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Hemophilia aPhase 1/2NCT04073498

The Safety and Tolerability of SerpinPC in Healthy Men and in Men with Severe Blood Disorders (haemophilia a and B)

A Phase 1/2 study testing SerpinPC in people with Hemophilia a and Hemophilia B, run by ApcinteX Ltd at 3 sites in 3 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

The purpose of this study is to investigate the safety and activity in the body of a new drug called SerpinPC. The study will be split into 7 parts: Part 1a will be conducted in healthy male volunteers in the UK (up to 15) and Parts 1b, 2, 3, 4, 5 and 6 will be conducted in haemophilia A \& B patients in Moldova and… Read more about this study

Who is it for?
Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for
Hemophilia a, Hemophilia B
What is being tested?
SerpinPC
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
39 participants
Where
3 sitesin 3 countries
Study dates
14 Aug 2019to 26 Sep 2024
Phase
Phase 1/2
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 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Part 1a (Healthy Subjects)
  • Males age ≥18 years and ≤55 years.
  • Capable of giving written informed consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or delegate.
  • Willingness to give written consent to have data entered into The Over-volunteering Prevention System (TOPS).
  • Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of the entire trial.
  • Screening D-dimer ≤ 750 µg/L
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  • Non-user of nicotine products i.e. non-smokers or ex-smokers who have stopped smoking or who had stopped using cigarette replacements for at least 6 months before the first dose of IMP.
  • Male subject willing to use 2 highly effective methods of contraception from the first dose administration until 3 months after dosing.
  • Subject with a body mass index (BMI) of 18 - 30 kg/m2 and weight ≥ 60 kg.
  • Subject with no clinically significant history of previous drug allergies.
  • Subject with no clinically significant abnormal Cytokine levels (IL6 and TNFα), serum biochemistry, haematology, coagulation and urinalysis within 28 days before the first dose of IMP.
  • Subject with negative urinary drugs of abuse (DOA) and alcohol screens, determined within 28 days before the first dose of IMP (N.B. A positive test result may be repeated at the Investigator's discretion).
  • Subject with negative human immunodeficiency virus (HIV), and hepatitis B surface antigen (HBsAg) and/or hepatitis C virus antibody (HCV Ab) test results at Screening.
  • Subject with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 28 days before the first dose of IMP.
  • Subject with no clinically significant abnormalities in vital signs (supine blood pressure/pulse rate, oral temperature) determined within 28 days before the first dose of IMP.
  • Subject must be available to complete the study (including all follow up visits).
  • Subject must satisfy an Investigator about his fitness to participate in the study.
  • Part 1b and Part 2 (Patients)
  • Male age ≥18 years and ≤60 years.
  • Capable of giving written informed consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the Investigator or delegate.
  • Patients with severe haemophilia (defined as having factor VIII/IX ≤ 0.02 IU/mL [2%]) with or without inhibitors, with an ABR (annualised bleeding rate) of 6 or more during the Observational Phase.
  • Patients on demand therapy with fVIII, fIX, rfVIIa (NovoSeven), FEIBA for treatment of bleeding.
  • Screening D-dimer ≤ 750 μg/L (DDU).
  • Adequate haematologic function, defined as having platelet count ≥ 100,000/μL (≥ 100 x 109/L) and haemoglobin ≥ 12 g/dL (≥ 120 g/L or ≥ 7.45 mmol/L) at the time of Screening and prior to the first dose administration.
