Evaluation of the safety and efficacy of biosimilar recombinant growth hormone in children with growth hormone deficiency: non-inferiority, randomized, parallel, multicentric and Phase III trial

ABSTRACT

Objectives

This study is designed in order to compare the efficacy and safety of recombinant human growth hormone (rhGH) with the reference brand.

Methods

According to the inclusion criteria, 85 people in 13 Iranian centers were randomly selected to receive biosimilar Somatropin (Somatin®) (44 people) and reference Somatropin (Norditropin®) (41 people) at a dose of 35 µg/kg/d, seven days/week for 12 months. The primary outcomes included height velocity (HV) was measured during 12 months of treatment.

Results

The two intervention groups’ Height changes were similar. The mean HV was 10.96 cm/year in the biosimilar group and 10.05 cm/year in the reference groups after 12 months. Estimates of the lower bounds of 95% CI for mean height differences in the biosimilar intervention group compared to the reference intervention group did not exceed the 2 cm margin. Therefore, the non-inferiority of biosimilar intervention compared to the brand product is verified. Common ADRs in both groups were nausea in two patients (2.4%), diarrhea in two patients (2.4%), increased body temperature in one patient (1.2%), and headache in one patient (1.2%).

Conclusions

The finding of this study indicated that Somatin® and Norditropin® have comparable efficacy and safety profiles.

Clinical trial registration

www.IRCT.irIRCT20171122037571N1.

KEYWORDS:

• Human growth hormone
• growth hormone deficiency
• biosimilar
• Phase III
• efficacy
• safety

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

H Zaeri was responsible as Principal investigator for study conduct based on GCP principles, study design, forming a team with the required experience for the study, taking care of the patients and collecting the data. M Hashemipour, P Eshraghi, S Arefnia, R Ghergherehchi, F Soheilipour, S Dalili, S Nourian, E Maleki, H Morravej, A Dideban, M Ghasemi and H Kharazmi were responsible by study conduction, taking care of the patients and collecting the data. N Khademolreza, MA Afshari, H Amini and S Ghaznavi were responsible for monitoring activities and interpretation of the data. A Akhlaghi was responsible for the Software and interpretation of the data. N Servatian was responsible for the interpretation of the data and manuscript writing. M Shahbazi, S Omidvar and B Taghavi were responsible by medical quality check of the data and review of the manuscript. All authors have read and approved the final version of the manuscript.

Acknowledgments

We thank the patients who participated in the study and all investigators for their contribution. We thank MA Afshari (Sponsor’s representative). We thank Trial Research Company, affiliated with the clinical trial center of Tehran University of Medical Sciences (CTC) as a Contract Research Organization (CRO). We thank M Razaghiazar, M Salek-Ardestani, A Ahmadi (CRO representative), Kazeminia (FDA Organization representative), Darboy (FDA Organization representative) and Bahmani (Ethics Committee representative) for Data and Safety Monitoring Board (DSMB).

Ethical statement

The present study has been conducted according to the ICH GCP Helsinki principles and Iran’s ethical and legal principles. Ensuring the confidentiality of the participants in the study is mentioned in the informed consent form and will also be communicated to them orally. All patients’ personal information and medical history are stored in an independent place with limited access except for authorized personnel or competent legal authorities only (if required).

Additional information

Funding

This study (www.IRCT.ir, IRCT20171122037571N1 (2022-09-13)) was funded by Arya Tina Gene biopharmaceutical company. The Arya Tina Gene biopharmaceutical company had no role in the study design, data collection, analysis, or interpretation, writing, or decision to submit the article for publication.