ALN-CC5-005: A Phase 2, Randomized, Double-blind, Placebo-controlled Study of Cemdisiran in Adult Patients with IgA Nephropathy

  • STATUS
    Recruiting
Updated on 23 November 2020

Summary

This is a multicenter, double-blind, placebo-controlled study comprised of three periods  The first period of the study is an observational 14-week run-in period during which patients’ blood pressure, kidney function, degree of hematuria, and proteinuria will be measured.

Patients will not receive study drug (cemdisiran or placebo) during this time. The standard of care is expected to remain unchanged during this run-in period. The second study period is a 36-week treatment period which will evaluate the efficacy and safety of SC cemdisiran compared to SC placebo in combination with standard of care in patients with IgAN and persistent proteinuria. The third period of the study is a 52-week optional open-label extension (OLE) period to further evaluate the long-term safety and clinical activity of cemdisiran. During the OLE, all patients (including those initially on placebo) will be treated with cemdisiran in combination with standard of care.

The study will include Screening of up to 90 days to determine eligibility of patients and to complete disease-related assessments. Patients will provide written informed consent and visit the study center approximately 2 weeks before starting the run-in period to complete the protocol screening assessments. Following successful screening, the 14-week run-in period will commence, during which patients’ blood pressure, kidney function, degree of hematuria and proteinuria as well as treatment with standard of care will be documented by the Investigator.

 

Description

The standard of care is expected to remain unchanged during this run-in period. Patients whose proteinuria level remains >1 g/24-hours within 2 weeks of the end of the run-in period, who continue to have hematuria, and who meet blood pressure and eGFR criteria will be eligible to enroll in the 36-week treatment period. Upon confirmation of eligibility followed by vaccination against meningococcal infections, patients will be randomized at a 2:1 ratio to receive 600 mg of cemdisiran or placebo every 4 weeks in combination with standard of care.

Approximately 30 patients are planned to be randomized in total, 20 in the cemdisiran arm and 10 in the placebo arm. Patients excluded before randomization will be replaced at Screening.

During the run-in period, patients will visit the study center 14, 8, and 2 weeks prior to randomization (Weeks 0, 6 and 12 of the run-in period). Patients will then return to the study center every 4 weeks after the start of study drug treatment period. The primary endpoint will be assessed at the end of treatment at Week 32.

 

At the end of treatment (Week 32), patients in the two treatment arms will enter the optional OLE period where they will receive cemdisiran at a dose of 600 mg every 4 weeks in combination with standard of care for 52 weeks.

- The first study drug administration of the OLE will be administered at Week 36.

- Patients will return to the study center at Week 40 and every 8 weeks thereafter during the OLE.

- Home visits, where locally feasible, may be arranged for cemdisiran administration in between 8-weekly study center visits (Weeks 44, 52, 60, 68 and 76), unless patients are required to visit the study center as judged necessary by the Investigator, or if home visits cannot be arranged.

 

An end of treatment (EOT) visit will occur at Week 80 (OLE EOT) and an end of study (EOS) or early termination (ET) visit will be completed at Week 84 (OLE EOS/ET). For patients who complete the treatment period only who do not consent to continue to participate in the study in the OLE period, the EOS/ET visit will be at Week 36.

- Patients will return to the clinical study center for safety follow-up visits approximately 13, 26, 39 and 52 weeks after the EOS/ET visit (regardless if EOS/ET visit is at Week 36 or Week 84), unless enrolled in another study with cemdisiran.

- Home visits, where locally feasible, may be arranged during safety follow-up at 13 and 39 weeks after the EOS/ET visit (regardless if EOS/ET visit is at Week 36 or Week 84).

 

Regular reviews of safety and tolerability data will be performed by an independent data monitoring committee (DMC) throughout the study with the primary purpose of protecting the safety of participating patients and the integrity of the study 24 hour urine collections.

 

Duration of Study The maximum estimated total time on study, inclusive of Screening (maximum of 90 days), run-in period (14 weeks), treatment period (36 weeks), optional OLE period (52 weeks) and safety follow-up (52 weeks), is approximately 36 months or 3.0 years.
    - This is an open label study. - Lab done for the study which maybe difficult to have done through insurance.

Details
Condition Proteinuria, Kidney Disease
Clinical Study IdentifierTX227889
Last Modified on23 November 2020

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 65 yrs?
Gender: Male or Female
Do you have any of these conditions: Proteinuria or Kidney Disease?
Patients are eligible to be included in the study if all the following criteria apply
Age and Sex
Male or female ≥18 years and ≤65 years of age at the time of informed consent
Patient and Disease Characteristics
Clinical diagnosis of primary IgAN as demonstrated by historical biopsy collected within 60 months of screening
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
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
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)
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
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
Previously vaccinated or willingness to receive vaccinations for Hib and Streptococcus pneumoniae according to current national/local vaccination guidelines for vaccination use
Informed Consent
Patient is willing and able to provide written informed consent and to comply with the study requirements 4.2

Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply
Disease-specific Conditions
Concomitant significant renal disease other than IgAN
A diagnosis of rapidly progressive glomerulonephritis as measured by eGFR loss >30% over the duration of the run-in phase
Secondary etiologies of IgAN (eg, inflammatory bowel disease, celiac disease)
Diagnosis of Henoch-Schonlein Purpura (IgA Vasculitis)
eGFR <30 mL/min/1.73 m2 2 weeks prior to randomization (local results will be used for assessment of eligibility)
Laboratory Assessments
Has any of the following laboratory parameter assessments
a. Alanine transaminase (ALT) >1.5×upper limit of normal (ULN)
b. International Normalized Ratio (INR) >2 (or >3.5 if on anticoagulants), or
c. total bilirubin >1.5×ULN (unless bilirubin elevation is due to Gilbert’s syndrome)
Confirmed positive IgG/IgM/IgA ADAs to cemdisiran at Screening
Clinical laboratory test results considered clinically relevant and unacceptable in the opinion of the Investigator
Known human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) infection or hepatitis B virus (HBV) infection
Prior/Concomitant Therapy
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
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
Medical Conditions
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
Active psychiatric disorder, including, but not limited to schizophrenia, bipolar disorder, or severe depression despite current pharmacological intervention
Known medical history or evidence of chronic liver disease or cirrhosis
Has other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc
History of intolerance to SC injection(s) or significant abdominal scarring that could potentially hinder study drug administration or evaluation of local tolerability
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
Unable to take antibiotics for meninigococcal prophylaxis, if required by local standard of care
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
Receipt of an organ transplant (including hematologic transplant)
History of meningococcal infection within 12 months before Screening
Patients with systemic bacterial or fungal infections that require systemic treatment with antibiotics or antifungals
Patients with functional or anatomic asplenia
Alcohol Use
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])
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