Resumen

Estudio para investigar el impacto del tratamiento con iptacopan sobre la inmunopatología subyacente en pacientes con nefropatía por IgA (IgAN), mediante la evaluación de cambios en marcadores clínicos y moleculares clave desde el inicio hasta los 9 meses. El estudio tiene como objetivo aportar información sobre los aspectos sistémicos y específicos del riñón del tratamiento, cuantificando el cambio en el depósito de fragmentos que contienen C3c mesangial como indicador de la activación del complemento, y evaluando una variedad de biomarcadores relacionados con la función renal, el daño y la progresión de la enfermedad, incluyendo, entre otros, la puntuación Oxford MEST-C.

Descripción detallada

El estudio comprende un período de cribado seguido de una visita basal, en la que se realizará una biopsia renal basal. Los participantes elegibles incluidos en el estudio recibirán iptacopan 200 mg dos veces al día durante un período de tratamiento de 9 meses. No se permite el ajuste de dosis de iptacopan durante el período de tratamiento. Al mes 9, tras completar el período de tratamiento, se realizará una biopsia de seguimiento a todos los participantes en el momento del fin del estudio (EOS).

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 99 YearsSexo: ALL

Criterios de inclusión

Signed informed consent must be obtained prior to participation in the study; participants should be able to communicate well with the investigator, understand and comply with the requirements of the study.
Male and female participants ≥18 years of age with biopsy-confirmed IgA nephropathy and an eGFR ≥ 30 mL/min/1.73m2. eGFR will be calculated using the CKD-EPI 2009 formula.
Proteinuria as assessed at screening by UPCR ≥ 0.8g/g or 1g/d sampled from FMV.
Biopsy at baseline should confirm IgAN with \< 50% tubulointerstitial fibrosis.
Participants must be on ACEi or ARB treatment at either the locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgment) for approximately 90 days prior to baseline visit and continue on a stable dose throughout the study. Participants with allergies or intolerance to ACEi and ARB are eligible for the study, but the investigator should clearly document the reasons for not being on maximal ACEi/ARB dose in the source documents. In addition, if participants are taking diuretics, other antihypertensive medication or Sodium-Glucose Co-Transporter 2 inhibitors (SGLT2i), the doses should be stabilized for at least 90 days prior to baseline.
Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections required to be completed at least 2 weeks prior to the start of study treatment. If the participants have 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 must start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated.
Vaccination against Haemophilus influenzae infection should be given, if available and according to local regulations, at least 2 weeks prior to first study drug administration.

Criterios de exclusión

Any secondary IgAN (at historic or baseline biopsies) as defined by the investigator and IgA vasculitis Henoch-Scholein Purpura (HSP). 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.
Any secondary diagnosis at baseline biopsy (other than IgA nephropathy).
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 screening visit.
Participants treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, systemic corticosteroids exposure (\>7.5 mg/d prednisone/prednisolone equivalent) or targeted release formulation (TRF) of budesonide within 90 days (or 180 days for rituximab) prior to first study drug administration. Participants using other medication such us hydroxychloroquine or Endothelin receptor antagonists (ERAs).
Use of other investigational drugs within 5 half-lives or within 30 days of enrollment, whichever is longer.
Prior use of iptacopan or prior enrollment in any other iptacopan clinical trial where study drug was taken, including matching placebo.
All transplanted participants (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 participant's participation in the study or that will require the use of prohibited medications.
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 positive HBsAg in conjunction with core antibody (anti-HBc), or HCV-RNA positive at screening, or liver injury as indicated by abnormal liver function tests at screening 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 agree to use 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, post ovulation 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 months prior to screening) of male partner of the female 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.
If local regulations are more stringent than the contraception methods listed above, local regulations apply and will be described in the ICF.
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 childbearing 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 childbearing potential.
If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.

Estudio multicéntrico, de brazo único, abierto, con biopsia, para evaluar los cambios estructurales y funcionales en los riñones de pacientes adultos con nefropatía por IgA que reciben iptacopan además del tratamiento de soporte

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Iptacopan

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores

Contactos

Novartis Pharmaceuticals

Novartis Pharmaceuticals