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

NCT04073498 | Completed Phase 1

• 1 other identifier: AP-0101
• Study Type: interventional
• Target: 39
• Locations: 3 countries
• Sites: 3

Brief 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 Georgia. 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.

Conditions

Hemophilia a; Hemophilia B

Outcome Measures

Primary Outcomes (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

  From Day 1 up to 74 weeks

Secondary Outcomes (16)

• PK of SerpinPC in plasma after single dose administration - Cmax

  From Day 1 up to 26 weeks

• PK of SerpinPC in plasma after single dose administration - Tmax

  From Day 1 up to 26 weeks

• PK of SerpinPC in plasma after single dose administration - kel

  From Day 1 up to 26 weeks

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

  From Day 1 up to 26 weeks

• PK of SerpinPC in plasma after single dose administration - AUC

  From Day 1 up to 26 weeks

Other Outcomes (2)

• Effect of SerpinPC on Annualised Bleeding Rate and factor usage

  From Day 1 up to 26 weeks

• Effect of SerpinPC on Annualised Bleeding Rate following extended monthly dosing

  From Day 1 up to 74 weeks

Study Arms (14)

Part 1a - Cohort 1

EXPERIMENTAL

A single IV infusion of 0.0003 mg/kg SerpinPC in healthy subjects.

Drug: SerpinPC

Part 1a - Cohort 2

EXPERIMENTAL

A single IV infusion of 0.001 mg/kg SerpinPC in healthy subjects.

Drug: SerpinPC

Part 1a - Cohort 3

EXPERIMENTAL

A single IV infusion of 0.003 mg/kg SerpinPC in healthy subjects.

Drug: SerpinPC

Part 1a - Cohort 4

EXPERIMENTAL

A single IV infusion of 0.01 mg/kg SerpinPC in healthy subjects.

Drug: SerpinPC

Part 1a - Cohort 5

EXPERIMENTAL

A single SC dose of 0.03 mg/kg SerpinPC and a single SC dose of placebo in healthy subjects.

Drug: SerpinPC; Drug: Placebo

Part 1b - Cohort 6

EXPERIMENTAL

A single SC dose of 0.1 mg/kg SerpinPC and a single SC dose of placebo in patients.

Drug: SerpinPC; Drug: Placebo

Part 1b - Cohort 7

EXPERIMENTAL

A single SC dose of 0.3 mg/kg SerpinPC and a single SC dose of placebo in patients.

Drug: SerpinPC; Drug: Placebo

Part 1b - Cohort 8

EXPERIMENTAL

A single SC dose of 0.6 mg/kg SerpinPC and a single SC dose of placebo in patients.

Drug: SerpinPC; Drug: Placebo

Part 1b - Cohort 9

EXPERIMENTAL

Two single SC doses of 0.6 mg/kg SerpinPC in patients.

Drug: SerpinPC

Part 2

EXPERIMENTAL

Up 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.

Drug: SerpinPC; Drug: Placebo

Part 3

EXPERIMENTAL

A 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.

Drug: SerpinPC

Part 4

EXPERIMENTAL

SC 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.

Drug: SerpinPC

Part 5

EXPERIMENTAL

SC 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.

Drug: SerpinPC

Part 6

EXPERIMENTAL

A 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.

Drug: SerpinPC

Interventions

SerpinPC DRUG

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

Part 1a - Cohort 1; Part 1a - Cohort 2; Part 1a - Cohort 3; Part 1a - Cohort 4; Part 1a - Cohort 5; Part 1b - Cohort 6; Part 1b - Cohort 7; Part 1b - Cohort 8; Part 1b - Cohort 9; Part 2; Part 3; Part 4; Part 5; Part 6

Placebo DRUG

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

Part 1a - Cohort 5; Part 1b - Cohort 6; Part 1b - Cohort 7; Part 1b - Cohort 8; Part 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• Patient is unable to tolerate SerpinPC.

Sponsors & Collaborators

• ApcinteX Ltd: lead
• Centessa Pharmaceuticals plc: collaborator

Study Sites (3)

Arensia Clinical Research Unit

Tbilisi, 0112, Georgia

Location

Arensia Clinical Research Unit

Chisinau, Moldova

Location

Simbec Research Ltd

Merthyr Tydfil, Cardiff, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Part 1a: Open label for intravenous (IV) doses and single blinded for SC doses (subjects are blinded) Part 1b: Single blinded (patients are blinded) Part 2: Open label Part 3: Open label Part 4: Open label Part 5: Open label Part 6: Open label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 29, 2019
• Study Start: August 14, 2019
• Primary Completion: September 26, 2024
• Study Completion: September 26, 2024
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); MO (1); GE (1)