Journey to success in Phase 1b Clinical Study for Hepatitis B at the University Malaya Medical Centre, Malaysia

By Chan Wei Quan, Site Manager, Global Clinical Operations (GCO) Malaysia, Janssen

Prof Rosmawati and her team, together with CIC and Janssen representatives.

If you were diagnosed with chronic hepatitis B, would you be willing to try an experimental compound developed by a world-renowned pharmaceutical company? On one hand, you may be hesitant but on the other, you may want to know more about it. For novel compounds to be approved for use in the market, pharmaceutical companies go through a period of pre-clinical and clinical phases to evaluate the compound’s effectiveness. To achieve this, volunteers are needed!

Based on statistics generated by Clinical Research Malaysia (CRM) on phases of clinical trials that were conducted in Malaysia for the year of 2017, Phase 3 studies topped the chart. Whereas for Phase 1 studies, a total of 5 Phase 1b studies were conducted in Malaysia. Is Malaysia too reserved in exploring Phase 1 studies? As a matter of fact, Malaysia has recently released a Phase 1 clinical guideline as well as a Phase 1-unit inspection and accreditation program. Malaysia is now one step closer to conducting more first-in-human (Phase 1) research. Thanks to the groups of regional key opinion leaders in initiating the Phase 1 realization project (P1RP), afflicted patients in Malaysia now have access to new treatment options and regimens. Furthermore, this allows room for economic growth as clinical research could be one of its main drivers as mentioned by the previous Malaysian Health Minister, Dr. Subramaniam. A little elaboration on what Phase 1 study is. Phase 1 study is to primarily to determine what dosage is safe and how treatment should be given. Dosage may be given in single ascending dose/multiple ascending dose. The target population is usually healthy volunteer and study is conducted in small scale. You may search for “Phase 1” to know more……

Chronic Hepatitis B (CHB) is one of the most alarming diseases that has captured the attention of the public health globally. One of the common infections by the hepatitis virus, CHB is often linked with major psychosocial issues due to social stigma. In Malaysia, a multicultural country in Asia, the CHB carries rate varies depending on ethnicity and gender. According to Raihan R (2016), CHB accounts for more than 80% of the hepatocellular carcinoma (HCC) cases seen in Malaysia, and HCC is the third most common type of malignant neoplasm and among the top ten leading causes of death. Following the implementation of the nationwide hepatitis B vaccination in 1989, there was a steady decline of CHB. There is currently no cure to hepatitis B and CHB patients require a daily medication regimen to suppress the hepatitis B viral load. This duration of this regimen is indefinite with the risk of patients developing side effects over the long run. There is an unmet medical need to a CHB cure and this has been the central focus of many pharmaceutical companies. There are several pharmaceutical companies working to develop a cure for CHB. Any of these companies wanting to conduct a trial in Malaysia would know that Prof Dr. Rosmawati Mohamed is a leading key opinion leader in this field.

L-R: Prof Dr Rosmawati awarded the “Top recruiter In Asia – Phase 1b: Session XI” and Dr Syed Mukhtar awarded with certificate of appreciation in ensuring study quality.

While managing the Phase 1b trial (namely HPB1001) clinical study in Malaysia, I had the privilege of working with a renowned hepatologist from the University Malaya Medical Centre (UMMC), Prof. Rosmawati Mohamed. The novel compound may or may not confer therapeutic benefits to the patient, however, the eagerness to look for a functional cure and to improve CHB patients’ quality of life for Prof Rosmawati prevailed. Prof Rosmawati as the principal investigator (PI) headed a team comprising Dr. Roma Basu and Dr. Abdul Malik (sub-investigators), in addition to Dr. Syed Mukhtar and Dr. Zainab Abu Kassim (study coordinators). During this time, Prof. Rosmawati and her team dedicated valuable time and effort in screening for suitable patients. Patients needed to be diagnosed with CHB, but also had to be relatively well in terms of medical health. Furthermore, patients needed adhere to protocol procedures and restrictions while being compliant to prohibited and allowed concomitant medications. At the end of the recruitment period, Prof Rosmawati and her team managed to recruit five patients into the HPB1001 study, ranking Malaysia as the second-best recruiter globally, and ahead of a few countries known for well-established Phase 1 experiences. This achievement puts Malaysia in the limelight as a rising competitive country in conducting Phase 1b trials, despite being initially considered naïve country in Phase 1 studies.

Clinical trials are unable to commence without the approval from a local ethics committee (EC). Moreover, clinical trial proposals submitted to the EC may sometimes warrant justification from the PI on the risk-benefit assessment for conducting such a clinical trial (termed a EC defense meeting). The HPB2001 trial was one of the proposals requiring further clarification, for which Prof. Rosmawati defended excellently. Her effort in defending the proposal during the meeting ensured that the study was approved by the EC on time, allowing for country and global milestones to be met.

Another important aspect of clinical trials is the generation of quality data. Data is collected each time the patient makes a visit to the hospital. This data is compiled and analyzed on a global level, allowing further adjustments to protocols as required. This data is eventually required for the submission to the health authorities for drug approval and marketing. For the HPB2001 trial, Pros. Rosmawati showed great perseverance in ensuring the timely entry of patient data as well as implementing effective retention strategies for the patient during the three-month study period. Prof. Rosmawati managed to retain all of her enrolled patients in the HPB2001 clinical study, symbolizing a mark of excellence.

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In this highly regulated industry, subject safety, data integrity and quality are of the utmost importance. In August 2018, the Malaysia Health Authorities, the National Pharmaceutical Regulatory Agency (NPRA) conducted a three-day inspection for the HPB1001 at UMMC. The outcome was favorable with no major findings or observations noted. The results of this inspection are not only a reflection of Prof. Rosmawati’s dedication to conducting the HPB2001 trial but is also a form of favorable validation on the quality of the research. Furthermore, the success of the inspection is also attributed to the Clinical Investigation Centre (CIC), a clinical department at UMMC dedicated to conducting clinical trials.

Clinical research is a necessary step in sourcing alternative treatment options to many diseases. CHB is one of these diseases. The success of clinical research is largely dependent on the clinical study team chosen to manage it. However, aside from the study team, an even more pivotal element in ensuring the success of clinical trials are the patients. Patients who join the trials allow the generation of data, which in turns leads to more data contributing to the approval of the drug and eventually its availability to the community, hence bringing more benefit to more patients. The willingness of patients who volunteer in the early drug development phase is deserving of commending respect, despite the limited safety and efficacy data generated from pre-clinical studies. Their commitment to clinical trials is regarded as a major contribution in accelerating the development and approval of experimental treatment options. The “I AM AWARE” campaign, designed to increase awareness of clinical research in Malaysia is currently underway. These campaigns conduct regular roadshows at government hospitals and also happen to be a good source of information pertaining to clinical research.

Raihan R. Hepatitis in Malaysia: Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):52-55