C3 GlomerulonephritisPhase 2NCT03124368
A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN
A Phase 2 study testing Danicopan in people with C3 Glomerulonephritis and Dense Deposit Disease, run by Alexion Pharmaceuticals, Inc. at 3 sites in 3 countries.
Trial summary
The primary objective of this study was to determine whether ACH-0144471 (also known as danicopan and ALXN2040) increases blood C3 complement protein (C3) levels in participants with low C3 levels due to either C3G or IC-MPGN. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- C3 Glomerulonephritis, Dense Deposit Disease, C3 Glomerulopathy
- What is being tested?
- Danicopan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 9 Aug 2017to 9 Jan 2019
- Phase
- Phase 2
- 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 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Must have had clinical diagnosis of C3G (C3 glomerulonephritis or dense deposit disease, the 2 types of C3G) or idiopathic IC-MPGN by renal biopsy for at least 3 months prior to dosing, with the pathologic diagnosis verified by a review of the renal biopsy by the study central pathologist
- C3 must have been <50% of the lower limit of normal
- C4 complement protein (C4) must have been >90% of the lower limit of normal
- Must have been willing to comply with study-specific vaccination requirements for Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis strains A, C, W, and Y
- Negative pregnancy test for females prior to dosing and throughout the study
Who cannot join
- History of a major organ transplant (for example, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. Individuals receiving renal replacement therapy were also excluded
- Evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN may have been secondary
- Estimated glomerular filtration rate (using Modification of Diet in Renal Disease equation) <45 milliliters/minute/1.73 square meters at the time of Screening or at any time over the preceding 4 weeks
- Receipt of eculizumab at any dose or interval within the past 75 days prior to dosing
- Use of tacrolimus or cyclosporine within 2 weeks of the first dose of danicopan
- History of febrile illness, a body temperature >38°Celsius, or other evidence of a clinically significant active infection, within 14 days prior to study drug administration
- History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
- Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration or participants with a female partner who was pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: A Phase 2a Proof-of-Mechanism, Open-Label Study to Determine the Effect of ACH-0144471 on C3 Levels in Participants With Low C3 Levels Due to Either C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
The primary objective of this study was to determine whether ACH-0144471 (also known as danicopan and ALXN2040) increases blood C3 complement protein (C3) levels in participants with low C3 levels due to either C3G or IC-MPGN.
- Conditions
- C3 Glomerulonephritis, Dense Deposit Disease, C3 Glomerulopathy, Immune Complex Mediated Membranoproliferative Glomerulonephritis, Membranoproliferative Glomerulonephritis Types I, II, and III
- Being tested
- Danicopan
- Keywords
- factor D, FD, alternative pathway, complement mediated disease, idiopathic MPGN, MPGN Type I, MPGN Type II, MPGN Type III, Primary MPGN, MCGN, Mesangiocapillary Glomerulonephritis, C3 Glomerulopathy, C3G, Membranoproliferative Glomerulonephritis, C3GN, Dense Deposit Disease, DDD
- Medical subject headings
- Glomerulonephritis, Membranoproliferative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DanicopanDrug
Also called ACH-4471, ACH4471, 4471, ACH-0144471
Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period).
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Experimental | All participants received 100 milligrams (mg) of danicopan three times per day (TID) during the Treatment Period. Receives: Drug: Danicopan |
| Group 2: Danicopan up to 200 mg TID | Experimental | All participants received not more than 200 mg of danicopan TID depending on the available safety, pharmacokinetic, and pharmacodynamic data from Group 1 (Sentinel) during the Treatment Period. Receives: Drug: Danicopan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method.
Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels
Measured: Baseline, Day 15
Change From Baseline In Plasma Intact C3 Level On Day 15
Plasma Intact C3 level were measured by a novel multiplex assay method. Change from Baseline = Plasma Intact C3 levels on Day 15 - Baseline Plasma Intact C3 levels
Measured: Baseline, Day 15
Secondary outcomes (9)
Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14
CP activity was measured in serum by the DiaSorin Complement Activation Enzyme (CAE) functional immunoassay method, which measures terminal complement complex formation following activation. Results are expressed in CAE units which are calculated relative to previously established CAE activity of a positive control serum.
Change from Baseline = Total Complement CP Activity on Day 14 - Baseline Total Complement CP Activity
Measured: Baseline, Day 14
Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15
AP functional activity was measured in serum by the Wieslab functional immunoassay method, which measures terminal complement complex (TCC) formation following AP-specific activation. Results are expressed as percent TCC production relative to a positive control serum.
Change from Baseline = Total Complement AP Functional Activity on Day 15 - Baseline Total Complement AP Functional Activity
Measured: Baseline, Day 15
Time To Achieving Peak Serum C3 Levels
Serial serum samples were collected on Days 1, 7, and 14.
Measured: From The First Day Of Dosing through Day 14
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The intensity of an AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Adverse Event Severity Grading Table. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Measured: Up to Day 49
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8)
Serial blood samples were collected at 0, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose on Days 1 and 7.
Measured: Days 1 and 7
PK: Maximum Plasma Concentration (Cmax)
Serial blood samples were collected at 0, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose on Days 1 and 7.
Measured: Days 1 and 7
PK: Time To Maximum Concentration (Tmax)
Serial blood samples were collected at 0, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose on Days 1 and 7.
Measured: Days 1 and 7
Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15
Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA).
Change from Baseline = Complement Bb on Day 15 - Baseline
Measured: Baseline, Day 15
Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15
Plasma sC5b-9 was measured by ELISA.
