| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| biopsy-confirmed C3 Glomerulopathy (C3G) |
|
| E.1.1.1 | Medical condition in easily understood language |
| biopsy-confirmed C3 Glomerulopathy (C3G) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10077827 |
| E.1.2 | Term | C3 glomerulopathy |
| E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the efficacy, relative to placebo, of six months of oral ACH-0144471 in patients with C3G based on:
• Renal biopsy results
• Improvement relative to baseline in proteinuria
|
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate for improvement in eGFR following treatment with ACH-
0144471, relative to placebo, in those patients with an abnormal eGFR at
study entry
• To evaluate the safety and tolerability of ACH-0144471 in C3G patients
by assessing 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Must have confirmed primary C3G as per the following:
• Initial diagnosis of C3G established at least 3 months prior to the first dose of study drug
• Initial diagnosis prior to the age of 55
• Not secondary to another underlying condition in the opinion of the PI
2. Confirmation of DDD or C3GN diagnosis by review of a renal biopsy obtained no more than 30 days (and preferably within 2 weeks) of first dose of study drug by the study’s central pathology laboratory
3. Must be between the ages of 17 and 65 years, inclusive
4. Clinical evidence of ongoing disease based on significant proteinuria (defined as ≥1 g/day of protein in a 24-hour urine) attributable to C3G disease in the opinion of the PI, and present prior to study entry and confirmed during Screening
5. If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications (e.g., ACE inhibitors or angiotensin receptor blockers [ARBs]), or mycophenolate mofetil (MMF), must be on a stable dose for at least four weeks prior to the first screening visit
6. Female participants of childbearing potential must agree to use an acceptable method of contraception (as defined in Section 5.5.5) from the date of signing the informed consent to the first day of dosing (Day 1), and must agree to use a highly effective form of contraception (as defined in Section 5.5.5) from the first day of dosing to 30 days after their last dose of study drug. Female participants of childbearing potential must also have a negative serum pregnancy test during Screening and negative urine pregnancy test on Day 1. Female participants of non-childbearing potential need not employ a method of contraception
7. Non-sterile male participants must agree to use a highly effective form of contraception (as defined in Section 5.5.5) with their partner(s) of childbearing potential from the first day of dosing to 90 days after their last dose of study drug.
Males who are surgically sterile need not employ additional contraception.
Males must agree not to donate sperm while enrolled in this study and for 90 days after their last dose of study drug.
8. Must be capable of providing written informed consent, must be willing and able to comply with the requirements and restrictions listed in the consent form and with all procedures in the protocol, including, the visit schedule, the treatment plan, the schedule for laboratory testing, and other study procedures
9. Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based on local guidelines
10. Must be willing to comply with study-specific vaccination requirements, including those for N. meningitidis, H. influenzae, and S. pneumoniae
11. 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 |
|
| E.4 | Principal exclusion criteria |
1. Have a history or presence of any clinically relevant co-morbidities
that would make the patient inappropriate for the study (for example, a
comorbidity which is likely to result in deterioration of the patient's
condition, affect the patient's safety during the study, or confound the
results of the study), in the opinion of the PI
2. Have ever received ACH-0144471
3. Have more than 50% fibrosis or more than 50% of glomeruli with
cellular crescents on the pre-treatment renal biopsy
4. Have an estimated GFR <30 mL/min/1.73 m^2 at the time of screening or at any time over the preceding four weeks
5. Have C4 levels <80% LLN at the time of screening
6. Is a renal transplant recipient or receiving renal replacement therapy
7. Have a history of a major organ transplant (e.g., heart, lung, kidney,
liver) or hematopoietic stem cell/marrow transplant
8. Have evidence of monoclonal gammopathy of unclear
significance(MGUS), infections, malignancy, autoimmune diseases, or other conditions to which C3G may be secondary
9. Have other renal diseases that would interfere with interpretation of
the study
10. Have a comorbid condition that would pose a safety risk to the
patient, including participating in a renal biopsy, or interfere with
completion of the trial (e.g., active malignancy, uncontrolled congestive
heart failure within the previous 6 months, myocardial infarction within
the previous 12 months, other significant acute or chronic illness that is
not controlled, or requirement for continuous anticoagulant therapy)
11. Have been diagnosed with or show evidence of hepatobiliary
cholestasis
12. Are known to have Gilbert's syndrome and/or have a history
suggestive of Gilbert's syndrome
13. Females who are pregnant, nursing, or planning to become pregnant
during the study or within 90 days of study drug administration
14. 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 study drug administration
15. Have evidence of human immunodeficiency virus (HIV) (positive
serology for HIV antibody [HIV Ab]), hepatitis B infection (positive
hepatitis B surface antigen [HbsAg]), or hepatitis C infection (positive
anti-HCV antibody [HCV Ab]) at Screening or historically
16. Have a history of meningococcal infection, or a first-degree relative
or household contact with a history of meningococcal infection
17. Have a contraindication to one or more of the required vaccinations
18. 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.
19. 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 study drug
20. Have received eculizumab at any dose or interval within the past 75
days prior to the first dose of study drug
21. Have received tacrolimus or cyclosporine within 2 weeks of the first
dose of study drug
22. Have a 12-lead ECG with a QTcF >450 msec for males or >470 msec
for females, or have ECG findings which, in the opinion of the PI, could
put the patient at undue risk
23. Have received any drug known to prolong the QTc interval within 2
weeks of the first dose of study drug.
24. Have any of the following laboratory abnormalities at screening:
• Alanine transaminase (ALT) > upper limit of normal (ULN)
• Aspartate aminotransferase (AST) > ULN
• Absolute neutrophil counts (ANC) <1,000/μL
• Total bilirubin >1.5× ULN
• Indirect bilirubin > ULN
• Any laboratory abnormality that, in the opinion of the PI, would
make the patient inappropriate for the study
25. Have donated blood or blood products in excess of 500 mL within a
60 day period prior to the first dose of study drug
26. Have received blood or blood products, or undergone plasmapheresis
or plasma exchange, within 30 days of screening
27. Have a clinically significant history of drug allergy as determined by
the Investigator
28. Are unwilling or unable to comply with the study protocol for any
reason |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Change from baseline in biopsy, based on a score incorporating
changes in both the activity index and C3 staining, at the end of 6
months of treatment
• Number and percent of patients with significant improvement relative to baseline in proteinuria at the end of 6 months of treatment |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Change and percent change from baseline in proteinuria over the 6 months of treatment
• Change and percent change from baseline in eGFR over the 6 months of treatment for those patients with an abnormal eGFR at study entry
• Number and percent of patients with significant improvement relative to baseline in eGFR at the end of 6 months of treatment, for those with an abnormal eGFR at study entry |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LVLS (treatment 6 Months + 5 weeks follow-up) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
