Paroxysmal Nocturnal HemoglobinuriaPhase 3NCT03500549
Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
A Phase 3 study testing Pegcetacoplan and Soliris in people with Paroxysmal Nocturnal Hemoglobinuria, run by Apellis Pharmaceuticals, Inc. at 53 sites in 11 countries.
Trial summary
Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- Pegcetacoplan and Soliris
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 53 sitesin 11 countries
- Study dates
- 14 Jun 2018to 13 Aug 2020
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years of age
- Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
- On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
- Hb <10.5 g/dL at the Screening Visit
- Absolute reticulocyte count > 1.0x ULN at the Screening Visit
- Platelet count of >50,000/mm3 at the Screening Visit
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- Absolute neutrophil count >500/mm3 at the Screening Visit
- Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
- Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the Screening and Day -28 Visit (Run-in Period) and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug
- Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug
- Willing and able to give informed consent
- Willing and able to self-administer APL-2 (administration by caregiver will be allowed)
- Have a body mass index (BMI) ≤35.0 kg/m2
Who cannot join
- Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2)
- Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
- Hereditary complement deficiency
- History of bone marrow transplantation
- History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
- Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
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- Currently breast-feeding women
- Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk of participating in the study or confound the outcome of the study
- This study includes cardiac safety evaluations. The following cardiac eligibility criteria are necessary to avoid confounding the cardiac safety outcomes:
- History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death
- Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2
- QTcF > 470 ms, PR > 280 ms
- Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities
- Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening
- Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stable dose for less than 3 weeks prior to dosing
- Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than one week prior to the first dose of study medication (must have a repeat screening ECG after one week of prophylactic antibiotics with QTcF < 470 ms)
Trial locations and contacts
53 sites in 11 countries.
53 sites in 11 countries
United States19 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Roswell Park Cancer Institute
Buffalo, New York, 14263
Northwestern University
Chicago, Illinois, 60611
Good Samaritan Hospital
Corvallis, Oregon, 97330
Denver Health
Denver, Colorado, 80204
Duke University Medical Center
Durham, North Carolina, 27710
New York Cancer & Blood Specialists
East Setauket, New York, 11733
Cancer & Hematology Centers of Western Michigan
Grand Rapids, Michigan, 49503
Investigative Clinical Research of Indiana
Indianapolis, Indiana, 46260
Cancer Specialists of North Florida
Jacksonville, Florida, 32256
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
University of Southern California
Los Angeles, California, 90033
Baptist Cancer Center
Memphis, Tennessee, 38120
Lakes Research
Miami Lakes, Florida, 33014
Mid Florida Hematology and Oncology
Orange City, Florida, 32763
Sarcoma Oncology Research Center
Santa Monica, California, 90403
New York Cancer & Blood Specialists
The Bronx, New York, 10469
HOPE Cancer Center of East Texas
Tyler, Texas, 75701
Georgetown University Hospital
Washington D.C., District of Columbia, 20057
France8 sites
Centre Hospitalier Annecy Genevois
Annecy, 74374
Centre Hospitalier William Morey
Chalon-sur-Saône, 71100
Centre Hospitalier Universitaire de Lille
Lille, 59037
Institut Paoli-Calmettes Marseille
Marseille, 13009
Hôpital Saint-Louis
Paris, 75010
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Centre Hospitalier de Saint-Quentin
Saint-Quentin, 02321
Institut Universitaire du Cancer Toulouse - Oncopole
Toulouse, 31059
Japan8 sites
Juntendo University Hospital
Bunkyo-ku, Tokyo, 113-8421
Shinshu University Hospital
Matsumoto, Nagano, 390-8621
Japanese Red Cross Nagoya Daiichi Hospital
Nagoya, Aichi-ken, 453-8511
Okayama University Hospital
Okayama, Okayama-ken, 700-8558
NTT Medical Center Tokyo
Shinagawa-ku, Tokyo, 141-8625
Japanese Red Cross Nagoya Daini Hospital
Showa-ku, Aichi-ken, 453-8650
Kinan Hospital
Tanabe, Wakayama, 646-8588
University of Tsukuba Hospital
Tsukuba, Ibaraki, 305-8576
Germany4 sites
Uniklinik RWTH Aachen
Aachen, North Rhine-Westphalia, 52074
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, 45147
Universitätsklinikum Hamburg Eppendorf
Hamburg, 20246
Universitätsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
Russia3 sites
Pavlov First Saint Petersburg State Medical University of Russian Ministry of Health
Saint Petersburg, 197022
Pavlov First Saint Petersburg State Medical University
Saint Petersburg, 197022
Institution of Health Care of Tyumen Region
Tyumen, 625023
South Korea3 sites
Soonchunhyang University Bucheon Hospital
Bucheon-si, 14584
Chungnam National University Hospital
Daejeon, 35015
Samsung Medical Center
Seoul, 06351
Belgium2 sites
AZ Delta Campus Wilgenstraat
Roeselare, West-Vlaanderen, 8800
Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert, Vlaams-Brabant, 1200
Canada2 sites
University of Alberta
Edmonton, Alberta, T6G 2G3
Toronto General Hospital
Toronto, Ontario, M9A1G2
Spain2 sites
Hospital Universitario de Gran Canaria Dr. Negrín
Las Palmas de Gran Canaria, 35010
Hospital Universitario Politécnico La Fe
Valencia, 46026
United Kingdom1 site
St. James' Institute of Oncology, Leeds Teaching Hospitals
Leeds, LS9 7TF
About this study
Official title: A Phase III, Randomized, Multi-Center, Open-Label, Active-Comparator Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- Pegcetacoplan, Soliris
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegcetacoplanDrug
Also called APL-2
Complement (C3) Inhibitor
SolirisDrug
Complement (C5) Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Pegcetacoplan | Experimental | 1080 mg pegcetacoplan administered subcutaneously twice-weekly or every three days. Receives: Drug: Pegcetacoplan; Drug: Soliris |
| Eculizumab | Active comparator | Complement (C5) Inhibitor. Receives: Drug: Pegcetacoplan; Drug: Soliris |
What is being measured
The primary outcome is the main question the study is designed to answer.
Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 16
Secondary outcomes (25)
Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP
Subjects who experienced more than 1 transfusion during the RCP are only counted once. Subjects who did not have a transfusion but withdrew before Week 16 were considered as having a transfusion in the analysis of transfusion avoidance.
Measured: Day 1 to Week 16
LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP
The FACIT-fatigue scale version 4 is a 13-item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. A higher score corresponds to a higher quality of life (QoL). Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.
Measured: Baseline and Week 16
Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16
Hb response was defined as an increase of at least 1 g/dL in Hb from Baseline at Week 16. Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 16
Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16
Reticulocyte normalization was defined as the ARC being below the upper limit of the gender-specific normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 were classified as nonresponders.
Measured: Week 16
Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16
Hb normalization was defined as the Hb level being above the lower limit of the normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 are classified as nonnormalization.
Measured: Week 16
LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP
The LASA consists of 3 items, where the respondents were asked to rate their perceived level of functioning. Specific domains included activity level, ability to carry out daily activities, and an item for overall QoL. Their level of functioning was reported on a 0 to 100 scale with 0 indicates "As low as could be" and 100 indicates "As high as could be". The combined score ranged from 0 to 300, with higher scores corresponding to a higher QoL.
Measured: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Scale (QLQ-C30) Scores During the RCP
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are "Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Measured: Baseline and Week 16
Total Number of PRBC Units Transfused During the RCP
Subjects who withdrew during the RCP before Week 16 will have their number of units of PRBC estimated from the duration they were in the study.
Measured: Day 1 to Week 16
Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 48
Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Week 17 and Week 48
Mean Change From Baseline to Week 48 in ARC During the Treatment Period
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 48
Mean Change From Week 17 to Week 48 in ARC During the Open-label Period
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Week 17 and Week 48
Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Baseline and Week 48
Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Measured: Week 17 and Week 48
Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period
The FACIT-fatigue scale version 4 is a 13-item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. A higher score corresponds to a higher QoL. Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.
Measured: Baseline and Week 48
Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period
The FACIT-fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher QoL.
Measured: Week 17 and Week 48
Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period
The LASA consists of 3 items, where the respondents were asked to rate their perceived level of functioning. Specific domains included activity level, ability to carry out daily activities, and an item for overall QoL. Their level of functioning was reported on a 0 to 100 scale with 0 indicates "As low as could be" and 100 indicates "As high as could be". The combined score ranged from 0 to 300, with higher scores corresponding to a higher QoL.
