Atypical Hemolytic Uremic SyndromePhase 3APPELHUSNCT04889430
Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
A Phase 3 study testing Iptacopan in people with Atypical Hemolytic Uremic Syndrome, run by Novartis Pharmaceuticals at 36 sites in 8 countries.
Trial summary
The purpose of this Phase 3 study is to determine whether iptacopan (LNP023) is efficacious and safe for the treatment of aHUS in adult patients who are treatment naive to complement inhibitor therapy. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Atypical Hemolytic Uremic Syndrome
- What is being tested?
- Iptacopan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 36 sitesin 8 countries
- Study dates
- 17 Jan 2022to 11 Apr 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria:
- Adult patients with evidence of active thrombotic microangiopathy (TMA), including thrombocytopenia, evidence of hemolysis, and acute kidney injury
- Vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections are required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations, at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination or before vaccination is given, prophylactic antibiotic treatment must be administered at the start of study treatment and for at least 2 weeks after vaccination
Main Exclusion Criteria:
- Treatment with complement inhibitors, including anti-C5 antibody
- ADAMTS13 deficiency (<10% activity or <0.1U/ml), and/or Shiga toxin-related hemolytic uremic syndrome (STx-HUS), and/or Positive direct Coombs test
- Identified drug exposure-related HUS or HUS related to known genetic defects of cobalamin C metabolism or known diacylglycerol kinase ε (DGKE) mediated aHUS
- Receiving PE/PI, for 14 days or longer, prior to the start of screening for the current TMA
- Bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT), heart, lung, small bowel, pancreas, or liver transplantation
- Patients with sepsis or active severe systemic bacterial, viral (including COVID-19) or fungal infection, systemic infection which confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease, active infection (or history of recurrent invasive infections) caused by encapsulated bacteria
- Kidney disease suggestive of other disease than aHUS or of chronic kidney failure or family history of non-complement mediated genetic kidney disease
- Liver disease or liver injury at screening
- Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome
- Chronic hemo- or peritoneal dialysis
Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
36 sites in 8 countries.
36 sites in 8 countries
United States16 sites
University of Cincinnati
Cincinnati, Ohio, 45267-0585
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Comprehensive Transplant Ctr at OSU
Columbus, Ohio, 43210
UT Southwestern Medical Center
Dallas, Texas, 75390
Duke University Medical Center
Durham, North Carolina, 27710
USC Norris Cancer Center
Los Angeles, California, 90033
Univ of California at Los Angeles
Los Angeles, California, 90095
University Of Miami
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Univ Cali Irvine ALS Neuromuscular
Orange, California, 92868
Virginia Commonwealth University
Richmond, Virginia, 23298
Univ of California at Sacramento
Sacramento, California, 95817
Montefiore Medical Center .
The Bronx, New York, 10461
Montefiore Medical Center
The Bronx, New York, 10461
Harbor-UCLA Medical Center .
Torrance, California, 90502
Georgetown University Lombardi Cancer Center
Washington D.C., District of Columbia, 20007-2197
Brazil10 sites
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30150-221
Novartis Investigative Site
Brasília, Federal District, 71635-580
Novartis Investigative Site
Fortaleza, Ceará, 60430 370
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90035-074
Novartis Investigative Site
Recife, Pernambuco, 50740-900
Novartis Investigative Site
Rio de Janeiro, 22270-060
Novartis Investigative Site
Salvador, 40323-010
Novartis Investigative Site
São Paulo, São Paulo, 01327 001
Novartis Investigative Site
São Paulo, São Paulo, 04038-002
Novartis Investigative Site
São Paulo, São Paulo, 05403 000
India4 sites
Novartis Investigative Site
Chandigarh, Punjab, 160012
Novartis Investigative Site
Lucknow, Uttar Pradesh, 226014
Novartis Investigative Site
Nagpur, Maharashtra, 440015
Novartis Investigative Site
Pune, Maharashtra, 411011
Taiwan2 sites
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taoyuan, 33305
About this study
Official title: A Multicenter, Single-arm, Open Label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily LNP023 in Adult aHUS Patients Who Are Naive to Complement Inhibitor Therapy
The purpose of this Phase 3 study is to determine whether iptacopan (LNP023) is efficacious and safe for the treatment of aHUS in adult patients who are treatment naive to complement inhibitor therapy.
