ProteinuriaPhase 4CHARTNCT01386554
Acthar for Treatment of Proteinuria in Membranous Nephropathy Patients
A Phase 4 study testing Repository Corticotropin Injection in people with Proteinuria and Idiopathic Membranous Nephropathy, run by Mallinckrodt at 28 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Proteinuria, Idiopathic Membranous Nephropathy
- What is being tested?
- Repository Corticotropin Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 28 sitesin 5 countries
- Study dates
- Aug 2011to 5 May 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects ≥18 years of age, at screening Visit 1:
- 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:
- 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:
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- Total urine protein of ≥3.0g (≥3000mg) from the 24-hour urine returned at Visit 1A, AND.
- 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:
- 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.
- 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:
- 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.
- 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.
- 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.
- 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:
- 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.
- 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.
- 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:
- Mean systolic blood pressure ≤140 mmHg and
- Mean diastolic blood pressure ≤80 mmHg.
Who cannot join
- Therapies and/or medications:
- History of previous use of Acthar for treatment of nephrotic syndrome;
- Prior sensitivity to Acthar or other porcine protein products; or
- Planned treatment with live or live attenuated vaccines once enrolled in the study.
- Contraindication to Acthar per Prescribing Information: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenocortical hyperfunction.
- For the purpose of this study: "history" of peptic ulcer is defined as ≤6 months prior to Visit 1A.
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- Renal target disease exclusions:
- Subjects with known diabetic nephropathy or nephrotic syndrome due to a disease or process other than idiopathic membranous nephropathy, or
- Subjects requiring diagnostic or interventional procedure requiring a contrast agent must delay screening/randomization for at least 7 days.
- History of Systemic Lupus Erythematosus.
- Type 1 or Type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus is not an exclusion).
- History of Deep Vein Thrombosis (DVT) ≤6 months prior to screening Visit 1A.
- Presence of renal vein thrombosis:
- Known current diagnosis by ultrasound, magnetic resonance imaging (MRI) or computed tomography scan;
- Signs or symptoms consistent with occurrence of acute renal vein thrombosis (hematuria in combination with flank pain and >30% unexplained acute rise in serum creatinine) with renal vein thrombosis confirmed by ultrasound, MRI or computed tomography scan.
- Cardiovascular exclusions:
- History of or active congestive heart failure (NYHA Functional Classification of CHF Class II through Class IV), or.
- History of known dilated cardiomyopathy with left ventricular ejection fraction ≤40%, or.
- Occurrence of any of the following within 3 months of screening Visit 1A:
- Unstable angina. ii. Myocardial infarction. iii. Coronary artery bypass graft or percutaneous transluminal coronary angioplasty.
- Transient ischemic attack or cerebrovascular disease. v. unstable arrhythmia.
Trial locations and contacts
28 sites in 5 countries.
28 sites in 5 countries
United States14 sites
Mallinckrodt Investigational Site
Atlanta, Georgia, 30322
Mallinckrodt Investigational Site
Bethlehem, Pennsylvania, 18017
Mallinckrodt Investigational Site
Chapel Hill, North Carolina, 27599
Mallinckrodt Investigational Site
Charleston, South Carolina, 29425
Mallinckrodt Investigational Site
Chattanooga, Tennessee, 37404
Mallinckrodt Investigational Site
Durham, North Carolina, 27705
Mallinckrodt Investigational Site
Houston, Texas, 77030
Mallinckrodt Investigational Site
Jacksonville, Florida, 32209
Mallinckrodt Investigational Site
Lubbock, Texas, 79430
Mallinckrodt Investigational Site
New York, New York, 10032
Mallinckrodt Investigational Site
Reno, Nevada, 89502
Mallinckrodt Investigational Site
Rochester, Minnesota, 55905
Mallinckrodt Investigational Site
Sacramento, California, 95825
Mallinckrodt Investigational Site
Stanford, California, 94304
Turkey (Türkiye)9 sites
Mallinckrodt Investigational Site 307
Adana
Mallinckrodt Investigational Site 305
Ankara
Mallinckrodt Investigational Site 308
Ankara
Mallinckrodt Investigational Site 302
Antalya
Mallinckrodt Investigational Site 301
Istanbul
Mallinckrodt Investigational Site 309
Istanbul
Mallinckrodt Investigational Site 303
Izmir
Mallinckrodt Investigational Site 310
Kocaeli
Mallinckrodt Investigational Site 304
Mersin
Chile2 sites
Mallinckrodt Investigational Site
La Serena, Coquimbo Region
Mallinckrodt Investigational Site
Temuco
Mexico2 sites
Mallinckrodt Investigational Site
Monterrey, Nuevo León
Mallinckrodt Investigational Site
San Nicolás de los Garza, Nuevo León
About this study
Official title: A Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Study of H.P. Acthar Gel (Acthar) in Treatment-Resistant Subjects With Persistent Proteinuria and Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy (iMN)
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.
