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A Proof of Concept Study for a 12 Month Treatment in Patients With C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

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ClinicalTrials.gov Identifier: NCT03459443
Recruitment Status : Recruiting
First Posted : March 9, 2018
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
Achillion Pharmaceuticals

Brief Summary:
The primary purpose of this open-label, Phase 2 proof of concept study is to evaluate the efficacy of 12 months of oral ACH-0144471 in participants with C3G or IC-MPGN based on renal biopsy results and the number and percentage of participants with an improvement relative to baseline in clinical manifestation(s) of C3G (proteinuria and reduced estimated glomerular filtration rate [eGFR]).

Condition or disease Intervention/treatment Phase
C3 Glomerulonephritis C3 Glomerulopathy Immune Complex Membranoproliferative Glomerulonephritis IC-MPGN Dense Deposit Disease Drug: ACH-0144471 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Phase 2 Proof-of-Concept Study in Patients With C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) Treated With ACH-0144471
Actual Study Start Date : June 20, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : May 2020



Intervention Details:
  • Drug: ACH-0144471
    All participants will receive ACH-0144471 oral tablets at an individually selected starting dose, with the opportunity for dose adjustment over the first two weeks.
    Other Names:
    • ACH-4471
    • ACH4471
    • 4471


Primary Outcome Measures :
  1. Change from baseline in renal biopsy, based on a score incorporating changes in both the activity index and C3 staining, at the end of 12 months of treatment [ Time Frame: Baseline, 12 months ]
  2. Percent change from baseline in renal biopsy, based on a score incorporating changes in both the activity index and C3 staining, at the end of 12 months of treatment [ Time Frame: Baseline, 12 months ]
  3. Percent of participants with significant improvement relative to baseline in clinical manifestation(s) of C3G (proteinuria, reduced eGFR, or both) at the end of 12 months of treatment [ Time Frame: Baseline, 12 months ]

Secondary Outcome Measures :
  1. Change from baseline in proteinuria over the 12 months of treatment [ Time Frame: Baseline, up to 12 months ]
  2. Percent change from baseline in proteinuria over the 12 months of treatment [ Time Frame: Baseline, 12 months ]
  3. Change from baseline in eGFR over the 12 months of treatment [ Time Frame: Baseline, 12 months ]
  4. Percent change from baseline in eGFR over the 12 months of treatment [ Time Frame: Baseline, 12 months ]
  5. Number of participants with serious adverse events (SAEs), Grade 3 and above adverse events (AEs),Grade 3 and above laboratory abnormalities, and events leading to discontinuation of study drug [ Time Frame: 16 months ]
  6. Percent of participants with serious adverse events (SAEs), Grade 3 and above adverse events (AEs),Grade 3 and above laboratory abnormalities, and events leading to discontinuation of study drug [ Time Frame: 16 months ]


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Ages Eligible for Study:   17 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. 17 to 65 years of age
  2. Completion of the ACH471-201 clinical study OR diagnosed with biopsy-confirmed primary C3G or IC-MPGN at least 3 months prior to the first dose of study drug, prior to 55 years of and not secondary to another underlying condition
  3. No more than 50% fibrosis and no more than 50% of glomeruli with cellular crescents on renal biopsy
  4. Clinical evidence of ongoing disease based on at least one of the following findings attributable to C3G disease or IC-MPGN: significant proteinuria, defined as ≥1 g/day of protein in a 24-hour urine OR an abnormal eGFR, defined as ≤75 mL/min/1.73 m2 ( CKD-EPI equation for patients > 19 years old; "Bedside Schwartz" equation for patients <19 years old).
  5. On a stable dose of anti-hypertensive medication, anti-proteinuric medications or mycophenolate mofetil (MMF) for at least 4 weeks prior to the first screening visit
  6. Female participants must use highly effective birth control to prevent pregnancy during the clinical trial and for 30 days after the last dose of study medication
  7. Male participants must use highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 90 days after the last dose of study medication
  8. Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based on local guidelines
  9. Must be willing, at all times for the duration of study participation, to have transportation and telephone access, and to be within one hour of an emergency medical center

Key Exclusion Criteria

  1. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant
  2. Have an estimated GFR <30 mL/min/1.73 m2 at the time of screening or at any time over the preceding four weeks
  3. Is receiving renal replacement therapy
  4. Have evidence of monoclonal gammopathy of unclear significance(MGUS), infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN may be secondary
  5. Have a history of febrile illness, a body temperature >38°C, or other evidence of a clinically significant active infection, within 14 days prior to ACH-0144471 administration
  6. Positive serology for human immunodeficiency virus, hepatitis B infection, or hepatitis C infection
  7. Have a history of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
  8. . Have received eculizumab at any dose or interval within the past 75 days prior to the first dose of ACH-0144471
  9. Have received tacrolimus or cyclosporine within 2 weeks of the first dose of ACH-0144471
  10. Have received blood or blood products, or undergone plasmapheresis or plasma exchange, within 30 days of screening

NOTE: Additional inclusion/exclusion criteria will apply, per protocol


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03459443


Contacts
Contact: Clinical Operations 203-752-5566 C3GTrialInquiries@achillion.com

Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
United States, California
Stanford Universtty Recruiting
Stanford, California, United States, 94305
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Australia, New South Wales
Westmead Hosptial Recruiting
Sydney, New South Wales, Australia
Australia, Queensland
Royal Brisbane and Women's Hospital Not yet recruiting
Brisbane, Queensland, Australia
Australia, Victoria
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Tom Barbour, MD         
Principal Investigator: Tom Barbour, MD         
Sponsors and Collaborators
Achillion Pharmaceuticals

Responsible Party: Achillion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03459443     History of Changes
Other Study ID Numbers: ACH471-205
First Posted: March 9, 2018    Key Record Dates
Last Update Posted: July 2, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Achillion Pharmaceuticals:
factor D
fD
alternative pathway
complement mediated disease
C3GN
DDD
idiopathic MPGN
MPGN Type I
MPGN Type II
MPGN Type III
Primary MPGN
MCGN
Mesangiocapillary Glomerulonephritis

Additional relevant MeSH terms:
Glomerulonephritis
Glomerulonephritis, Membranoproliferative
Nephritis
Kidney Diseases
Urologic Diseases
Immune System Diseases
Antigen-Antibody Complex
Immunologic Factors
Physiological Effects of Drugs