AzTrials
AzTrials

Paroxysmal Nocturnal HemoglobinuriaPhase 3NCT04085601

A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With PNH

A Phase 3 study testing APL-2 in people with Paroxysmal Nocturnal Hemoglobinuria, run by Apellis Pharmaceuticals, Inc. at 30 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Evaluation of the Efficacy and Safety of Pegcetacoplan 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?
APL-2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
30 sitesin 10 countries
Study dates
27 Aug 2019to 23 Jun 2021
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

  • Be at least 18 years old (inclusive).
  • Have LDH ≥1.5 x ULN at the screening visit.
  • Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or monocyte clone >10%).
  • Have Hb less than the lower limit of normal (LLN) at the screening visit.
  • Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less than/equal to ULN at the screening visit, based on central laboratory reference ranges. If a subject is receiving iron supplements at screening, the Investigator must ensure that the subject's dose has been stable for 4 weeks prior to screening, and it must be maintained throughout the study. Subjects not receiving iron at screening must not start iron supplementation during the course of the study.
  • Body mass index (BMI) ≤ 35 kg/m2 at the screening visit.
  • Have a platelet count of >50,000/mm3 at the screening visit.
  • Have an absolute neutrophil count >500/mm3 at the screening visit.

Who cannot join

  • Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to screening.
  • Hereditary complement deficiency.
  • History of bone marrow transplantation.
  • Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time period indicated below prior to screening:
  • Erythropoietin or immunosuppressants for at least 8 weeks
  • Systemic corticosteroids for at least 4 weeks
Show all 9Show fewer
  • Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least 4 weeks
  • Iron supplements, vitamin B12, or folic acid for at least 4 weeks
  • Low-molecular-weight heparin for at least 4 weeks

Trial locations and contacts

30 sites in 10 countries.

30 sites in 10 countries

Thailand8 sites

  • Ramathibodi Hospital

    Bangkok, 10400

  • Siriraj Hospital

    Bangkok, 10700

  • Hospital for Tropical disease

    Bangkok

  • Phramongkutklao Hospital

    Bangkok

  • Maharaj Nakorn Chiang Mai Hospital

    Chiang Mai, 50200

  • Srinagaring Hospital

    Khon Kaen, 40002

  • Thammasat University Hospital

    Pathum Thani, 12120

  • Songklanagaring Hospital

    Songkhla, 90110

Other trials in Thailand

Philippines6 sites

  • Baguio General Hospital

    Benguet, 2600

  • Perpetual Succour Hospital

    Cebu City, 6000

  • Mary Mediatrix Medical Center

    Lipa City, 4217

  • Makati Medical Centre

    Makati City, 1229

  • The Medical City

    Pasig, 1604

  • St. Lukes Medical Centre

    Quezon City, 1112

Other trials in Philippines

Hong Kong3 sites

  • Queen Mary Hospital

    Hong Kong

  • Princess Margaret Hospital

    Kwai Chung

  • Prince and Wales Hospital

    Shatin

Other trials in Hong Kong

Peru3 sites

  • Hospital Cayetano Heredia

    Jesús María, Lima, 15072

  • Hospital Nacional Dos de Mayo

    Lima, 15003

  • Hospital Cayetano Heredia

    San Martín de Porres, Lima region, 15102

Other trials in Peru

Poland3 sites

  • Independent Public Clinical Hospital

    Lubin, 20-081

  • Institute of Hematology and Transfusiology

    Warsaw, 02-776

  • EMC Medical Institute

    Wroclaw, 50-220

Other trials in Poland

Colombia2 sites

  • Julian Coronel Medical Center

    Cali

  • Research Center of the Colombian Clinical Life Cancer Foundation

    Medellín

Other trials in Colombia

Malaysia2 sites

  • Hospital Ampang

    Ampang, Selangor, 68000

  • University Malaya Medical Centre

    Kuala Lumpur, 59100

Other trials in Malaysia

Mexico1 site

  • Hospital Universitario Dr.Jose Eleuterio Gonzalez

    Monterrey

Other trials in Mexico

Serbia1 site

  • Clinical Centre of Serbia

    Belgrade

Other trials in Serbia

Singapore1 site

  • Singapore General Hospital (SGH)

    Singapore, 169608

Other trials in Singapore

About this study

Official title: A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Evaluation of the Efficacy and Safety of Pegcetacoplan in Patients with Paroxysmal Nocturnal Hemoglobinuria .