Measured: Baseline and Week 48
Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period
The FACIT-fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher QoL.
Measured: Week 17 and Week 48
Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are 'Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Measured: Baseline and Week 48
Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are designated by functional scales, symptom scales, and global subject QoL/overall perceived health status. For the first 28 questions the 4 possible responses are 'Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Measured: Week 17 and Week 48
Total Number of PRBC Units Transfused During the Open-Label Period
Number of units of PRBC transfused to subjects in the open-label period are reported.
Measured: Week 17 to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2018
- Study start14 Jun 2018
- Primary completion14 Nov 2019
- Study completion13 Aug 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 (11)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Apellis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03500549
- Sponsor's protocol ID
- APL2-302
- Status last verified
- Mar 2022
- First submitted
- 10 Apr 2018
- Last updated
- 25 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
de Castro C, Kelly RJ, Griffin M, Patriquin CJ, Mulherin B, Hochsmann B, Selvaratnam V, Wong RSM, Hillmen P, Horneff R, Uchendu UO, Zhang Y, Surova E, Szamosi J, de Latour RP. Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan. Adv Ther. 2025 Sep;42(9):4641-4658. doi: 10.1007/s12325-025-03310-8. Epub 2025 Jul 28.
PubMed 40720060de Latour RP, Kulasekararaj A, Dingli D, Wilson K, Wojciechowski P, Hakimi Z, Nazir J, Czech B, Hillmen P, Szer J. Anchored Indirect Treatment Comparison Finds Comparable Effects of Pegcetacoplan and Iptacopan in Paroxysmal Nocturnal Haemoglobinuria. Eur J Haematol. 2025 Aug;115(2):125-133. doi: 10.1111/ejh.14422. Epub 2025 Apr 25.
PubMed 40285403Panse J, Daguindau N, Okuyama S, Peffault de Latour R, Schafhausen P, Straetmans N, Al-Adhami M, Persson E, Wong RSM. Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin >/=10 g/dL) who had received eculizumab or were naive to complement inhibitors. PLoS One. 2024 Jul 29;19(7):e0306407. doi: 10.1371/journal.pone.0306407. eCollection 2024.
PubMed 39079163Mulherin BP, Yeh M, Al-Adhami M, Dingli D. Normalization of Hemoglobin, Lactate Dehydrogenase, and Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan. Drugs R D. 2024 Jun;24(2):169-177. doi: 10.1007/s40268-024-00463-9. Epub 2024 May 10.
PubMed 38727860Peffault de Latour R, Griffin M, Kelly RJ, Szer J, de Castro C, Horneff R, Tan L, Yeh M, Panse J. Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2024 Jun 11;8(11):2718-2725. doi: 10.1182/bloodadvances.2024012672.
PubMed 38593241Sharma V, Koprivnikar J, Drago K, Savage J, Bachelor A. Injection Site Reactions with Long-Term Pegcetacoplan Use in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Brief Report. Adv Ther. 2023 Nov;40(11):5115-5129. doi: 10.1007/s12325-023-02653-4. Epub 2023 Sep 14.
PubMed 37707673de Latour RP, Szer J, Weitz IC, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro CM, Nishimori H, Ajayi T, Al-Adhami M, Deschatelets P, Francois C, Grossi F, Risitano AM, Hillmen P. Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial. Lancet Haematol. 2022 Sep;9(9):e648-e659. doi: 10.1016/S2352-3026(22)00210-1.
PubMed 36055332Cella D, Sarda SP, Hsieh R, Fishman J, Hakimi Z, Hoffman K, Al-Adhami M, Nazir J, Cutts K, Lenderking WR. Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study. Ann Hematol. 2022 Sep;101(9):1905-1914. doi: 10.1007/s00277-022-04887-8. Epub 2022 Jul 23.
PubMed 35869984Hakimi Z, Wilson K, McAughey E, Pochopien M, Wojciechowski P, Toumi M, Knight C, Sarda SP, Patel N, Wiseman C, de Castro NP, Nazir J, Kelly RJ. The cost-effectiveness, of pegcetacoplan compared with ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria, in a UK setting. J Comp Eff Res. 2022 Sep;11(13):969-985. doi: 10.2217/cer-2022-0076. Epub 2022 Jul 7.
