study requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Concomitant significant renal disease other than IgAN
2. A diagnosis of rapidly progressive glomerulonephritis as measured by eGFR loss >30% over the duration of the run-in phase
3. Secondary etiologies of IgAN (eg, inflammatory bowel disease, celiac disease)
4. Diagnosis of Henoch-Schonlein Purpura (IgA Vasculitis)
5. eGFR <30 mL/min/1.73 m2 2 weeks prior to randomization (local results may be used for assessment of eligibility)
6. Has any of the following laboratory parameter assessments:
a. Alanine transaminase (ALT) >1.5×upper limit of normal (ULN), International Normalized Ratio (INR) >2 (or >3.5 if on anticoagulants), or total bilirubin >1.5×ULN (unless bilirubin elevation is due to Gilbert’s syndrome)
7. Confirmed positive IgG/IgM/IgA ADAs to cemdisiran at screening
8. Clinical laboratory test results considered clinically relevant and unacceptable in the opinion of the Investigator
9. Positive hepatitis B virus (HBV) surface antigen, HBV core antibody, hepatitis C virus (HCV) antibody (unless HCV viral load demonstrated negative)
10. Treatment with systemic steroids for more than 7 days or other immunosuppressant agents in the 6 months prior to randomization
11. Treatment with dual RAS blockade in the 3 months prior to entry into the run-in phase
12. Received an investigational agent within the last 30 days or 5 half-lives, whichever is longer, prior to the first dose of study drug, or are in follow-up of another clinical study prior to study enrollment
13. Known human immunodeficiency virus (HIV) infection, HCV infection or HBV infection
14. Malignancy (except for non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate cancer) within the last 5 years
15. Active psychiatric disorder, including, but not limited to schizophrenia, bipolar disorder, or severe depression despite current pharmacological intervention
16. Known medical history or evidence of chronic liver disease or cirrhosis
17. Has other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
18. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc
19. History of intolerance to SC injection(s) or significant abdominal scarring that could potentially hinder study drug administration or evaluation of local tolerability
20. Known contraindication to meningococcal vaccines (group ACWY conjugate and group B vaccines) required for this study. Refer to the most recent local product information for each vaccine for the current list of contraindications
21. Unable to take antibiotics for meningococcal prophylaxis, if required by local standard of care
22. Sustained blood pressure >140/90 mmHg as defined by 2 or more readings during the run-in period, measured in supine position after 10 minutes of rest
23. Receipt of an organ transplant (including hematologic transplant)
24. History of meningococcal infection within 12 months before Screening
25. Patients with systemic bacterial or fungal infections, that require systemic treatment with antibiotics or antifungals
26. Patients with functional or anatomic asplenia
27. Patients who consume more than 14 units of alcohol a week (unit 1 glass of wine [125 mL] = 1 measure of spirits [approximately 1 fluid ounce] = ½ pint of beer [approximately 284 mL])
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of cemdisiran on proteinuria in adult patients with immunoglobulin A nephropathy (IgAN);Secondary Objective: 1. To evaluate the effect of cemdisiran on additional measures of proteinuria in adult patients with IgAN<br>2. To evaluate the effect of cemdisiran on hematuria in adult patients with IgAN<br>3. To evaluate the safety and tolerability of cemdisiran<br>;Primary end point(s): Percent change from baseline in urine protein/creatinine ratio [UPCR] as measured in 24 hour urine ;Timepoint(s) of evaluation of this end point: Week 32
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Percent change from baseline in 24-hour proteinuria (g/24-hours)<br>2. Percent of patients with partial clinical remission (urine protein [UP] <1.0 g/24-hours) <br>3. Percent of patients with >50% reduction in 24-hour proteinuria <br>4. Change from baseline in UPCR as measured in a spot urine <br>5. Change from baseline in hematuria <br>6. Frequency of AEs<br>;Timepoint(s) of evaluation of this end point: Week 32