Being tested
APL-2
Medical subject headings
Hemoglobinuria, Paroxysmal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APL-2Drug

    Complement (C3) Inhibitor

Study groups in NCT04085601
Study groupRoleWhat they receive
Standard of Care (SOC) excluding complement inhibitorsNo interventionNot described
1,080mg APL-2 administered subcutaneously twice weeklyExperimentalNot described
Receives: Drug: APL-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects Who Achieved Hemoglobin (Hb) Stabilization

    The Hb stabilization was defined as avoidance of a >1 gram per deciliter (g/dL) decrease in Hb concentration from Baseline in the absence of transfusion through Week 26.

    Measured: From Baseline (Day 1) up to Week 26

  2. Change From Baseline in Lactate Dehydrogenase (LDH) Concentration At Week 26

    The LDH concentration was analyzed using an analysis of covariance (ANCOVA) model with a last observation carried forward (LOCF) and a baseline observation carried forward (BOCF) approach for handling missing data. Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.

    Measured: Baseline (Day 1) and Week 26

Secondary outcomes (14)

  1. Number of Subjects With an Hb Response in the Absence of Transfusions

    An Hb response was defined as a =>1 g/dL increase in Hb from baseline at Week 26.

    Measured: Baseline and Week 26

  2. Change From Baseline in Absolute Reticulocyte Count (ARC) at Week 26

    Blood samples were collected via direct venipuncture at the specific time points to determine ARC. Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.

    Measured: Baseline and Week 26

  3. Change From Baseline in Hb Concentration at Week 26

    Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.

    Measured: Baseline and Week 26

  4. Percentage of Subjects Who Received Transfusion or Decrease of Hb >2 g/dL From Baseline

    Transfusion refers to any transfusion of PRBC, leukocyte-depleted red blood cells (LDPRC), leukocyte poor packed red blood cell (LPRC), leukocyte poor blood (LPB) or whole blood.

    Measured: At Week 26

  5. Percentage of Subjects With Transfusion Avoidance

    Transfusion avoidance was defined as the percentage of subjects who did not require a transfusion during the RCP. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.

    Measured: At Week 26

  6. Number of PRBC Units Transfused From Baseline Through Week 26

    The number of units of PRBC transfusions was estimated. In one transfusion subjects received one or more units.

    Measured: Up to Week 26

  7. Change From Baseline in Functional Assessment of Chronic Illness Therapy- (FACIT-Fatigue) Scale Score at Week 26

    The FACIT-Fatigue Scale is a 13-item Likert scaled instrument that is self-administered by the subjects during clinic visits. Subjects were presented with 13 statements and asked to indicate their responses as it applied to the past 7 days. The 5 possible responses are "Not at all" (0), "A little bit" (1), "Somewhat" (2), "Quite a bit" (3), and "Very much" (4). With 13 statements, the total score has a range of 0 to 52. The higher score corresponded to a higher quality of life. Baseline is defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.

    Measured: Baseline and Week 26

  8. Percentage of Subjects With Hb Normalization Levels at Week 26

    Normalization of Hb levels defined as >= 1x LLN at Week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.

    Measured: Baseline and Week 26

  9. Percentage of Subjects With LDH Normalization at Week 26

    The LDH normalization was defined as LDH <= 1xupper limit of normal (ULN) of normal range at week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPPRC, LPRC, LPB or whole blood.

    Measured: At Week 26

  10. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30) Scores at Week 26

    The EORTC QLQ-C30 questionnaire (version 3.0) consisted of 30 questions comprised of both multi-item scales and single-item measures to assess overall quality of life in subjects. Questions were 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'). Each scale has a range of 0% - 100%. A high scale score represents a higher response level. Baseline is defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.

