A Proof of Concept Study for a 12 Month Treatment in Patients With C3G or IC-MPGN Treated With ACH-0144471

• Register: ClinicalTrials.gov
• Last refreshed on: 28 August 2023
• Main ID: NCT03459443
• Date of registration: 26/02/2018
• Prospective Registration: Yes
• Primary sponsor: Alexion
• Public title: A Proof of Concept Study for a 12 Month Treatment in Patients With C3G or IC-MPGN Treated With ACH-0144471
• Scientific 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
• Date of first enrolment: June 20, 2018
• Target sample size: 22
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03459443
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Australia, Belgium, Italy, Netherlands, United States

Key inclusion & exclusion criteria

Key Inclusion Criteria:

1. At least 12 years of age

2. Completion of the ACH471-201 clinical study OR diagnosed with biopsy-confirmed primary
C3G or IC-MPGN

3. If a pre-treatment biopsy is obtained, or if a historical biopsy is available for
review, it must have no more than 50% global fibrosis and no more than 50% of
glomeruli with cellular crescents

4. Clinical evidence of ongoing disease based on significant proteinuria (defined as =500
mg/day of protein in a 24-hour urine) attributable to C3G disease or IC-MPGN in the
opinion of the principal investigator (PI), and present prior to study entry and
confirmed during Screening

5. If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications
(for example, angiotensin-converting enzyme inhibitors or angiotensin receptor
blockers), or mycophenolate mofetil, must be on a stable dose for at least 2 weeks
prior to screening

6. Female participants must use an acceptable method birth control to prevent pregnancy
during the clinical study 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 study 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 have access to emergency medical care

Key Exclusion Criteria

1. Have a history of a major organ transplant (for example, heart, lung, kidney, or
liver) or hematopoietic stem cell/marrow transplant

2. Have a history or presence of any clinically relevant co-morbidities that would make
the participant inappropriate for the study (for example, a comorbidity that is likely
to result in deterioration of the participant's condition, affect the participant's
safety during the study, or confound the results of the study), in the opinion of the
PI

3. Have an eGFR <30 milliliter/minute/1.73 m^2 at the time of screening or at any time
over the preceding 4 weeks

4. Is a renal transplant recipient or receiving renal replacement therapy

5. Have other renal diseases that would interfere with the interpretation of the study

6. Have evidence of monoclonal gammopathy of unclear significance, infections,
malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN is
secondary

7. Have been diagnosed with or show evidence of hepatobiliary cholestasis

8. Females who are pregnant, nursing, or planning to become pregnant during the study or
within 90 days of ACH-0144471 administration or participants with a female partner who
is pregnant, nursing, or planning to become pregnant during the study or within 90
days of ACH-0144471 administration

9. Have a history of febrile illness, a body temperature >38°Celsius, or other evidence
of a clinically significant active infection, within 14 days prior to danicopan
administration

10. Have evidence of human immunodeficiency virus, hepatitis B infection, or active
hepatitis C infection at Screening

11. Have a history of meningococcal infection within the prior year

12. Have a history of hypersensitivity reactions to commonly used antibacterial agents,
including beta-lactams, penicillin, aminopenicillins, fluoroquinolones,
cephalosporins, and carbapenems, which, in the opinion of the investigator and/or an
appropriately qualified immunology or infectious disease expert, would make it
difficult to properly provide either empiric antibiotic therapy or treat an active
infection.

13. Have participated in a clinical study in which an investigational drug was given
within 30 days, or within 5 half-lives of the investigational drug, whichever is
longer, prior to the first dose of ACH-0144471

14. Have received eculizumab at any dose or interval within the past 50 days prior to the
first dose of ACH-0144471

15. Have received tacrolimus or cyclosporine within 2 weeks of the first dose of
ACH-0144471

16. Have a 12-lead electrocardiogram (ECG) with a QT interval Fridericia correction
formula >450 millisecond (msec) for males or >470 msec for females, or have ECG
findings which, in the opinion of the PI, could put the participant at undue risk

17. Have received any drug known to prolong the corrected QT interval within 2 weeks of
the first dose of ACH-0144471 and which, in the opinion of the PI, could put the
participant at undue risk

18. Have any of the following laboratory abnormalities at screening:

- Alanine transaminase > upper limit of normal (ULN)

- Aspartate aminotransferase > ULN

- Absolute neutrophil counts <1,000/microliter

- Total bilirubin >1.5* ULN

- Indirect bilirubin > ULN

- Any laboratory abnormality that, in the opinion of the PI, would make the
participant inappropriate for the study

19. Unwilling or unable to comply with the study protocol for any reason



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

C3 Glomerulopathy

Immune Complex Membranoproliferative Glomerulonephritis

IC-MPGN

C3 Glomerulonephritis

Dense Deposit Disease

Intervention(s)

Drug: Danicopan

Primary Outcome(s)

Participants With Reduction In Proteinuria At End Of Initial 12-Month Treatment Period [Time Frame: Baseline, end of initial 12-Month Treatment Period]

Change From Baseline In Composite Biopsy Score At End Of Initial 12-Month Treatment Period [Time Frame: Baseline, end of initial 12-Month Treatment Period]

Secondary Outcome(s)

Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period [Time Frame: Baseline, end of initial 12-Month Treatment Period]

Change From Baseline In Measured GFR At The End Of The Initial 12-Month Treatment Period [Time Frame: End of initial 12-Month Treatment Period]

Percent Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period [Time Frame: Baseline, end of initial 12-Month Treatment Period]

Participants With Significant Improvement In eGFR Relative To Baseline At End Of Initial 12-Month Treatment Period [Time Frame: Baseline, end of initial 12-Month Treatment Period]

Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period [Time Frame: Baseline, end of initial 12-Month Treatment Period]

Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To End Of Initial 12-Month Treatment Period [Time Frame: End of initial 12-Month Treatment Period]

Change From Baseline in eGFR Over 12 Months of Treatment For Participants Meeting eGFR Inclusion Criteria [Time Frame: End of initial 12-Month Treatment Period]

Secondary ID(s)

ACH471-205

2017-002674-39

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/08/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03459443