  • Adequate hepatic function, defined as having total bilirubin ≤ 1.5x ULN (excluding Gilbert's syndrome) and AST and/or ALT ≤ 3x ULN at the time of Screening and prior to the first dose administration; no clinical signs or known laboratory OR radiographic evidence consistent with cirrhosis of the liver.
  • Adequate renal function, defined as having serum creatinine ≤ 2.5x ULN at the time of Screening and prior to the first dose administration.
  • Part 3 (patients who have completed Week 24 of Part 2)
  • Completed Week 24 of Part 2 with no major compliance issues.
  • Capable of giving written informed consent to participate after reading the information and consent form, and after having the opportunity to discuss the extension study with the Investigator or delegate.
  • Adaquate haematologic function, defined as having platelet count ≥ 100,000/μL and haemoglobin ≥ 8 g/dL (4.97 mmol/L) at Week 20 in Part 2.
  • Adequate hepatic function, defined as having total bilirubin ≤ 1.5x ULN (excluding Gilbert's syndrome) and AST and/or ALT ≤ 3x ULN at Week 20 in Part 2 with no clinical signs or known laboratory or radiographic evidence consistent with cirrhosis.
  • Adequate renal function, defined as serum creatinine ≤ 2.5x ULN at Week 20 in Part 2.
  • Part 4 (Patients who have completed Week 48 of Part 3):
  • Completed Week 48 of Part 3 with no major compliance issues.
  • Capable of giving written informed consent to participate after reading the information and consent form, and after having the opportunity to discuss the extension study with the Investigator or delegate.
  • Adequate haematologic function, defined as platelet count ≥ 100,000/μL and haemoglobin ≥ 8 g/dL (4.97 mmol/L) at Week 44 of Part 3.
  • Adequate hepatic function, defined as total bilirubin ≤ 1.5x ULN (excluding Gilbert's syndrome) and AST and/or ALT ≤ 3 x ULN at Week 44 of Part 3 with no clinical signs or known laboratory or radiographic evidence consistent with cirrhosis.
  • Adequate renal function, defined as serum creatinine ≤ 2.5x ULN at Week 44 of Part 3.
  • Part 5 (Patients who have completed Week 24 of Part 4):
  • Completed Week 24 of Part 4 with no major compliance issues.
  • Capable of giving written informed consent to participate after reading the information and consent form, and after having the opportunity to discuss the extension study with the Investigator or delegate.
  • Adequate haematologic function, defined as platelet count ≥ 100,000/μL and haemoglobin ≥ 8 g/dL(4.97 mmol/L) at Week 20 of Part 4.
  • Adequate hepatic function, defined as total bilirubin ≤ 1.5x ULN (excluding Gilbert's syndrome) and AST and/or ALT ≤ 3 x ULN at Week 20 of Part 4 with no clinical signs or known laboratory or radiographic evidence consistent with cirrhosis.
  • Adequate renal function, defined as serum creatinine ≤ 2.5x ULN at Week 20 of Part 4.
  • Part 6 (Patients who have completed Week 52 of Part 5):
  • Completed Week 52 of Part 5 with no major compliance issues.
  • Capable of giving written informed consent to participate after reading the information and consent form, and after having the opportunity to discuss the extension study with the Investigator or delegate.
  • Adequate haematologic function, defined as platelet count ≥ 100,000/μL and haemoglobin ≥ 8 g/dL (4.97 mmol/L) at Week 48 of Part 5.
  • Adequate hepatic function, defined as total bilirubin ≤ 1.5x ULN (excluding Gilbert's syndrome) and AST and/or ALT ≤ 3 x ULN at Week 48 of Part 5 with no clinical signs or known laboratory or radiographic evidence consistent with cirrhosis.
  • Adequate renal function, defined as serum creatinine ≤ 2.5x ULN at Week 48 of Part 5.