    Measured: Baseline and Week 26

  11. Change From Baseline in Linear Analog Assessment (LASA) Scales Score at Week 26

    The LASA consisted of 3 items asking respondents to rate their perceived level of functioning. Specific domains include activity level, ability to carry out daily activities, and an item for overall QOL. Their level of functioning was reported on a 0-100 scale with 0 representing "As low as could be" and 100 representing "As high as could be".

    Measured: Baseline and Week 26

  12. Percentage of Subjects With ARC Normalization

    Absolute reticulocyte count normalization is defined as ARC < 1x ULN of the gender-specific normal range at week 26 in the absence of transfusion. Subjects who received a transfusion or withdraw from study or escaped from SoC to pegcetacoplan treatment group or lost to follow up without providing efficacy data at Week 26 were classified as non-responders. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.

    Measured: At Week 26

  13. Number of Subjects With Failure of Hb Stabilization

    Hb stabilization is defined as avoidance of a >1 g/dL decrease in Hb levels from baseline through Week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.

    Measured: Up to Week 26

  14. Time to First PRBC Transfusion

    Time to first-on-study PRBC transfusions during RCP were reported. Here NA indicates not estimable.

    Measured: Up to Week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2019
  2. Study start27 Aug 2019
  3. Primary completion23 Jun 2021
  4. Study completion23 Jun 2021

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04085601
Sponsor's protocol ID
APL2-308
Status last verified
Oct 2022
First submitted
9 Sep 2019
Last updated
21 Oct 2022
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 40720060

  • Panse 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 39079163

  • Mulherin 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 38727860

  • Fishman J, Wilson K, Drzewiecka A, Pochopien M, Dingli D. The cost-effectiveness of pegcetacoplan in complement treatment-naive adults with paroxysmal nocturnal hemoglobinuria in the USA. J Comp Eff Res. 2023 Oct;12(10):e230055. doi: 10.57264/cer-2023-0055. Epub 2023 Sep 1.

    PubMed 37655691

  • Wojciechowski P, Wdowiak M, Hakimi Z, Wilson K, Fishman J, Nazir J, Toumi M. Mapping the EORTC QLQ-C30 onto the EQ-5D-5L index for patients with paroxysmal nocturnal hemoglobinuria in France. J Comp Eff Res. 2023 May;12(5):e220178. doi: 10.57264/cer-2022-0178. Epub 2023 Apr 13.

    PubMed 37052120

  • Wong RSM, Navarro-Cabrera JR, Comia NS, Goh YT, Idrobo H, Kongkabpan D, Gomez-Almaguer D, Al-Adhami M, Ajayi T, Alvarenga P, Savage J, Deschatelets P, Francois C, Grossi F, Dumagay T. Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2023 Jun 13;7(11):2468-2478. doi: 10.1182/bloodadvances.2022009129.

    PubMed 36848639

  • Wong R, Fishman J, Wilson K, Yeh M, Al-Adhami M, Zion A, Yee CW, Huynh L, Duh MS. Comparative Effectiveness of Pegcetacoplan Versus Ravulizumab and Eculizumab in Complement Inhibitor-Naive Patients with Paroxysmal Nocturnal Hemoglobinuria: A Matching-Adjusted Indirect Comparison. Adv Ther. 2023 Apr;40(4):1571-1589. doi: 10.1007/s12325-023-02438-9. Epub 2023 Feb 7.

    PubMed 36750531

  • Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.

    PubMed 34922648

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing APL-2 in people with Paroxysmal Nocturnal Hemoglobinuria, run by Apellis Pharmaceuticals, Inc. at 30 sites in 10 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 8 inclusion and 9 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 21 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 30 sites in Thailand, Philippines, Hong Kong, Peru, Poland and 5 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 21 Oct 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?

Number of Subjects Who Achieved Hemoglobin (Hb) Stabilization (time frame: From Baseline (Day 1) up to Week 26). 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 NCT04085601, which also lists 8 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 21 Oct 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in