Read the detailed description
The study is designed as a multicenter, single-arm, open label study to demonstrate the efficacy and safety of LNP023 (iptacopan) at a dose of 200 mg b.i.d. in adult patients with aHUS who are treatment naive to complement inhibitor therapy (including anti-C5 antibody). The study will enroll approximately 50 participants and assess the effects of iptacopan on a range of efficacy assessments relevant to aHUS including hematological and kidney parameters, dialysis requirement, changes in chronic kidney disease (CKD) stage, as well as patient reported outcomes (PRO) for fatigue and quality of life.
- Conditions
- Atypical Hemolytic Uremic Syndrome
- Being tested
- Iptacopan
- Keywords
- LNP023, iptacopan, aHUS, atypical hemolytic uremic syndrome, thrombotic microangiopathy
- Medical subject headings
- Atypical Hemolytic Uremic Syndrome, Thrombotic Microangiopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IptacopanDrug
Also called LNP023
Iptacopan 200mg twice daily oral
| Study group | Role | What they receive |
|---|---|---|
| Iptacopan 200 mg b.i.d | Experimental | Single arm open-label with 50 adult patients receiving 200mg oral twice daily doses of iptacopan Receives: Drug: Iptacopan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody
The number/percentage of participants treated with iptacopan achieving complete thrombotic microangiopathy (TMA) response during 26 weeks of study treatment.
Complete TMA Response is defined as (1) hematological normalization in platelet count (platelet count ≥150 x 10^9/L) and LDH (below ULN), and (2) improvement in kidney function (≥ 25% serum creatinine reduction from baseline), maintained for two measurements obtained at least four weeks apart, and any measurement in between
Measured: 26 weeks of study treatment
Long term safety and efficacy evaluations
Long term (one year) safety, tolerability and efficacy of iptacopan via 1) safety evaluations including adverse events/serious adverse events, safety laboratory parameters, vital signs etc. after 52 weeks of study treatment, and 2) efficacy evaluations including complete TMA response, hematological parameters (platelets, LDH, hemoglobin), eGFR, PROs after 52 weeks of study treatment
Measured: 52 weeks of study treatment
Secondary outcomes (10)
Time to achieve complete TMA response
Effect of study treatment iptacopan on time to complete TMA response during the first 26 weeks of study treatment
Measured: 26 weeks of study treatment
Percentage of participants with increase from baseline in hemoglobin levels ≥ 2 g/dL
Response is defined as the percentage of participants with an increase in hemoglobin of ≥ 2 g/dL from baseline, observed at two measurements obtained at least 4 weeks apart and any measurement in between during 26 weeks of study treatment
Measured: 26 weeks of study treatment
Change from baseline on hematologic parameters
Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at Week 26
Measured: At week 26
Percentage of participants on dialysis
For participants requiring dialysis within 5 days prior to iptacopan treatment initiation, the number of participants who no longer require dialysis through 26 weeks of study treatment will be evaluated by means of proportion and corresponding confidence interval
Measured: 26 weeks of study treatment
Change from baseline on estimated glomerular filtration rate
Change from baseline in eGFR after 26 weeks of study treatment.