- Conditions
- Proteinuria, Idiopathic Membranous Nephropathy
- Being tested
- Repository Corticotropin Injection, Placebo
- Keywords
- H.P. Acthar Gel, Acthar, nephrotic syndrome, idiopathic membranous nephropathy, proteinuria
- Medical subject headings
- Proteinuria, Glomerulonephritis, Membranous, Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repository Corticotropin InjectionDrug
Also called H.P. Acthar Gel, ACTH Gel, ACTH
Acthar given SC for 6 months
PlaceboDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 80 U Acthar | Experimental | Acthar (Repository Corticotropin Injection) 80 U (1.0 mL) two times per week Receives: Drug: Repository Corticotropin Injection |
| 1.0 mL Placebo | Placebo comparator | Placebo (1.0 mL) two times per week Receives: Drug: Placebo |
| 40 U Acthar | Experimental | Acthar (Repository Corticotropin Injection) 40 U (1.0 mL) two times per week Receives: Drug: Repository Corticotropin Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At Visit 8 (Week 24)
Secondary outcomes (1)
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).
Measured: At Visit 9 (Week 28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2011 (estimated)
- Study startAug 2011
- Primary completion21 Nov 2016
- Study completion5 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ProteinuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mallinckrodt
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Mallinckrodt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01386554
- Sponsor's protocol ID
- QSC01-MN-01
- Other IDs
- Control No. 166679
- Acronym
- CHART
- Status last verified
- Apr 2018
- First submitted
- 29 Jun 2011
- Last updated
- 20 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Publications
Bomback AS, Tumlin JA, Baranski J, Bourdeau JE, Besarab A, Appel AS, Radhakrishnan J, Appel GB. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011 Mar 14;5:147-53. doi: 10.2147/DDDT.S17521.
PubMed 21448451von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.
PubMed 34778952
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Study of H.P. Acthar Gel (Acthar) in Treatment-Resistant Subjects With Persistent Proteinuria and Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy (iMN)
- ClinicalTrials.gov ID
- NCT01386554
- Acronym / sponsor ID
- CHART / QSC01-MN-01
- Conditions
- Proteinuria, Idiopathic Membranous Nephropathy
- Keywords
- H.P. Acthar Gel, Acthar, nephrotic syndrome, idiopathic membranous nephropathy, proteinuria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- MallinckrodtIndustry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- 21 Nov 2016 (actual)
- Study completion
- 5 May 2017 (actual)
- First posted
- 1 Jul 2011 (estimated)
- Results
- Posted 26 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 80 U Acthar | Experimental | Drug: Repository Corticotropin InjectionActhar (Repository Corticotropin Injection) 80 U (1.0 mL) two times per week |
| 1.0 mL Placebo | Placebo comparator | Drug: PlaceboPlacebo (1.0 mL) two times per week |
| 40 U Acthar | Experimental | Drug: Repository Corticotropin InjectionActhar (Repository Corticotropin Injection) 40 U (1.0 mL) two times per week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Male or female subjects ≥18 years of age, at screening Visit 1:
- 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:
- Renal target disease requirements:
- Any prior course of at least 1 month of treatment with ≥1 of an immunosuppressant therapy(ies) for iMN:
Key exclusion criteria (21 listed)
- Therapies and/or medications:
- Contraindication to Acthar per Prescribing Information: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenocortical hyperfunction.
- Renal target disease exclusions:
- History of Systemic Lupus Erythematosus.
- Type 1 or Type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus is not an exclusion).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repository Corticotropin InjectionAlso: H.P. Acthar Gel, ACTH Gel, ACTHActhar given SC for 6 months | Drug | 40 U Acthar, 80 U Acthar |
| PlaceboPlacebo 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). | Drug | 1.0 mL Placebo |
Primary outcome
Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks
Time frame: 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.
1 secondary outcome
Percentage of Participants With Sustained Remission
Time frame: At Visit 9 (Week 28)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21448451Bomback AS, Tumlin JA, Baranski J, Bourdeau JE, Besarab A, Appel AS, Radhakrishnan J, Appel GB. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011 Mar 14;5:147-53. doi: 10.2147/DDDT.S17521.
- Derived from this study: PubMed 34778952von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Mallinckrodt
28 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Repository Corticotropin Injection in people with Proteinuria and Idiopathic Membranous Nephropathy, run by Mallinckrodt at 28 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Turkey (Türkiye), Chile, Mexico, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks (time frame: At Visit 8 (Week 24)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01386554, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2019.