Clinical Trials List
Protocol NumberALN-CC5-005
NCT Number(ClinicalTrials.gov Identfier)NCT03841448
2019-06-15 - 2023-09-14
Phase II
Recruiting6
ICD-10D80.2
Selective deficiency of immunoglobulin A [IgA]
ICD-9279.01
Selective IgA immunodeficiency
A Phase 2, Randomized, Double-blind, Placebo-controlled Study of Cemdisiran in Adult Patients With IgA Nephropathy
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Alnylam Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 李隆志 Division of Nephrology
- 李岳庭 Division of Nephrology
- 鄭本忠 Division of Nephrology
- 邱千華 Division of Nephrology
- Wen-Chin Lee Division of Nephrology
- Chien-Hsing Wu Division of Nephrology
- 賴育城 Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Kun-Hua Tu Division of Nephrology
- Ya-Chung Tian Division of Nephrology
- 楊皇煜 Division of Nephrology
- HSIANG-HAO HSU Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 吳軍毅 Division of Nephrology
- CHENG-HSU CHEN Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Heng-Chih Pan Division of Nephrology
- 許恆榮 Division of Nephrology
- 陳國書 Division of Nephrology
- Chun-Yu Chen Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- VIN-CENT Wu Division of Nephrology
- 黃道民 Division of Nephrology
- 林裕峰 Division of Nephrology
- 楊紹佑 Division of Nephrology
- CHUN-FU LAI Division of Nephrology
- Jenq-Wen Huang Division of Nephrology
- - - Division of Nephrology
- 陳怡婷 Division of Nephrology
- SHUEI-LIONG LIN Division of Nephrology
- WEN-CHIH CHIANG Division of Nephrology
- - - Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
IgA Nephropathy
Objectives
Primary
To evaluate the effect of cemdisiran
on proteinuria in adult patients with
immunoglobulin A nephropathy
(IgAN)
Secondary
To evaluate the effect of cemdisiran
on remission of proteinuria in adult
patients with IgAN
To evaluate the effect of cemdisiran
on hematuria in adult patients with
IgAN
To evaluate the safety and tolerability
of cemdisiran
Exploratory
To evaluate the effect of cemdisiran
on renal function parameters
To evaluate the pharmacodynamic
(PD) effect of cemdisiran in adult
patients with IgAN
To characterize the pharmacokinetics
(PK) of cemdisiran and relevant
metabolites in plasma and urine in
adult patients with IgAN
To evaluate the effect of cemdisiran
on serum and urine markers of
complement activation, renal damage
and inflammation
To assess the incidence of antidrug
antibodies (ADA)
Test Drug
Cemdisiran (ALN-CC5)
Active Ingredient
Cemdisiran (ALN-CC5)
Dosage Form
SC
Dosage
200
Endpoints
Primary Outcome Measures :
Percentage Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) as Measured in 24-hour Urine at Week 32 [ Time Frame: Baseline, Week 32 ]
Secondary Outcome Measures :
Percent Change from Baseline in 24-Hour Proteinuria at Week 32 [ Time Frame: Baseline, Week 32 ]
Percentage of Participants with Partial Clinical Remission at Week 32 [ Time Frame: Week 32 ]
Percentage of Participants with >50% Reduction in 24-hour Proteinuria at Week 32 [ Time Frame: Week 32 ]
Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) as Measured in a Spot Urine at Week 32 [ Time Frame: Baseline, Week 32 ]
Change From Baseline in Hematuria at Week 32 [ Time Frame: Baseline, Week 32 ]
Frequency of Adverse Events (AEs) [ Time Frame: Up to Week 240 ]
Percentage Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) as Measured in 24-hour Urine at Week 32 [ Time Frame: Baseline, Week 32 ]
Secondary Outcome Measures :
Percent Change from Baseline in 24-Hour Proteinuria at Week 32 [ Time Frame: Baseline, Week 32 ]
Percentage of Participants with Partial Clinical Remission at Week 32 [ Time Frame: Week 32 ]
Percentage of Participants with >50% Reduction in 24-hour Proteinuria at Week 32 [ Time Frame: Week 32 ]
Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) as Measured in a Spot Urine at Week 32 [ Time Frame: Baseline, Week 32 ]
Change From Baseline in Hematuria at Week 32 [ Time Frame: Baseline, Week 32 ]
Frequency of Adverse Events (AEs) [ Time Frame: Up to Week 240 ]
Inclution Criteria
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 ≥1g/24-hour at screening and mean urine protein ≥1g/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) at screening and
either ≥10 RBC/hpf or a positive urinary dipstick (1+ and above) at the end of the run-in
period, prior to randomization (local result accepted for assessment of eligibility at the
end of the run-in period)
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
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 ≥1g/24-hour at screening and mean urine protein ≥1g/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) at screening and
either ≥10 RBC/hpf or a positive urinary dipstick (1+ and above) at the end of the run-in
period, prior to randomization (local result accepted for assessment of eligibility at the
end of the run-in period)
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
Exclusion Criteria
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 will 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. Known human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV)
infection or hepatitis B virus (HBV) infection
10. Treatment with systemic steroids at dosages exceeding 20 mg prednisone-equivalent for
more than 7 days or other immunosuppressant agents in the 12 months prior to
randomization
11. 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
12. 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
13. Active psychiatric disorder, including, but not limited to schizophrenia, bipolar disorder,
or severe depression despite current pharmacological intervention
14. Known medical history or evidence of chronic liver disease or cirrhosis
15. Has other medical conditions or comorbidities which, in the opinion of the Investigator,
would interfere with study compliance or data interpretation
16. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or
GalNAc
17. History of intolerance to SC injection(s) or significant abdominal scarring that could
potentially hinder study drug administration or evaluation of local tolerability
18. 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
19. Unable to take antibiotics for meninigococcal prophylaxis, if required by local standard
of care
20. 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
21. Receipt of an organ transplant (including hematologic transplant)
22. History of meningococcal infection within 12 months before Screening
23. Patients with systemic bacterial or fungal infections that require systemic treatment with
antibiotics or antifungals
24. Patients with functional or anatomic asplenia
25. 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])
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 will 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. Known human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV)
infection or hepatitis B virus (HBV) infection
10. Treatment with systemic steroids at dosages exceeding 20 mg prednisone-equivalent for
more than 7 days or other immunosuppressant agents in the 12 months prior to
randomization
11. 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
12. 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
13. Active psychiatric disorder, including, but not limited to schizophrenia, bipolar disorder,
or severe depression despite current pharmacological intervention
14. Known medical history or evidence of chronic liver disease or cirrhosis
15. Has other medical conditions or comorbidities which, in the opinion of the Investigator,
would interfere with study compliance or data interpretation
16. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or
GalNAc
17. History of intolerance to SC injection(s) or significant abdominal scarring that could
potentially hinder study drug administration or evaluation of local tolerability
18. 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
19. Unable to take antibiotics for meninigococcal prophylaxis, if required by local standard
of care
20. 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
21. Receipt of an organ transplant (including hematologic transplant)
22. History of meningococcal infection within 12 months before Screening
23. Patients with systemic bacterial or fungal infections that require systemic treatment with
antibiotics or antifungals
24. Patients with functional or anatomic asplenia
25. 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])
The Estimated Number of Participants
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Taiwan
20 participants
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Global
30 participants