Who cannot join

  • Healthy subject/patient with known thrombophilia.
  • Healthy subject/patient with previous Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), Myocardial Infarction (MI) or stroke.
  • Healthy subject/patient with uncontrolled hypertension (healthy subject: Systolic BP > 140 mmHg, Diastolic BP > 90 mmHg and patient: Systolic BP > 160 mmHg, Diastolic BP > 100 mmHg).
  • Healthy subject/patient with diagnosis of diabetes requiring drug treatment.
  • Healthy subject/patient who has active cancer or requiring therapy for cancer or diagnosis of cancer in previous 12 months before the first dose of IMP.
  • Healthy subject who has participated in a clinical trial during the 90 days prior to dosing and patient who has participated in a clinical trial during the 30 days prior to screening.
Show all 32Show fewer
  • Healthy subject/patient with any major medical or psychological or psychiatric condition that could cause the healthy subject/patient to be unsuitable for the study or could interfere with the interpretation of the study results.
  • Healthy subject/patient with a history of or other evidence of recent alcohol or drug abuse (in the previous 12 months before the first dose of IMP).
  • Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
  • Inability to communicate well with Investigators (i.e., language problem, poor mental development or impaired cerebral function).
  • Donation of 450 mL or more blood within the 3 months before the first dose of IMP.
  • Additional Exclusion Criteria only applicable for Part 1b, Part 2, Part 3, Part 4 and Part 5:
  • Known HIV infection with CD4 count (or T-cell count) < 200 cells/μL within 24 weeks prior to screening.
  • Any other conditions or comorbidities, which in the opinion of the investigator would make the patient unsuitable for enrolment or could interfere with participation in or completion of the study.
  • Treatment with anticoagulant or antiplatelet drugs.
  • Additional Exclusion Criteria only applicable for Part 3:
  • Patient is unable to tolerate SerpinPC.
  • Patient with clinically significant safety data in Part 2 as determined by the Safety Review Committee or Investigator.
  • Patient with persistent high titre antidrug antibodies (ADAs) confirmed in Part 2 (up to Week 12 or Week 16).
  • Participation in a clinical trial, except Part 2, during the 30 days prior to Day 0.
  • Additional Exclusion Criteria only applicable for Part 4:
  • Patient is unable to tolerate SerpinPC.
  • Patient with clinically significant safety data in Part 3 as determined by the Safety Review Committee or Investigator.
  • Participation in a clinical trial, except Part 3, during the 30 days prior to Day 0.
  • Additional Exclusion Criteria only applicable for Part 5:
  • Patient is unable to tolerate SerpinPC.
  • Patient with clinically significant safety data in Part 4 as determined by the Safety Review Committee or Investigator.
  • Participation in a clinical trial, except Part 4, during the 30 days prior to Day 0.
  • Additional Exclusion Criteria only applicable for Part 6:
  • Patient is unable to tolerate SerpinPC.
  • Patient with clinically significant safety data in Part 5 as determined by the Safety Review Committee or Investigator.
  • Participation in a clinical trial, except Part 5, during the 30 days prior to Day 0.

Trial locations and contacts

3 sites in 3 countries.

3 sites in 3 countries

Georgia1 site
  • Arensia Clinical Research Unit

    Tbilisi, 0112

Other trials in Georgia

Moldova1 site
  • Arensia Clinical Research Unit

    Chisinau

Other trials in Moldova

United Kingdom1 site
  • Simbec Research Ltd

    Merthyr Tydfil, Cardiff, CF48 4DR

Other trials in United Kingdom

About this study

Official title: An Adaptive Design, Phase I/IIa, Open Label, Multicentre, Single Dose Escalation and Multiple Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of Intravenous and Subcutaneous Doses of SerpinPC in Healthy Male Volunteers and Male Participants with Severe Haemophilia a or B with or Without Inhibitors

The purpose of this study is to investigate the safety and activity in the body of a new drug called SerpinPC.

The study will be split into 7 parts: Part 1a will be conducted in healthy male volunteers in the UK (up to 15) and Parts 1b, 2, 3, 4, 5 and 6 will be conducted in haemophilia A \& B patients in Moldova and Georgia.

Read more

Part 1a of the study will look at how safe the drug is when given as single doses to healthy volunteers at different strengths and via 2 different routes of administration (through a vein or via an injection under the skin). Parts 1b, 2, 3, 4, 5 and 6 of the study will look at the safety of the drug when given as an injection under the skin to patients with severe haemophilia A or B.

The study will also investigate how the levels of the drug in the blood change over a period of time and how the drug acts in the body by taking blood samples. These blood samples will measure the concentration of the drug in the blood and measure certain aspects of the blood to determine how the drug affects them.

The study sponsor (ApcinteX) is developing this drug for the treatment of haemophilia A and haemophilia B, which are 2 types of rare blood disorders which affect the body's ability to form blood clots. Patients who have haemophilia A and B do not have certain clotting factors in their blood which means that they experience difficulty in stopping bleeding after injury and can be prone to extended periods of bleeding.