PubMed 35796199Bhak RH, Mody-Patel N, Baver SB, Kunzweiler C, Yee CW, Sundaresan S, Swartz N, Duh MS, Krishnan S, Sarda SP. Comparative effectiveness of pegcetacoplan versus ravulizumab in patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a matching-adjusted indirect comparison. Curr Med Res Opin. 2021 Nov;37(11):1913-1923. doi: 10.1080/03007995.2021.1971182. Epub 2021 Sep 3.
PubMed 34445916Hillmen P, Szer J, Weitz I, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, Peffault de Latour R. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021 Mar 18;384(11):1028-1037. doi: 10.1056/NEJMoa2029073.
PubMed 33730455
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Multi-Center, Open-Label, Active-Comparator Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
- ClinicalTrials.gov ID
- NCT03500549
- Acronym / sponsor ID
- APL2-302
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Apellis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Jun 2018 (actual)
- Primary completion
- 14 Nov 2019 (actual)
- Study completion
- 13 Aug 2020 (actual)
- First posted
- 18 Apr 2018 (actual)
- Results
- Posted 25 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pegcetacoplan | Experimental | Drug: Pegcetacoplan, Drug: Soliris1080 mg pegcetacoplan administered subcutaneously twice-weekly or every three days. |
| Eculizumab | Active comparator | Drug: Pegcetacoplan, Drug: SolirisComplement (C5) Inhibitor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- At least 18 years of age
- Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
- On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
- Hb <10.5 g/dL at the Screening Visit
- Absolute reticulocyte count > 1.0x ULN at the Screening Visit
Key exclusion criteria (16 listed)
- Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2)
- Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
- Hereditary complement deficiency
- History of bone marrow transplantation
- History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
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 |
|---|---|---|
| PegcetacoplanAlso: APL-2Complement (C3) Inhibitor | Drug | Eculizumab, Pegcetacoplan |
| SolirisComplement (C5) Inhibitor | Drug | Eculizumab, Pegcetacoplan |
Primary outcome
Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP
Time frame: Baseline and Week 16
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
25 secondary outcomes
Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP
Time frame: Day 1 to Week 16
LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP
Time frame: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP
Time frame: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP
Time frame: Baseline and Week 16
Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16
Time frame: Baseline and Week 16
Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16
Time frame: Week 16
Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16
Time frame: Week 16
LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP
Time frame: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP
Time frame: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP
Time frame: Baseline and Week 16
LS Mean Change From Baseline to Week 16 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Scale (QLQ-C30) Scores During the RCP
Time frame: Baseline and Week 16
Total Number of PRBC Units Transfused During the RCP
Time frame: Day 1 to Week 16
Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period
Time frame: Baseline and Week 48
Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period
Time frame: Week 17 and Week 48
Mean Change From Baseline to Week 48 in ARC During the Treatment Period
Time frame: Baseline and Week 48
Mean Change From Week 17 to Week 48 in ARC During the Open-label Period
Time frame: Week 17 and Week 48
Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period
Time frame: Baseline and Week 48
Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period
Time frame: Week 17 and Week 48
Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period
Time frame: Baseline and Week 48
Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period
Time frame: Week 17 and Week 48
Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period
Time frame: Baseline and Week 48
Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period
Time frame: Week 17 and Week 48
Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period
Time frame: Baseline and Week 48
Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period
Time frame: Week 17 and Week 48
Total Number of PRBC Units Transfused During the Open-Label Period
Time frame: Week 17 to Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40720060de Castro C, Kelly RJ, Griffin M, Patriquin CJ, Mulherin B, Hochsmann B, Selvaratnam V, Wong RSM, Hillmen P, Horneff R, Uchendu UO, Zhang Y, Surova E, Szamosi J, de Latour RP. Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan. Adv Ther. 2025 Sep;42(9):4641-4658. doi: 10.1007/s12325-025-03310-8. Epub 2025 Jul 28.
