The purpose of this study is to ascertain the efficacy, safety, tolerability and pharmacokineticsof LNP023 over a 24-week treatment period compared with rituximab in subjects with MN.
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the efficacy of LNP023 compared with rituximab
Secondary outcome
Objective 1: To assess the safety and tolerability of dose of LNP023
Objective 2: To assess the relationship between LNP023 systemic
drug exposure and pharmacodynamics, mode-of-action markers
and clinical efficacy
Objective 3: To assess the effect of LNP023 compared with
rituximab on proteinuria remission and renal function
Objective 4: To assess the pharmacokinetics of LNP023
Background summary
Idiopathic (primary) membranous nephropathy (MN) is a glomerular disease in
40-70 year old adults very frequently associated with nephrotic syndrome and
significant morbidity, including the progressive loss of renal function leading
to End Stage Renal Disease (ESRD).
The estimated prevalence is around 550 per million, giving a total of
approximately 100,000 patients in the US and about twice
that in the EU. There is also evidence that the prevalence of MN is increasing
in certain regions,for example in China.
Current recommended therapies include the Ponticelli regimen (oral and
i.v.corticosteroids and alkylating agents) or calcineurin inhibitors, though
both of these are associated with significant adverse effects. There is
increasing use of the B-cell depleting
monoclonal antibody rituximab, though this agent is not licensed for this
indication and does not feature in any current treatment guidelines.
There is a high-unmet medical need for new therapies and therapies targeting
the complement system represent a promising approach.
Study objective
The purpose of this study is to ascertain the efficacy, safety, tolerability
and pharmacokinetics
of LNP023 over a 24-week treatment period compared with rituximab in subjects
with MN.
Study design
This is a randomized, treatment open-label, dose blinded, parallel group, three
arm proof-ofconcept,
non-confirmatory study evaluating the efficacy and safety of LNP023 compared
with
rituximab in subjects with MN at high risk of disease progression defined on
the basis of anti-
PLA2R antibody titre (>= 60 RU/mL) and proteinuria (>= 3.5 g/24h)
Intervention
LNP023 or rituximab
Study burden and risks
Minimum of 14 visites, duration 4 hours per visit, but for two visits patients
have to stay 10 hours in hospital, total study time is minimum 65 weeks.
Physical examination: 7 times
ECG: 14 times
Renalbiopt: 1 time (if hospital has a biopt of the patient older than 36 months)
3 Vaccines (Meningokokken, pnuemokokken en haemophilus influenza): 1 time
24 hours urine collection (at home): 4 times
Collecting first morning urine (at home): 11 times
Questionnaires: 6 times
Patient diary: Every day during treatment phase.
Taking bloodsamples:12 times
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
• Female or male adult (>=18 years) subjects at screening visit with a diagnosis
of idiopathic (primary) MN confirmed by renal biopsy within 36 months prior to
screening. A renal biopsy may be taken at any time during the run-in period to
confirm the diagnosis of MN and facilitate subject eligibility, if the most
recent biopsy was performed greater than 36 months prior to the screening visit.
• Anti-PLA2R antibody titer of >= 60 RU/mL at screening visit (based on the
EuroImmun ELISA test)
• Urine protein >= 3.5 g/24h at run-in and baseline visits
• <=50% reduction in both anti-PLA2R level and 24h urine protein between first
measurement at screening or run-in visit and baseline
• Estimated GFR (using the CKD-EPI formula) >= 30 mL/min per 1.73 m2 at
screening visit
• Receiving stable dose at the maximum recommended dose according to local
guidelines or maximum tolerated dose of ACEi and/or ARB and/or statins and/or
diuretics for at least 8 weeks prior to Day 1
• Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and
Haemophilus influenzae (in accordance with local guidelines) at least 28 days
prior to Day 1 and no longer than 5 years prior to Day 1
Exclusion criteria
• Secondary causes of MN, e.g. systemic autoimmune diseases, solid or
haematological malignancies, infections or chronic intake of drugs (e.g. gold
salts, NSAIDs, penicillamines)
• Diagnostic renal biopsy showing evidence of crescent formation in glomeruli,
suggestive of an alternative or additional diagnosis to primary idiopathic MN
• Previous treatment with B-cell depleting or B-cell modifying agents such as,
but not limited to rituximab, belimumab, daratumomab or bortezomib
• Previous treatment with immunosuppressive agents such as cyclophosphamide,
chlorambucil, mycophenolate mofetil (or equivalent), cyclosporine, tacrolimus
or azathioprine within 90 days prior to Day 1. Low dose systemic corticosteroid
therapy is permitted, though the subject should have been on stable dose
equivalent to <=10 mg prednisolone for at least 90 days prior to Day 1
• Previous treatment with gemfibrozil or strong CYP2C8 inhibitors such as
clopidogrel within 7 days prior to Day 1
• Presence or suspicion (based on judgment of the investigator) of active
infection within 30 days prior to Day 1, or history of severe recurrent
bacterial infections
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 |
|---|---|
| EudraCT | EUCTR2019-001734-34-NL |
| ClinicalTrials.gov | NCT04154787 |
| CCMO | NL70845.091.19 |