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PNHPhase 2NCT03593200

A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH

A Phase 2 study testing Pegcetacoplan in people with PNH, run by Apellis Pharmaceuticals, Inc. at 3 sites in 2 countries.

Completed

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

Official record
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Trial summary

This is a Phase IIa, open-label, multiple dose, study in patients with PNH who have not received eculizumab (Soliris ®) in the past. A single cohort of subjects is planned for evaluation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
PNH
What is being tested?
Pegcetacoplan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
3 sitesin 2 countries
Study dates
16 Aug 2018to 22 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • At least 18 years old (inclusive)
  • Diagnosed with PNH (white blood cell (WBC) clone >10%)
  • Lactose dehydrogenase (LD) ≥2 times the upper limit of normal
  • Screening Ferritin ≥ normal and Total Iron Binding Capacity (TIBC) < LLN based on central lab reference ranges. If a subject is receiving iron supplements at screening, the investigator must ensure that his/her dose has been stable for 8 weeks prior to enrolment and must be maintained throughout the study
  • Last transfusion within 12 months prior to screening
  • Platelet count of >30,000/mm3 at the screening visit
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  • Absolute neutrophil count >500/ mm3 at the screening visit
  • Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study
  • Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study
  • 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 pegcetacoplan. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
  • Willing and able to give informed consent

Who cannot join

  • Prior eculizumab (Soliris®) treatment
  • Active bacterial infection
  • Hereditary complement deficiency
  • History of bone marrow transplantation
  • Concurrent severe aplastic anemia (SAA), defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or anti-thymocyte globulin
  • Participation in any other investigational drug trial or exposure to another investigational agent, device or procedure within 30 days
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  • Evidence of QTcF prolongation defined as >450 ms for males and >470 ms for females at screening
  • Breast-feeding women
  • History of meningococcal disease

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Bulgaria2 sites

  • Acibadem City Clinic MHAT Tokuda EAD Sofia

    Sofia

  • Specialized Hospital for Active Treatment of Hematologic Diseases EAD, Sofia

    Sofia

Other trials in Bulgaria

Serbia1 site

  • Klinički centar Srbije

    Belgrade

Other trials in Serbia

About this study

Official title: Phase IIa, Open Label, Multiple Dose Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).

This is a Phase IIa, open-label, multiple dose, study in patients with PNH who have not received eculizumab (Soliris ®) in the past. A single cohort of subjects is planned for evaluation.

Conditions
PNH
Being tested
Pegcetacoplan
Keywords
PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, Hemolysis, Hematologic diseases, Extravascular hemolysis (EVH), Intravascular hemolysis (IVH), C3 inhibitor
Medical subject headings
Hemoglobinuria, Paroxysmal, Anemia, Hemoglobinuria, Hemolysis, Hematologic Diseases

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

Study groups in NCT03593200
Study groupRoleWhat they receive
Experimental: Cohort 1Experimental270 mg/day (up to 360 mg/day from Day 29) from Day 1 to Day 364*
Receives: Drug: Pegcetacoplan

What is being measured

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

  1. Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity

    TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possible, probable, or definite. TEAEs were graded according to the Common Terminology Criteria for Adverse Events (v4.03) based on: Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening, Grade 5: Death related to AE.

    Measured: From Day 1 to 30 days after the last dose (approximately 56 weeks)

  2. Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level

    Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.

    Measured: Baseline and Day 365

  3. Mean Change From Baseline in Haptoglobin Level

    Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.

    Measured: Baseline and Day 365

  4. Mean Change From Baseline in Hemoglobin (Hb) Level

    Hematology assessments of Hb were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.

    Measured: Baseline and Day 365

Secondary outcomes (8)

  1. Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score

    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 quality of life (QoL).

    Measured: Baseline and Day 365

  2. Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level

    Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.

    Measured: Baseline and Day 365

  3. Mean Change From Baseline in Total Bilirubin Level

    Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.

    Measured: Baseline and Day 365

  4. Mean Number of Red Blood Cell (RBC) Transfusions Per Month

    The number of on-study RBC transfusions was monitored throughout the treatment period.

    Measured: From Day 1 to Day 364

  5. Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL

    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 Day 365

  6. Mean Serum Concentrations of Pegcetacoplan

    Serum concentrations of pegcetacoplan at Day 365 are presented.

    Measured: Day 365

  7. Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal)

    The AUCtotal of pegcetacoplan was estimated using a non-compartmental approach.

    Measured: Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.

  8. Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total)

    The Ctrough,max,total of pegcetacoplan was estimated using a non-compartmental approach.

    Measured: Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.

Timeline

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

  1. First posted20 Jul 2018
  2. Study start16 Aug 2018
  3. Primary completion22 Oct 2019
  4. Study completion22 Oct 2019

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03593200
Sponsor's protocol ID
APL2-202
Status last verified
Dec 2020
First submitted
28 Jun 2018
Last updated
22 Dec 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Wong RSM, Pullon HWH, Amine I, Bogdanovic A, Deschatelets P, Francois CG, Ignatova K, Issaragrisil S, Niparuck P, Numbenjapon T, Roman E, Sathar J, Xu R, Al-Adhami M, Tan L, Tse E, Grossi FV. Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria. Ann Hematol. 2022 Sep;101(9):1971-1986. doi: 10.1007/s00277-022-04903-x. Epub 2022 Jul 22.

    PubMed 35869170

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pegcetacoplan in people with PNH, run by Apellis Pharmaceuticals, Inc. at 3 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 11 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 22 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Bulgaria, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2020). 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 With Treatment Emergent Adverse Events (TEAEs) Including by Severity (time frame: From Day 1 to 30 days after the last dose (approximately 56 weeks)). The study lists 4 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 NCT03593200, 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 22 Dec 2020.

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