Change from Baseline = sC5b-9 on Day 15 - Baseline sC5b-9
Measured: Baseline, Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2017
- Study start9 Aug 2017
- Primary completion21 Dec 2018
- Study completion9 Jan 2019
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.
- Other trials for C3 GlomerulonephritisStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Achillion, a wholly owned subsidiary of Alexion
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03124368
- Sponsor's protocol ID
- ACH471-201
- Other IDs
- 2016-003525-42, 2016
- Status last verified
- Oct 2021
- First submitted
- 12 Apr 2017
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Proof-of-Mechanism, Open-Label Study to Determine the Effect of ACH-0144471 on C3 Levels in Participants With Low C3 Levels Due to Either C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
- ClinicalTrials.gov ID
- NCT03124368
- Acronym / sponsor ID
- ACH471-201
- Conditions
- C3 Glomerulonephritis, Dense Deposit Disease, C3 Glomerulopathy, Immune Complex Mediated Membranoproliferative Glomerulonephritis, Membranoproliferative Glomerulonephritis Types I, II, and III
- Keywords
- factor D, FD, alternative pathway, complement mediated disease, idiopathic MPGN, MPGN Type I, MPGN Type II, MPGN Type III
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Achillion, a wholly owned subsidiary of Alexion
- Study start
- 9 Aug 2017 (actual)
- Primary completion
- 21 Dec 2018 (actual)
- Study completion
- 9 Jan 2019 (actual)
- First posted
- 21 Apr 2017 (actual)
- Results
- Posted 13 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study was to determine whether ACH-0144471 (also known as danicopan and ALXN2040) increases blood C3 complement protein (C3) levels in participants with low C3 levels due to either C3G or IC-MPGN.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Danicopan 100 mg TID (Sentinel) | Experimental | Drug: DanicopanAll participants received 100 milligrams (mg) of danicopan three times per day (TID) during the Treatment Period. |
| Group 2: Danicopan up to 200 mg TID | Experimental | Drug: DanicopanAll participants received not more than 200 mg of danicopan TID depending on the available safety, pharmacokinetic, and pharmacodynamic data from Group 1 (Sentinel) during the Treatment Period. |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Must have had clinical diagnosis of C3G (C3 glomerulonephritis or dense deposit disease, the 2 types of C3G) or idiopathic IC-MPGN by renal biopsy for at least 3 months prior to dosing, with the pathologic diagnosis verified by a review of the renal biopsy by the study central pathologist
- C3 must have been <50% of the lower limit of normal
- C4 complement protein (C4) must have been >90% of the lower limit of normal
- Must have been willing to comply with study-specific vaccination requirements for Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis strains A, C, W, and Y
- Negative pregnancy test for females prior to dosing and throughout the study
Key exclusion criteria (8 listed)
- History of a major organ transplant (for example, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. Individuals receiving renal replacement therapy were also excluded
- Evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN may have been secondary
- Estimated glomerular filtration rate (using Modification of Diet in Renal Disease equation) <45 milliliters/minute/1.73 square meters at the time of Screening or at any time over the preceding 4 weeks
- Receipt of eculizumab at any dose or interval within the past 75 days prior to dosing
- Use of tacrolimus or cyclosporine within 2 weeks of the first dose of danicopan
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 |
|---|---|---|
| DanicopanAlso: ACH-4471, ACH4471, 4471, ACH-0144471Participants received study drug for 14 days (Treatment Period), followed by a taper over the next 7 days (Taper Period). | Drug | Group 1: Danicopan 100 mg TID (Sentinel), Group 2: Danicopan up to 200 mg TID |
Primary outcome
Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
Time frame: Baseline, Day 15
Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels
Change From Baseline In Plasma Intact C3 Level On Day 15
Time frame: Baseline, Day 15
Plasma Intact C3 level were measured by a novel multiplex assay method. Change from Baseline = Plasma Intact C3 levels on Day 15 - Baseline Plasma Intact C3 levels
9 secondary outcomes
Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14
Time frame: Baseline, Day 14
Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15
Time frame: Baseline, Day 15
Time To Achieving Peak Serum C3 Levels
Time frame: From The First Day Of Dosing through Day 14
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
Time frame: Up to Day 49
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8)
Time frame: Days 1 and 7
PK: Maximum Plasma Concentration (Cmax)
Time frame: Days 1 and 7
PK: Time To Maximum Concentration (Tmax)
Time frame: Days 1 and 7
Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15
Time frame: Baseline, Day 15
Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15
Time frame: Baseline, Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Not yet recruitingObservational study
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Glomerulopathy, C3G
Not yet recruitingPhase 3
To Assess the Efficacy and Safety of Pegcetacoplan for the Prevention of Recurrent C3G or Primary IC-MPGN in Kidney Transplant Recipients
C3 Glomerulopathy (C3G), Primary Immune-Complex Membranoproliferative
RecruitingPhase 2
A Phase 2 Study to Evaluate the Safety, PD, PK, and Clinical Activity of ADX-097 in Participants With IgAN, LN or C3G
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RecruitingPhase 4
Real-World Effectiveness and Safety of Pegcetacoplan in Patients With C3G or IC-MPG: A Multi-Country Study
C3 Glomerulopathy (C3G), Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
Active, not recruitingPhase 2
A Study of SGB-9768 in Patients With Complement-mediated Kidney Diseases
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Danicopan in people with C3 Glomerulonephritis and Dense Deposit Disease, run by Alexion Pharmaceuticals, Inc. at 3 sites in 3 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 5 inclusion and 8 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 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia, Belgium, Netherlands. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 13 Jul 2021). 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?
Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15 (time frame: Baseline, Day 15). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Nov 2021.