A study of safety and PK of SerpinPC in healthy male volunteers
Research type
Research Study
Full 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.
IRAS ID
264247
Contact name
Annelize Koch
Contact email
Sponsor organisation
ApcinteX
Eudract number
2019-001421-28
Duration of Study in the UK
0 years, 5 months, 15 days
Research summary
Research 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 3 parts: Part 1a will be conducted in healthy male volunteers in the UK (up to 15) and Parts 1b and 2 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).
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.Summary of Results
The purpose of this study was to investigate the study drug SerpinPC in healthy male participants and male participants with Haemophilia A and Haemophilia B, which are 2 types of rare blood disorders which affect the body’s ability to form blood clots. The main objectives of this study were to assess the safety and tolerability of SerpinPC when given as single doses at different strengths, via 2 different routes of administration (through a vein or via an injection under the skin) and over an extended period of time in both healthy volunteers and patients with haemophilia. The study also evaluated the levels of the study drug and how these levels of the drug in the blood change over a period of time and how the drug acts in the body. The study was conducted in 6 parts as follows:
Part 1a was conducted in 15 healthy male volunteers (split into 5 groups of 3 participants) with each group evaluating a different dose strength of SerpinPC as either an intravenous (IV) dose or a subcutaneous (SC) dose.
Part 1b was conducted in 12 male participants (split into 4 groups of 3 participants) with severe haemophilia A or B with or without inhibitors with each group evaluating a different dose strength of SerpinPC as a subcutaneous dose.
Part 2 was conducted in 23 male participants with severe haemophilia A or B with or without inhibitors (approximately 7 participants per dose level, up to 3 dose levels) who received a single SC dose of SerpinPC and/or a single SC dose of placebo every 4 weeks for 20 weeks.
Part 3 was an optional part of the study where 22 male participants with severe haemophilia A or B who had tolerated SerpinPC with no safety concerns in Part 2 received a monthly SC dose of SerpinPC. A single flat dose (i.e., not dependent on weight) of SerpinPC was administered SC every 4 weeks for 48 weeks (up to 13 doses).
Part 4 was an optional part of the study where 21 male participants with severe haemophilia A or B who had tolerated SerpinPC and completed Week 48 in Part 3 received a 1.2 mg/kg dose of SerpinPC administered SC every 2 weeks for 24 weeks (up to 13 doses).
Part 5 was an optional part of the study where 20 in male participants with severe haemophilia A or B who had tolerated SerpinPC and completed Week 24 in Part 4 received a 1.2 mg/kg dose of SerpinPC administered SC every 2 weeks for 52 weeks (up to 27 doses).
Part 6 was an optional part of the study where 16 male participants with severe haemophilia A or B who had tolerated SerpinPC and completed Week 52 in Part 5 received a single flat dose of 60 mg SerpinPC administered SC every 2 weeks for 52 weeks (up to 27 doses).
With respect to objectives of the study, the following outcomes were reported:
- Across all of the dose levels evaluated during the study, ranging from 0.0003 mg/kg to 0.1 mg/kg IV infusion and 0.03 mg/kg SC (healthy volunteers only) and 0.1 mg/kg to 0.6 mg/kg SC and 60 mg SC (patients with severe haemophilia only), SerpinPC was considered to be safe and well tolerated. No new safety signals were identified that changed the safety profile of SerpinPC.
- With respect to side effects which emerged during the course of treatment, no effects were reported for more than 1 participant in Parts 1a, 1b and 2. Across Parts 3 to 6, the most commonly reported effects were increases in certain markers associated with liver function which were considered to be expected in line with patients with severe haemophilia.
- The majority of side effects reported were mild or moderate in severity and with the exception of 2 events reported in Part 2, all effects were considered unrelated to unlikely related to study treatment.
- Overall, there were no notable trends in laboratory safety data (haematology, biochemistry, coagulation and cytokine levels, vital signs findings, physical examination findings, ECG results (Parts 1a, 1b and 2 only) or concomitant medications and there were no notable differences in between participants at the different dosing regimens.
In summary, the data gathered during the study were considered sufficient to meet the objectives of the study.
REC name
Wales REC 1
REC reference
19/WA/0176
Date of REC Opinion
22 Jul 2019
REC opinion
Further Information Favourable Opinion