C3 GlomerulopathyPhase 2NCT03369236
A Proof-of-Concept Study of Danicopan for 6 Months of Treatment in Participants With C3 Glomerulopathy (C3G)
A Phase 2 study testing Danicopan in people with C3 Glomerulopathy and C3 Glomerulonephritis, run by Alexion Pharmaceuticals, Inc. at 7 sites in 2 countries.
Trial summary
The primary purpose of this proof-of-concept clinical study was to evaluate the efficacy and safety of the study drug, ACH-0144471 (also known as danicopan and ALXN2040), in participants with C3G who also had significant proteinuria attributable to C3G. Read more about this study
- Who is it for?
- Ages 17 to 65 years
- Conditions the study is for
- C3 Glomerulopathy, C3 Glomerulonephritis, Dense Deposit Disease
- What is being tested?
- Danicopan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 12 Jun 2018to 18 Dec 2020
- 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 17 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Had biopsy-confirmed primary C3G
- Had clinical evidence of ongoing disease based on significant proteinuria, attributable to C3G disease in the opinion of the Principal Investigator (PI), and present prior to study entry and confirmed during Screening
- Was willing to comply with vaccination requirements.
Who cannot join
- Had a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study
- Had ever received danicopan
- Had more than 50% fibrosis or more than 50% of glomeruli with cellular crescents on the pre-treatment renal biopsy
- Had an estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared at the time of screening or at any time over the preceding 4 weeks
- Was a renal transplant recipient or receiving renal replacement therapy
- Had a history of a major organ transplant or hematopoietic stem cell/marrow transplant
Show all 13Show fewer
- Had evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G is secondary
- Had other renal diseases that would interfere with interpretation of the study
- Had been diagnosed with or showed evidence of hepatobiliary cholestasis
- Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration
- Had a 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
- Had evidence of human immunodeficiency virus, hepatitis B infection, or active hepatitis C infection at Screening
- Had laboratory abnormalities at screening that, in the opinion of the PI, would make the participant inappropriate for the study
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Clinical Study Site
Aurora, Colorado, 80045
Clinical Study Site
Baltimore, Maryland, 21205
Clinical Study Site
Iowa City, Iowa, 52242
Clinical Study Site
Lawrenceville, Georgia, 30046
Clinical Study Site
New York, New York, 10016
Clinical Study Site
New York, New York, 10032
About this study
Official title: A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, Placebo-Controlled Study of ACH-0144471 Treatment for 6 Months in Patients With C3 Glomerulopathy (C3G), With an Open-label Extension
The primary purpose of this proof-of-concept clinical study was to evaluate the efficacy and safety of the study drug, ACH-0144471 (also known as danicopan and ALXN2040), in participants with C3G who also had significant proteinuria attributable to C3G.
- Being tested
- Danicopan, Placebo
- Keywords
- factor D, fD, Alternative pathway, Complement mediated disease, Membranoproliferative Glomerulonephritis, Primary MPGN, MPGN, Mesangiocapillary Glomerulonephritis, Idiopathic MPGN, DDD, C3GN
- 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 (formerly)
Danicopan was administered as an oral tablet.
PlaceboDrug
Matching placebo was administered as an oral tablet.
| Study group | Role | What they receive |
|---|---|---|
| Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | Active comparator | Danicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period.
All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. Receives: Drug: Danicopan |
| Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | Placebo comparator | Placebo was administered TID during the 6-month treatment period.
All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. Receives: Drug: Danicopan; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline In Composite Biopsy Score At Week 28
The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of 6 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
Measured: Baseline, Week 28
Participants With Reduction In Proteinuria At Week 28
Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).
Measured: Week 28
Secondary outcomes (7)
Change From Baseline In Proteinuria At Week 28
Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.
Measured: Baseline, Week 28
Percent Change From Baseline In Proteinuria At Week 28
Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.
Measured: Baseline, Week 28
Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months
Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the 6-month blinded treatment period, with eGFR as the dependent variable and time as the independent variable.
Measured: 6 months
Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment
Slope of eGFR was estimated using a simple linear regression for each participant, including all data values during the open-label extension period with eGFR as the dependent variable and time as the independent variable.
Measured: 12 months
Change From Baseline In eGFR At Week 28
Change from baseline in eGFR at Week 28 is presented.
Measured: Baseline, Week 28
Participants With Significant Improvement In eGFR Relative To Baseline At Week 28
Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.
Measured: Baseline, Week 28
Participants With Significant Improvement In eGFR Relative To Baseline At Week 52
Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR.
