Idiopathic Membranous Nephropathy, Proteinuria
Conditions
Keywords
H.P. Acthar Gel, Acthar, nephrotic syndrome, idiopathic membranous nephropathy, proteinuria
Brief summary
The purpose of this study is to provide nephrologists with additional clinical evidence regarding the efficacy and safety of Acthar in subjects with treatment-resistant idiopathic membranous nephropathy. Approximately sixty (60) subjects will be randomized in this double-blind, parallel-group, placebo-controlled, multicenter study comparing Acthar and Placebo administered 2 times per week for a 24-week treatment period followed by a 24-week observation period. The primary objective of this study is to assess the proportion of treatment-resistant subjects (defined as subjects who either have had no response or have suffered a relapse after achieving a partial response to their most recent standard treatment regimen) who have a complete or partial remission of proteinuria in nephrotic syndrome due to idiopathic membranous nephropathy after 24 weeks of treatment.
Interventions
Acthar given SC for 6 months
DRUGPlacebo
Placebo contains the same inactive ingredients as that used for H.P. Acthar Gel without the API. Placebo given SC for 6 months (80 U two times a week).
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For complete list of inclusion and
Exclusion criteria
, please refer to contact below. Inclusion Criteria: * Male or female subjects ≥18 years of age, at screening Visit 1: a. If potential subjects are \>75 years of age, discussion between the investigator and the Medical Monitor must take place; * Body mass index ≤40 kg/m2, at screening Visit 1; * A history of nephrotic syndrome due to iMN as confirmed by documented results from a renal biopsy performed within 4 years prior to screening Visit 1: a. If a biopsy has been performed between 4-8 years prior to screening, and if the subject has no signs or symptoms of diabetes or other clinical diagnoses that could suggest a change in renal histology in the opinion of the investigator and the Medical Monitor, the subject is eligible. * Renal target disease requirements: 1. Total urine protein of ≥3.0g (≥3000mg) from the 24-hour urine returned at Visit 1A, AND. 2. An estimated glomerular filtration rate (eGFR) value \>25mL/min/1.73m2 at Visit 1A (as calculated using the abbreviated Modification of Diet in Renal Disease \[MDRD\] equation. * Any prior course of at least 1 month of treatment with ≥1 of an immunosuppressant therapy(ies) for iMN: 1. Subjects must be followed for at least 3 months after treatment prior to screening with the exception of rituximab or a cytotoxic based therapy, where the follow-up period is 6 months after treatment. If after follow-up it was determined that the subject did not achieve a complete or partial remission or suffered a relapse after achieving a partial remission, the subject will be eligible for the study. 2. If in the investigator's opinion, the subject should be enrolled prior to meeting the follow-up period criteria and the decrease in proteinuria is no longer occurring, discussion between the investigator and the Medical Monitor must take place for approval to enter screening. * History of treatment-resistant iMN defined as either having had no remission or having suffered a relapse after achieving a partial remission to their most recent standard treatment regimen as defined in the Definition of Response Status Table despite treatment with at least 1 month of treatment with a prior therapy for iMN. Note the following: a. If the subject has been treated with prior standard therapy and can no longer be re-treated with any component of that therapy, regardless of whether a complete or partial remission was achieved, then the subject may be eligible, but approval from the Medical Monitor is required. i. For example, if early discontinuation of standard therapy occurred because of a serious adverse event (Grade 3 or 4) during the treatment, regardless of whether a partial or complete remission was achieved, then the subject may be eligible. b. If (a) does not apply, and the subject did not have either a partial or complete remission to the most recent treatment regimen, then the subject is eligible. c. If (a) does not apply, and the subject achieved a partial remission from the most recent treatment regimen, and later relapse occurred, then the subject is eligible. * Antihypertensive treatment including use of ACE inhibitors and/or ARB: a. Unless there is a history of intolerance to ACE inhibitors or ARB therapy, the subject must be treated with at least one of these agents. b. Treatment with ACE inhibitor and/or ARB for ≥3 months prior to screening Visit 1A, with stable maintenance dose for ≥30 days prior to randomization. c. If treated with other antihypertensive therapies, treatment duration of ≥30 days and stable maintenance dose for ≥7 days prior to screening Visit 1A. * Blood pressure determined by the average of ≥3 seated readings taken ≥5 minutes apart during the screening period at Visit 1A: 1. Mean systolic blood pressure ≤140 mmHg and 2. Mean diastolic blood pressure ≤80 mmHg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks | At Visit 8 (Week 24) | The participant's response was considered the average of the two PCR values from the 24-hour urine collected at Visit 8 (Week 24). Urine protein creatinine ratio (uPCR) was used to assess remission (partial and complete). Complete remission = uPCR \< 0.3 g/g; partial remission = uPCR \< 50% of baseline uPCR and \> 0.3 g/g but \< 3.0 g/g. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Remission | At Visit 9 (Week 28) | The participant's response was considered the average of the two PCR values from the 24-hour urine collections at Visit 8 (Week 24). |
Countries
Canada, Chile, Mexico, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants were enrolled at study sites in United Staes. The first participant was screened on 20 October 2011. The last study visit occurred on 05 May 2017.