Current treatments for haemophilia involves injections which replace the missing factors in the blood. However these treatments are short term and therefore patients require regular treatments in order to manage the condition.

Therefore, there is a need to develop more effective treatments which provide longer term benefits. The aim of SerpinPC is to prevent bleeding rather than to have to treat bleeds to minimise pain and damage after they have occurred.

Being tested
SerpinPC, Placebo
Medical subject headings
Hemophilia A, Hemophilia B

What participants receive

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

  • SerpinPCDrug

    Administered as IV infusion (over 30 minutes) or SC injection (abdomen) according to cohort dosing instructions.

  • PlaceboDrug

    Matching placebo administered by SC injection according to cohort dosing instructions.

Study groups in NCT04073498
Study groupRoleWhat they receive
Part 1a - Cohort 1ExperimentalA single IV infusion of 0.0003 mg/kg SerpinPC in healthy subjects.
Receives: Drug: SerpinPC
Part 1a - Cohort 2ExperimentalA single IV infusion of 0.001 mg/kg SerpinPC in healthy subjects.
Receives: Drug: SerpinPC
Part 1a - Cohort 3ExperimentalA single IV infusion of 0.003 mg/kg SerpinPC in healthy subjects.
Receives: Drug: SerpinPC
Part 1a - Cohort 4ExperimentalA single IV infusion of 0.01 mg/kg SerpinPC in healthy subjects.
Receives: Drug: SerpinPC
Part 1a - Cohort 5ExperimentalA single SC dose of 0.03 mg/kg SerpinPC and a single SC dose of placebo in healthy subjects.
Receives: Drug: SerpinPC; Drug: Placebo
Part 1b - Cohort 6ExperimentalA single SC dose of 0.1 mg/kg SerpinPC and a single SC dose of placebo in patients.
Receives: Drug: SerpinPC; Drug: Placebo
Part 1b - Cohort 7ExperimentalA single SC dose of 0.3 mg/kg SerpinPC and a single SC dose of placebo in patients.
Receives: Drug: SerpinPC; Drug: Placebo
Part 1b - Cohort 8ExperimentalA single SC dose of 0.6 mg/kg SerpinPC and a single SC dose of placebo in patients.
Receives: Drug: SerpinPC; Drug: Placebo
Part 1b - Cohort 9ExperimentalTwo single SC doses of 0.6 mg/kg SerpinPC in patients.
Receives: Drug: SerpinPC
Part 2ExperimentalUp to 3 SC doses may be selected for Part 2 and each patient will be assigned a single SerpinPC dose level (and placebo). The dose for Part 2 will be determined from ongoing review of the Part 1 data. The dose in Part will not exceed 1.2 mg/kg, or the highest dose deemed safe from Part 1b.
Receives: Drug: SerpinPC; Drug: Placebo
Part 3ExperimentalA single flat SC dose of SerpinPC will be administered every 4 weeks for 48 weeks for patients who have completed Week 24 of Part 2. The dose level will be chosen after reviewing Part 2 data and will not exceed maximum dose level in Part 2.
Receives: Drug: SerpinPC
Part 4ExperimentalSC doses of 1.2 mg/kg SerpinPC will be administered every 2 weeks for 24 weeks for patients who have completed Week 48 of Part 3.
Receives: Drug: SerpinPC
Part 5ExperimentalSC doses of 1.2 mg/kg SerpinPC will be administered every 2 weeks for 52 weeks for patients who have completed Week 24 of Part 4.
Receives: Drug: SerpinPC
Part 6ExperimentalA single flat SC dose of 60mg SerpinPC will be administered every 2 weeks for 52 weeks for patients who have completed Week 52 of Part 5.
Receives: Drug: SerpinPC

What is being measured

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

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Number of Participants with One or More Drug Related Adverse Events (AEs) or any Serious AEs

    Measured: From Day 1 up to 74 weeks

Secondary outcomes (16)
  1. PK of SerpinPC in plasma after single dose administration - Cmax

    Maximal concentration

    Measured: From Day 1 up to 26 weeks

  2. PK of SerpinPC in plasma after single dose administration - Tmax

    Time of maximal concentration

    Measured: From Day 1 up to 26 weeks

  3. PK of SerpinPC in plasma after single dose administration - kel

    Elimination rate constant

    Measured: From Day 1 up to 26 weeks

  4. PK of SerpinPC in plasma after single dose administration - t1/2

    Terminal elimination half-life

    Measured: From Day 1 up to 26 weeks

  5. PK of SerpinPC in plasma after single dose administration - AUC

    Area under the concentration-time curve

    Measured: From Day 1 up to 26 weeks

  6. PK of SerpinPC in plasma after single dose administration - AUC0-t

    Area under the concentration-time curve from time of dosing to last measureable concentration

    Measured: From Day 1 up to 26 weeks

  7. PK of SerpinPC in plasma after single dose administration - AUC0-inf

    Area under the concentration-time curve from time of dosing extrapolated to infinity.

    Measured: From Day 1 up to 26 weeks

  8. PK of SerpinPC in plasma after single dose administration - AUC%

    Residual area under the concentration-time curve.

    Measured: From Day 1 up to 26 weeks

  9. PK following multiple dose administration - Cmax

    Maximal concentration

    Measured: From Day 1 up to 26 weeks

  10. PK following multiple dose administration - Tmax

    Time to maximal concentration

    Measured: From Day 1 up to 26 weeks

  11. PK following multiple dose administration - Kel

    Elimination rate constant

    Measured: From Day 1 up to 26 weeks

  12. PK following multiple dose administration - t1/2

    Terminal elimination half-life

    Measured: From Day 1 up to 26 weeks

  13. PK following multiple dose administration - AUC

    Area under the concentration-time curve

    Measured: From Day 1 up to 26 weeks

  14. PK following multiple dose administration - AUC(0-τ)

    Area under the concentration-time curve from time of dosing to the end of the dosing interval

    Measured: From Day 1 up to 26 weeks

  15. PK following multiple dose administration - R0

    Accumulation ratio

    Measured: From Day 1 up to 26 weeks

  16. PK following multiple dose administration - Ctrough

    Trough concentration

    Measured: From Day 1 up to 26 weeks

Timeline

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

  1. First posted29 Aug 2019
  2. Study start14 Aug 2019
  3. Primary completion26 Sep 2024
  4. Study completion26 Sep 2024

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
The study will be conducted in 7 parts (Part 1a, Part 1b, Part 2, Part 3, Part 4, Part 5 and Part 6). Part 1a will be a single ascending dose study in 15 healthy male subjects. Part 1b will be a single ascending dose study in a minimum of 12 male patients with severe hemophilia A or B with or without inhibitors. Part 2 will involve subcutaneous doses not exceeding 1.2 mg/kg SerpinPC every 4 weeks in patients with severe hemophilia A or B with or without inhibitors. Part 3 will involve subcutaneous doses of SerpinPC in patients who have completed Week 24 of Part 2. Part 4 will involve subcutaneous doses of 1.2 mg/kg SerpinPC every 2 weeks for 24 weeks in patients who have completed Week 48 of Part 3. Part 5 will involve subcutaneous doses of 1.2 mg/kg SerpinPC every 2 weeks for 52 weeks for patients who have completed Week 24 of Part 4. Part 6 will involve a subcutaneous flat dose of 60mg SerpinPC every 2 weeks for 52 weeks for patients who have completed Week 52 of Part 5.
Masking
Single blind
Who is masked
Participant
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04073498
Sponsor's protocol ID
AP-0101
Status last verified
Feb 2025
First submitted
13 Aug 2019
Last updated
6 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing SerpinPC in people with Hemophilia a and Hemophilia B, run by ApcinteX Ltd at 3 sites in 3 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 50 inclusion and 32 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 6 Feb 2025. 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 Georgia, Moldova, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

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

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

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?

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: From Day 1 up to 74 weeks). 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 6 Feb 2025.

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