This study has been transitioned to CTIS with ID 2024-511067-29-00 check the CTIS register for the current data. The purpose of the study is to evaluate the efficacy and safety of LNP023 compared to placebo on proteinuria reduction and slowing renal…
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective at the time of interim analysis is:
To demonstrate superiority of LNP023 vs. placebo in the reduction of
proteinuria at 9 months by measuring UPCR sampled from a 24h urine collection.
The primary objective at the time of final analysis is:
To demonstrate superiority of LNP023 vs. placebo in slowing IgAN progression
measured by the annualized total slope of eGFR decline over 24 months.
The primary clinical questions of interest at the Interim and Final Analysis
respectively are:
What is the treatment effect of LNP023 (200 mg b.i.d oral administration) vs.
placebo on
a) proteinuria reduction as measured by UPCR (sampled from 24h urine
collection) at the Interim analysis, and
b) slowing IgAN progression as measured by the annualized total eGFR slope at
the Final analysis
In primary IgAN patients with eGFR >= 30 mL/min/1.73m2 who are on background
ACEi/ARB treatment, as though corticosteroids, immunosuppressant therapy, or
other newly approved drugs or new background therapy for IgAN and Kidney
Replacement Therapy (KRT) were not available and regardless of unforeseen
changes in permitted/concomitant medications or treatment discontinuation for
any reason.
Secondary outcome
The secondary objectives at the time of interim analysis are:
To evaluate the effect of LNP023 vs. placebo on slowing eGFR decrease as
measured by the change from baseline in eGFR at 9 months.
To assess the effect of LNP023 vs. placebo on the proportion of study
participants reaching proteinuria below 1g/g of UPCR (sampled from
24h urine collection) at 9 months.
To evaluate the effect of LNP023 vs. placebo on slowing IgAN progression
measured by the annualized total slope of eGFR decline over 1 year.
To assess the effect of LNP023 vs. placebo on the change from baseline to 9
months in the fatigue scale measured by the Functional Assessment Of Chronic
Illness Therapy (FACIT-Fatigue) questionnaire.
To evaluate the safety and tolerability of LNP023 vs. placebo.
The secondary objectives at the time of final analysis are:
To demonstrate superiority of LNP023 vs. placebo in the reduction of
proteinuria at 9 months by measuring UPCR sampled from a 24h urine collection.
To demonstrate the superiority of LNP023 vs. placebo on the proportion of study
participants reaching proteinuria below 1g/g of UPCR (sampled from 24h urine
collection) at 9 months.
To demonstrate the superiority of LNP023 vs. placebo on delaying the time to
first occurrence of a composite kidney failure endpoint of reaching either at
least 30% decline in eGFR, eGFR <15 mL/min/1.73 m2, dialysis, kidney
transplantation or death from kidney failure.
To demonstrate the superiority of LNP023 vs. placebo on the change from
baseline to 9 months in the fatigue scale measured by FACIT-Fatigue
questionnaire.
To evaluate the safety and tolerability of LNP023 vs. placebo.
Background summary
The study is designed as a multicenter, randomized , double-blind, placebo
controlled study to demonstrate the superiority of LNP023 at a dose of 200 mg
b.i.d. compared to placebo on top of maximally tolerated or maximal locally
approved ACEi or ARB on reduction of proteinuria and slowing renal disease
progression in primary IgAN patients. The Kidney Disease Improving Global
Outcomes (KDIGO) guidelines recommend long-term supportive therapy with an ACEi
or ARB with or without high dose CS or IS for blood pressure control and
proteinuria reduction. In this double-blind, randomized study, the efficacy and
safety of LNP023 will be assessed in comparison to placebo on top of the
maximally tolerated or maximal locally approved doses of an ACEi or ARB.
Study objective
This study has been transitioned to CTIS with ID 2024-511067-29-00 check the CTIS register for the current data.
The purpose of the study is to evaluate the efficacy and safety of LNP023
compared to placebo on proteinuria reduction and slowing renal disease
progression in primary IgAN patients
Study design
This is a multi-center, randomized, double-blinded, placebocontrolled study,
which comprises a screening visit, followed by a run in period of 14 to
approximately 90 days. Thereafter, eligible participants will be randomized in
a 1:1 ratio to either LNP023 200mg or matching placebo b.i.d. for a 24 month
treatment period.
Intervention
Study participants will be randomized to LNP023 200 mg b.i.d. or placebo in 1:1
ratio, while
remaining on the maximally tolerated or locally approved maximal daily doses of
ACEi or ARB
throughout the treatment period.
Study burden and risks
The study lasts 24 to 27 months. The study starts with a screening period
followed by a run-in phase of maximum 90 days. After that there is a treatment
period of about 24 months in which the research medication is used. Three
months after the last administration of the
research medication there is a final check, unless the patient immediately
switches to the Roll-over Extension protocol.
Assuming 13 visits, the load will be as follows:
Collection of 24-hour urine: 5x
Collecting First Morning Void: 12x
Blood and urine test: 13x
Measure weight, pulse, blood pressure and temperature: 13x
Measuring the length: 1x
Questionnaires: 6x
Physical examination: 4x
ECG: 3x
Pregnancy test: 3 times if participant is in fertile period.
Kidney biopsy (if needed): 1x
Optional:
Pharmacogenetics (1x blood collection)
Side effects of research medication and inconvenient research procedures.
Prohibited co-medication.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
• Male and female patients >= 18 years of age with an eGFR level and
biopsy-confirmed IgA nephropathy as follows
o For patients eGFR* >= 45mL/min/1.73m2, a qualifying biopsy performed within
the last 5 years is required
o For patients with eGFR* 30 to <45mL/min/1.73m2, a qualifying biopsy performed
within 2 years with < 50% tubulointerstitial fibrosis is required
o For patients with eGFR* 20 to <30mL/min/1.73m2, a qualifying biopsy performed
at any time. In all cases, if a historical biopsy is not available, one may be
performed during screening.
• 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 and Streptococcus pneumoniae
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 Haemophilus influenzae
infection should be given, if available and according to local regulations, at
least 2 weeks prior to first study drug administration.
• 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 approximately 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 approximately 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.
• 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.
Participants previously or currently treated with oral budesonide. Participants
treated with endothelin (receptor) antagonists within 90 days prior to first
study drug administration.
• Prior use of LNP023 or prior enrollment in any other LNP023 clinical trial
where study drug was taken, including matching placebo
• History of recurrent invasive infections caused by encapsulated organisms,
such as meningococcus and pneumococcus.
• Active systemic bacterial, viral (including COVID-19) or fungal infection
within 14 days prior to study drug administration.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-511067-29-00 |
| EudraCT | EUCTR2020-001049-38-NL |
| ClinicalTrials.gov | NCT04578834 |
| CCMO | NL75457.056.20 |