Pre-assignment details
132 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Acthar 40U 40 U of Acthar administered 5 times a week | 4 |
| Acthar 80U 80 U of Acthar administered 2 times a week | 35 |
| Combined Placbeo Placebo (volume matched for 40 U or 80 U) administered 5 times (40 U) or 2 times (80 U) per week | 21 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administration of live vaccines | 0 | 1 | 0 |
| Overall Study | Adverse Event | 2 | 5 | 2 |
| Overall Study | Investigator discretion | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Progressive disease | 1 | 2 | 2 |
| Overall Study | Reason not collected | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Acthar 40U | Acthar 80U | Combined Placbeo | Total |
|---|---|---|---|---|
| Age, Continuous | 55.0 Years STANDARD_DEVIATION 5.72 | 49.9 Years STANDARD_DEVIATION 13.18 | 45.4 Years STANDARD_DEVIATION 12.24 | 48.7 Years STANDARD_DEVIATION 12.65 |
| Region of Enrollment Argentina | 0 Participants | 6 Participants | 2 Participants | 8 Participants |
| Region of Enrollment Canada | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Chile | 0 Participants | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Colombia | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Mexico | 0 Participants | 4 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Turkey | 0 Participants | 6 Participants | 4 Participants | 10 Participants |
| Region of Enrollment United States | 3 Participants | 15 Participants | 10 Participants | 28 Participants |
| Sex: Female, Male Female | 2 Participants | 9 Participants | 4 Participants | 15 Participants |
| Sex: Female, Male Male | 2 Participants | 26 Participants | 17 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 35 | 0 / 21 |
| other Total, other adverse events | 4 / 4 | 31 / 35 | 18 / 21 |
| serious Total, serious adverse events | 1 / 4 | 7 / 35 | 3 / 21 |
Outcome results
Primary
Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks
The participant's response was considered the average of the two PCR values from the 24-hour urine collected at Visit 8 (Week 24). Urine protein creatinine ratio (uPCR) was used to assess remission (partial and complete). Complete remission = uPCR \< 0.3 g/g; partial remission = uPCR \< 50% of baseline uPCR and \> 0.3 g/g but \< 3.0 g/g.
Time frame: At Visit 8 (Week 24)
Population: ITT Population included all randomized participants who received ≥ 1 dose of study mediation and who contributed any efficacy data in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acthar 40U | Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks | Partial remission in proteinuria | 1 Participants |
| Acthar 40U | Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks | Complete remission in proteinuria | 0 Participants |
| Acthar 80U | Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks | Partial remission in proteinuria | 5 Participants |
| Acthar 80U | Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks | Complete remission in proteinuria | 0 Participants |
| Combined Placebo | Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks | Partial remission in proteinuria | 2 Participants |
| Combined Placebo | Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks | Complete remission in proteinuria | 0 Participants |
Secondary
Percentage of Participants With Sustained Remission
The participant's response was considered the average of the two PCR values from the 24-hour urine collections at Visit 8 (Week 24).
Time frame: At Visit 9 (Week 28)
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acthar 40U | Percentage of Participants With Sustained Remission | 1 Participants |
| Acthar 80U | Percentage of Participants With Sustained Remission | 4 Participants |
| Combined Placebo | Percentage of Participants With Sustained Remission | 2 Participants |