Measured: At week 26
Change from baseline in chronic kidney disease (CKD) stage
Change from baseline in CKD stage (1-5) based on eGFR categories at Week 26
Measured: At week 26
Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire
Change from baseline in patient-reported outcomes scores for FACIT-Fatigue Questionnaire at Week 26
Measured: At week 26
Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire
Change from baseline in patient-reported outcomes scores for the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire at Week 26
Measured: At Week 26
Change from baseline in patient-reported outcomes score as measured by the Patient Global Impression of Severity (PGIS) questionnaire
Change from baseline in patient-reported outcomes scores for Patient Global Impression of Severity (PGIS) at Week 26
Measured: At Week 26
Change from baseline in patient-reported outcomes score as measured by the Short-form 36 health survey questionnaire version 2 (SF-36 v2)
Change from baseline in patient-reported outcomes scores for Short-form 36 health survey questionnaire version 2 (SF-36 v2) at Week 26
Measured: At Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2021
- Study start17 Jan 2022
- Primary completion11 Apr 2026
- Study completion11 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atypical Hemolytic Uremic SyndromeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04889430
- Sponsor's protocol ID
- CLNP023F12301
- Other IDs
- 2020-005186-13
- Acronym
- APPELHUS
- Status last verified
- Aug 2026
- First submitted
- 7 May 2021
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient level data and supporting clinical documents from eligible studies. these requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Single-arm, Open Label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily LNP023 in Adult aHUS Patients Who Are Naive to Complement Inhibitor Therapy
- ClinicalTrials.gov ID
- NCT04889430
- Acronym / sponsor ID
- APPELHUS / CLNP023F12301
- Conditions
- Atypical Hemolytic Uremic Syndrome
- Keywords
- LNP023, iptacopan, aHUS, atypical hemolytic uremic syndrome, thrombotic microangiopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 Jan 2022 (actual)
- Primary completion
- 11 Apr 2026 (actual)
- Study completion
- 11 Apr 2026 (actual)
- First posted
- 17 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase 3 study is to determine whether iptacopan (LNP023) is efficacious and safe for the treatment of aHUS in adult patients who are treatment naive to complement inhibitor therapy.
Detailed description
The study is designed as a multicenter, single-arm, open label study to demonstrate the efficacy and safety of LNP023 (iptacopan) at a dose of 200 mg b.i.d. in adult patients with aHUS who are treatment naive to complement inhibitor therapy (including anti-C5 antibody). The study will enroll approximately 50 participants and assess the effects of iptacopan on a range of efficacy assessments relevant to aHUS including hematological and kidney parameters, dialysis requirement, changes in chronic kidney disease (CKD) stage, as well as patient reported outcomes (PRO) for fatigue and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Iptacopan 200 mg b.i.d | Experimental | Drug: IptacopanSingle arm open-label with 50 adult patients receiving 200mg oral twice daily doses of iptacopan |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| IptacopanAlso: LNP023Iptacopan 200mg twice daily oral | Drug | Iptacopan 200 mg b.i.d |
Primary outcome
Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody
Time frame: 26 weeks of study treatment
The number/percentage of participants treated with iptacopan achieving complete thrombotic microangiopathy (TMA) response during 26 weeks of study treatment. Complete TMA Response is defined as (1) hematological normalization in platelet count (platelet count ≥150 x 10^9/L) and LDH (below ULN), and (2) improvement in kidney function (≥ 25% serum creatinine reduction from baseline), maintained for two measurements obtained at least four weeks apart, and any measurement in between
Long term safety and efficacy evaluations
Time frame: 52 weeks of study treatment
Long term (one year) safety, tolerability and efficacy of iptacopan via 1) safety evaluations including adverse events/serious adverse events, safety laboratory parameters, vital signs etc. after 52 weeks of study treatment, and 2) efficacy evaluations including complete TMA response, hematological parameters (platelets, LDH, hemoglobin), eGFR, PROs after 52 weeks of study treatment
10 secondary outcomes
Time to achieve complete TMA response
Time frame: 26 weeks of study treatment
Percentage of participants with increase from baseline in hemoglobin levels ≥ 2 g/dL
Time frame: 26 weeks of study treatment
Change from baseline on hematologic parameters
Time frame: At week 26
Percentage of participants on dialysis
Time frame: 26 weeks of study treatment
Change from baseline on estimated glomerular filtration rate
Time frame: At week 26
Change from baseline in chronic kidney disease (CKD) stage
Time frame: At week 26
Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire
Time frame: At week 26
Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire
Time frame: At Week 26
Change from baseline in patient-reported outcomes score as measured by the Patient Global Impression of Severity (PGIS) questionnaire
Time frame: At Week 26
Change from baseline in patient-reported outcomes score as measured by the Short-form 36 health survey questionnaire version 2 (SF-36 v2)
Time frame: At Week 26
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient level data and supporting clinical documents from eligible studies. these requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
36 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Iptacopan in people with Atypical Hemolytic Uremic Syndrome, run by Novartis Pharmaceuticals at 36 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Brazil, India, Taiwan, China and 3 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody (time frame: 26 weeks of study treatment). 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 7 Aug 2026.