- Derived from this study: PubMed 40285403de Latour RP, Kulasekararaj A, Dingli D, Wilson K, Wojciechowski P, Hakimi Z, Nazir J, Czech B, Hillmen P, Szer J. Anchored Indirect Treatment Comparison Finds Comparable Effects of Pegcetacoplan and Iptacopan in Paroxysmal Nocturnal Haemoglobinuria. Eur J Haematol. 2025 Aug;115(2):125-133. doi: 10.1111/ejh.14422. Epub 2025 Apr 25.
- Derived from this study: PubMed 39079163Panse J, Daguindau N, Okuyama S, Peffault de Latour R, Schafhausen P, Straetmans N, Al-Adhami M, Persson E, Wong RSM. Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin >/=10 g/dL) who had received eculizumab or were naive to complement inhibitors. PLoS One. 2024 Jul 29;19(7):e0306407. doi: 10.1371/journal.pone.0306407. eCollection 2024.
- Derived from this study: PubMed 38727860Mulherin BP, Yeh M, Al-Adhami M, Dingli D. Normalization of Hemoglobin, Lactate Dehydrogenase, and Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan. Drugs R D. 2024 Jun;24(2):169-177. doi: 10.1007/s40268-024-00463-9. Epub 2024 May 10.
- Derived from this study: PubMed 38593241Peffault de Latour R, Griffin M, Kelly RJ, Szer J, de Castro C, Horneff R, Tan L, Yeh M, Panse J. Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2024 Jun 11;8(11):2718-2725. doi: 10.1182/bloodadvances.2024012672.
- Derived from this study: PubMed 37707673Sharma V, Koprivnikar J, Drago K, Savage J, Bachelor A. Injection Site Reactions with Long-Term Pegcetacoplan Use in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Brief Report. Adv Ther. 2023 Nov;40(11):5115-5129. doi: 10.1007/s12325-023-02653-4. Epub 2023 Sep 14.
- Derived from this study: PubMed 36055332de Latour RP, Szer J, Weitz IC, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro CM, Nishimori H, Ajayi T, Al-Adhami M, Deschatelets P, Francois C, Grossi F, Risitano AM, Hillmen P. Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial. Lancet Haematol. 2022 Sep;9(9):e648-e659. doi: 10.1016/S2352-3026(22)00210-1.
- Derived from this study: PubMed 35869984Cella D, Sarda SP, Hsieh R, Fishman J, Hakimi Z, Hoffman K, Al-Adhami M, Nazir J, Cutts K, Lenderking WR. Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study. Ann Hematol. 2022 Sep;101(9):1905-1914. doi: 10.1007/s00277-022-04887-8. Epub 2022 Jul 23.
- Derived from this study: PubMed 35796199Hakimi Z, Wilson K, McAughey E, Pochopien M, Wojciechowski P, Toumi M, Knight C, Sarda SP, Patel N, Wiseman C, de Castro NP, Nazir J, Kelly RJ. The cost-effectiveness, of pegcetacoplan compared with ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria, in a UK setting. J Comp Eff Res. 2022 Sep;11(13):969-985. doi: 10.2217/cer-2022-0076. Epub 2022 Jul 7.
- Derived from this study: PubMed 34445916Bhak RH, Mody-Patel N, Baver SB, Kunzweiler C, Yee CW, Sundaresan S, Swartz N, Duh MS, Krishnan S, Sarda SP. Comparative effectiveness of pegcetacoplan versus ravulizumab in patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a matching-adjusted indirect comparison. Curr Med Res Opin. 2021 Nov;37(11):1913-1923. doi: 10.1080/03007995.2021.1971182. Epub 2021 Sep 3.
- Derived from this study: PubMed 33730455Hillmen P, Szer J, Weitz I, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, Peffault de Latour R. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021 Mar 18;384(11):1028-1037. doi: 10.1056/NEJMoa2029073.
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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.
53 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pegcetacoplan and Soliris in people with Paroxysmal Nocturnal Hemoglobinuria, run by Apellis Pharmaceuticals, Inc. at 53 sites in 11 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 13 inclusion and 16 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 25 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, France, Japan, Germany, Russia and 6 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?
Yes. Results are posted in the registry (first posted 25 Mar 2022). 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?
Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP (time frame: Baseline and Week 16). 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 NCT03500549, which also lists 11 linked publications.
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 25 Mar 2022.