Measured: Baseline, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2017
- Study start12 Jun 2018
- Primary completion11 Dec 2019
- Study completion18 Dec 2020
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 (1)Papers the sponsor has linked to this study.
- Other trials for C3 GlomerulopathyStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03369236
- Sponsor's protocol ID
- ACH471-204
- Other IDs
- 2017-000663-33, 2017
- Status last verified
- Oct 2022
- First submitted
- 17 Nov 2017
- Last updated
- 14 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Nester C, Appel GB, Bomback AS, Bouman KP, Cook HT, Daina E, Dixon BP, Rice K, Najafian N, Hui J, Podos SD, Langman CB, Lightstone L, Parikh SV, Pickering MC, Sperati CJ, Trachtman H, Tumlin J, de Vries AP, Wetzels JFM, Remuzzi G. Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies. Am J Nephrol. 2022;53(10):687-700. doi: 10.1159/000527167. Epub 2022 Nov 24.
PubMed 36423588
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, Placebo-Controlled Study of ACH-0144471 Treatment for 6 Months in Patients With C3 Glomerulopathy (C3G), With an Open-label Extension
- ClinicalTrials.gov ID
- NCT03369236
- Acronym / sponsor ID
- ACH471-204
- Keywords
- factor D, fD, Alternative pathway, Complement mediated disease, Membranoproliferative Glomerulonephritis, Primary MPGN, MPGN, Mesangiocapillary Glomerulonephritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Jun 2018 (actual)
- Primary completion
- 11 Dec 2019 (actual)
- Study completion
- 18 Dec 2020 (actual)
- First posted
- 11 Dec 2017 (actual)
- Results
- Posted 4 Nov 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 purpose of this proof-of-concept clinical study was to evaluate the efficacy and safety of the study drug, ACH-0144471 (also known as danicopan and ALXN2040), in participants with C3G who also had significant proteinuria attributable to C3G.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | Active comparator | Drug: DanicopanDanicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. |
| Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | Placebo comparator | Drug: Danicopan, Drug: PlaceboPlacebo was administered TID during the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. |
Who may qualify
- Ages
- 17 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Had biopsy-confirmed primary C3G
- Had clinical evidence of ongoing disease based on significant proteinuria, attributable to C3G disease in the opinion of the Principal Investigator (PI), and present prior to study entry and confirmed during Screening
- Was willing to comply with vaccination requirements.
Key exclusion criteria (13 listed)
- Had a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study
- Had ever received danicopan
- Had more than 50% fibrosis or more than 50% of glomeruli with cellular crescents on the pre-treatment renal biopsy
- Had an estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared at the time of screening or at any time over the preceding 4 weeks
- Was a renal transplant recipient or receiving renal replacement therapy
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-0144471 (formerly)Danicopan was administered as an oral tablet. | Drug | Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period), Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) |
| PlaceboMatching placebo was administered as an oral tablet. | Drug | Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) |
Primary outcome
Change From Baseline In Composite Biopsy Score At Week 28
Time frame: Baseline, Week 28
The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of 6 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
Participants With Reduction In Proteinuria At Week 28
Time frame: Week 28
Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).
7 secondary outcomes
Change From Baseline In Proteinuria At Week 28
Time frame: Baseline, Week 28
Percent Change From Baseline In Proteinuria At Week 28
Time frame: Baseline, Week 28
Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months
Time frame: 6 months
Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment
Time frame: 12 months
Change From Baseline In eGFR At Week 28
Time frame: Baseline, Week 28
Participants With Significant Improvement In eGFR Relative To Baseline At Week 28
Time frame: Baseline, Week 28
Participants With Significant Improvement In eGFR Relative To Baseline At Week 52
Time frame: Baseline, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36423588Nester C, Appel GB, Bomback AS, Bouman KP, Cook HT, Daina E, Dixon BP, Rice K, Najafian N, Hui J, Podos SD, Langman CB, Lightstone L, Parikh SV, Pickering MC, Sperati CJ, Trachtman H, Tumlin J, de Vries AP, Wetzels JFM, Remuzzi G. Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies. Am J Nephrol. 2022;53(10):687-700. doi: 10.1159/000527167. Epub 2022 Nov 24.
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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.
7 sites in 2 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 Glomerulopathy and C3 Glomerulonephritis, run by Alexion Pharmaceuticals, Inc. at 7 sites in 2 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 3 inclusion and 13 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 14 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, United Kingdom. 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 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 4 Nov 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 Composite Biopsy Score At Week 28 (time frame: Baseline, Week 28). 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?
On the ClinicalTrials.gov record for NCT03369236, which also lists 1 linked publication.
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 14 Oct 2022.