A Clinical Pharmacology Study to Evaluate the Effect of GYM329 on Disuse Muscle Atrophy in Healthy Volunteer

NCT04708847 | Completed Phase 1 FDA Drug

• 1 other identifier: JP42791
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will induce disuse atrophy through unilateral immobilization of the thigh and lower leg in healthy male volunteers to evaluate the PD of a single subcutaneous dose of GYM329 prior to or after unilateral thigh and lower leg immobilization. Healthy male volunteers will receive either GYM329 or placebo by subcutaneous injection at two time points, before and after 2 weeks of unilateral thigh and lower leg immobilization, in an investigator- and subject-blinded, randomized, placebo-controlled, parallel-group design. At enrollment, all subjects will be randomized in a 1:2 ratio to either the pre-immobilization active drug group receiving a single subcutaneous dose of GYM329 before unilateral thigh and lower leg immobilization (Group A) or the pre-immobilization placebo group receiving a single subcutaneous dose of placebo before unilateral thigh and lower leg immobilization (Group B). On Day 15, subjects assigned to Group B and who completed the muscle strength assessment at Day15 will be further randomized in a 1:1 ratio to either the post-immobilization active drug group (Group B-1) or the post-immobilization placebo group (Group B-2). Group A will receive GYM329 on Day 1 and placebo on Day 15. Group B will receive placebo on Day 1. Subsequently, Group B-1 will receive GYM329 on Day 15 and Group B-2 will receive placebo on Day 15. Muscle strength will be measured at pre-immobilization of unilateral thigh and lower leg, post-immobilization of unilateral thigh and lower leg (Day 15), Day 29, and Day 43. Subjects will be observed for 252 days after the second study treatment administration (266 days after the first study treatment administration).

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Thigh muscle strength score

  Percent change in thigh muscle strength score from Day 1 to Day 15 and Day 15 to Day 29 (Thigh muscle strength score: peak isometric knee extension torque and peak isokinetic knee extension torque at 90°/s and 180°/s)

  28 days

Secondary Outcomes (12)

• Safety; Adverse event monitoring

  45 weeks

• Safety; Laboratory tests

  45 weeks

• Safety; Vital signs

  45 weeks

• Safety; Electrocardiogram (ECG)

  45 weeks

• Pharmacokinetics; Serum GYM329 concentrations

  45 weeks

Study Arms (3)

Pre-immobilization active drug group

EXPERIMENTAL

Subjects will receive a single subcutaneous dose of GYM329 on Day 1 and a single subcutaneous dose of placebo on Day 15.

Drug: GYM329

Post-immobilization active drug group

EXPERIMENTAL

Subjects will receive a single subcutaneous dose of placebo on Day 1 and a single subcutaneous dose of GYM329 on Day 15.

Drug: GYM329

Placebo group

PLACEBO COMPARATOR

Subjects will receive a single subcutaneous dose of placebo on Day 1 and a single subcutaneous dose of placebo on Day 15.

Drug: Placebo

Interventions

GYM329 DRUG

GYM329 subcutaneous injection

Post-immobilization active drug group; Pre-immobilization active drug group

Placebo DRUG

Placebo subcutaneous injection

Placebo group

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to provide written informed consent and to comply with the study protocol
• Healthy men aged from 18 to less than 40 years at the time of consent
• Right leg dominant
• Agreed to limit physical activity as directed by study site staff from the time of informed consent until the end of the muscle strength evaluation period (completion of Day 43)
• BMI is between 18.5 and less than 25.0 at screening
• Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.

You may not qualify if:

• History of congenital myopathy
• Congenital thrombophilia
• Previous or current VTE
• History of hip or limb surgery, spine or spinal cord surgery, or laparotomy (excluding laparotomy for appendicitis or inguinal hernia), or laparoscopic surgery (e.g. cholecystectomy)
• History of fracture of the pelvis or open/compound fracture of lower limb, or history of fracture within 3 years prior to screening, excluding digit fracture
• History of severe trauma, trauma requiring surgical intervention, or trauma with organ injury which deemed as clinically significant by the investigator
• Previous or current medical condition that could lead to thrombosis as judged by the investigator
• Angiography within 6 months before first study treatment administration
• Current Grade ≥ 3 thermal burn or history of Grade ≥ 3 thermal burn within 3 months prior to study treatment administration
• Unable to wear compression stockings
• History of heparin-induced thrombocytopenia or hypersensitivity to the LMWH and to the heparin or any other clinically significant contra-indications for use of LMWH
• Participation in bodybuilding or full time employment in a physically demanding occupation
• Immobilization, surgery, or traumatic injury of the arm within 90 days before first study treatment administration
• Traumatic injury of the leg within 6 months before first study treatment administration
• Immobilization or surgery of the leg within 6 months before first study treatment administration

Sponsors & Collaborators

• Chugai Pharmaceutical: lead

Study Sites (1)

QPS Netherlands B.V.

Groningen, 9713, Netherlands

Location

Study Officials

• Sponsor Chugai Pharmaceutical Co. Ltd

  clinical-trials@chugai-pharm.co.jp

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2020
• First Posted: January 14, 2021
• Study Start: February 10, 2021
• Primary Completion: June 3, 2022
• Study Completion: February 1, 2023
• Last Updated: February 17, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)