Pharmacokinetics and pharmacodynamics of once-weekly administration of JR-142, a long-acting albumin-fused human growth hormone: A rondemized, placebo-controlled phase 1 study

Article

Author: Hirato, Tohru ; Yamamoto, Ryuji ; Ikeda, Toshiaki ; Minami, Kohtaro ; Okazaki, Mika ; Mita, Yoko ; Yamamoto, Tatsuyoshi ; Sato, Yuji ; Takahashi, Kenichi ; Tanizawa, Kazunori ; Sonoda, Hiroyuki ; Owada, Yasuko

OBJECTIVE:

Under clinical development for patients with growth hormone deficiency, JR-142 is a long-acting growth hormone with a half-life extended by fusion with modified serum albumin. We conducted a Phase 1 study to investigate the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of once-weekly subcutaneous administrations of JR-142. The study consisted of two parts: an open-label single ascending dosing study (Part 1), and a randomized, placebo-controlled, assessor-blinded multiple ascending dosing study (Part 2).

DESIGN:

A total of 31 healthy Japanese male participants were enrolled. In Part 1, seven of them received a single subcutaneous injection of JR-142 each at dosages of 0.15 mg/kg (n = 1), 0.25 mg/kg (n = 2), 0.5 mg/kg (n = 2), or 1.0 mg/kg (n = 2). In Part 2, one weekly subcutaneous injection of JR-142 at 0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg or a placebo were given for four weeks to each of the other 24 participants (six in each group). Plasma JR-142 and serum insulin-like growth factor-1 (IGF-1) concentrations were measured for PK and PD assessments. Safety was evaluated on the basis of adverse events (AEs), laboratory tests, and other measures.

RESULTS:

JR-142 induced dose-dependent increases in the maximum plasma JR-142 concentration (C_max) and the area under the plasma concentration-time curve from time 0 to τ (AUC_0-τ). A similar dose-response relationship was observed in serum IGF-1 concentrations. All trough IGF-1 levels were well sustained one week after the final administrations of JR-142 at the three dosages, while the peak concentrations of IGF-1 remained mildly elevated. No serious AEs were observed, and laboratory tests, including assessment of anti-drug antibodies, uncovered no significant safety issues.

CONCLUSIONS:

Once-weekly subcutaneous injections of JR-142 produced positive dose-dependent PK and PD profiles over the dosage range. Drug accumulation was observed after the four-week administration period but did not raise safety concerns, indicating that JR-142 is well-tolerated in healthy participants. The PD profiles observed in terms of IGF-1 concentrations were also positive, and we believe the encouraging results of this study warrant substantiation in further clinical trials in patients with GHD.

ETHICS:

This clinical study was conducted at one investigational site in Osaka, Japan, where the clinical study and the non-clinical data of JR-142 were reviewed and approved by its Institutional Review Board on 9th May 2019. The study was conducted in compliance with the approved study protocol, the Declaration of Helsinki, 1964, as revised in 2013, and Good Clinical Practice.

News (Medical) associated with Redalsomatropin alfa

20 Dec 2024

·pipelinereview.com

JCR Pharmaceuticals Initiates Phase III Clinical Trial of JR-142 in Japan, a Long-Acting Growth Hormone Therapy

HYOGO, Japan I December 20, 2024 I JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”) today announced that the first patient has been dosed in the Phase III clinical trial of JR-142 (INN: redalsomatropin alfa) in Japan, marking a significant milestone in the development of this innovative treatment. JR-142 is a long-acting growth hormone therapy and is being studied in patients with pediatric growth hormone deficiency. The trial involves 54 pediatric patients and will compare the efficacy of JR-142 to JCR’s existing product, Growject ® . Patients will receive treatment over a 52-week period, with growth outcomes serving as the primary measure of success. Detailed trial information is available through Japan Register of Clinical Trials ( jRCT2031240282 ). “I am thrilled to see progress in the development of treatments for pediatric patients,” said Professor Noriyuki Namba, Division of Pediatrics and Perinatology at Tottori University Faculty of Medicine, and the Medical Expert of the study. “Growth hormone therapy typically requires daily injections, but JR-142, as a long-acting therapy, offers the possibility of once-weekly dosing. This advancement has the potential to significantly ease the burden on children and their families, improving both convenience and quality of care while maintaining high safety standards.” JCR remains committed to the growth hormone field by ensuring a stable supply of high-quality pharmaceuticals and expanding treatment options to meet diverse patient needs. About Growject ® Growject ® is an injectable preparation containing recombinant human growth hormone, first launched in Japan by JCR in 1995. The dosage is administered subcutaneously 6–7 times per week, adjusted according to the indicated condition. About JCR Pharmaceuticals Co., Ltd. JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceuticals company that is expanding possibilities for people with rare and genetic diseases worldwide. We continue to build upon our 49-year legacy in Japan while expanding our global footprint into the US, Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. JCR strives to expand the possibilities for patients while accelerating medical advancement at a global level. Our core values – reliability, confidence, and belief – benefit all our stakeholders, including patients, partners, and employees. For more information, please visit https://www.jcrpharm.co.jp/en/site/en/ . SOURCE: JCR Pharmaceuticals

Phase 3Phase 2

100 Deals associated with Redalsomatropin alfa

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Growth hormone deficiency	Phase 3	JP	JCR Pharmaceuticals Co., Ltd.	20 Dec 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis