Ensayos clínicos

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study; patients should be able to communicate well with the investigator, understand and comply with the requirements of the study.
• Male and female patients, ≥ 18 years of age.
• Having an eGFR level and biopsy-confirmed IgA nephropathy as follows:
  • For patients eGFR* ≥ 45mL/min/1.73m^2 , a qualifying biopsy performed within the last 5 years is required;
  • For patients with eGFR* 30 to <45mL/min/1.73m^2 , a qualifying biopsy performed within 2 years with < 50% tubulointerstitial fibrosis is required;
  • For patients with eGFR* 20 to <30mL/min/1.73m^2 , a qualifying biopsy performed at any time. In all cases, if a historical biopsy is not available, one may be performed during screening. *eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines).
• Proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening by UPCR ≥ 1 g/g (113 mg/mmol) sampled from FMV or 24h urine collection, as well as at the completion of the run-in period by UPCR ≥1 g/g (113 mg/mmol) calculated as the (geometric) mean of two 24h urine collections obtained within 14 days of each other at baseline.
• Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
• If not previously vaccinated, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
• All patients must have been on supportive care including stable dose regimen of ACEi or ARB at either the locally approved maximal daily dose or the maximally tolerated dose (per investigators’ judgment) for at least 90 days before first study drug administration. In addition, if patients are taking diuretics, other antihypertensive medication, or other background medication for IgAN, the doses should also be stabilized for at least 90 days prior to the first dosing of study treatment.

Exclusion Criteria:

• Any secondary IgAN as defined by the investigator; secondary IgAN can be associated with cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, dermatitis herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, and inflammatory bowel disease, familial mediterranean fever, etc.
• Evidence of significant urinary obstruction or difficulty in voiding; any urinary tract disorder other than IgAN at screening and before first study drug administration.
• Current or planned usage of any homeopathic and/or herbal medications for IgAN disease progression, such as but not limited to Lei Gong Teng.
• Current acute kidney injury (AKI) defined by Acute Kidney Injury Network (AKIN) criteria within 4 weeks of screening.
• Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to screening, or presence of nephrotic syndrome.
• Sitting office SBP > 140 mmHg or DBP > 90 mmHg at the randomization visit.
• Patients previously treated with immunosuppressive or other immunmodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids exposure (> 7.5 mg/d prednisone/prednisolone equivalent) within 90 days (or 180 days for rituximab) prior to first study drug administration.
• Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days, whichever is longer.
• Prior use of LNP023 or prior enrollment in any other LNP023 clinical trial where study drug was taken, including matching placebo.
• All transplanted patients (any solid organ transplantation, including bone marrow transplantation).
• History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.
• Major concurrent comorbidities including but not limited to advanced cardiac disease (e.g., New York Heart Association (NYHA) class IV), severe pulmonary disease (e.g., severe pulmonary hypertension (World Health Organization (WHO) class IV)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes participant's participation in the study.
• Any medical condition deemed likely to interfere with the patient’s participation in the study.
• Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study drug administration.
• Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration.
• Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening).
• History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
• Liver disease, such as active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection defined as HBsAg positive or HCV-RNA positive at screening, or liver injury as indicated by abnormal liver function tests at screening and baseline as defined below:
  • Any single parameter of ALT, AST, GGT, alkaline phosphatase must not exceed 3 × upper limit of normal (ULN);
  • Serum bilirubin must not exceed 2 × ULN.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer treated with curative intent), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of investigational drug and for 1 week after stopping of investigational drug. Effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception;
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
  • Male sterilization (at least 6 m prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant;
  • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/vaginal suppository;
  • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS);
  • In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms). Women are considered not of child bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.

Eligibility last updated 12/10/21. Questions regarding updates should be directed to the study team contact.