A Phase Ia Trial Comparing the Pharmacokinetics/Pharmacodynamics, Safety, and Preliminary Efficacy of HHK001 and Enantone in Patients With Endometriosis

NCT07793162 | Not Yet Recruiting Phase 1

• 1 other identifier: HHK001-1a
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study compares the pharmacokinetics/pharmacodynamics (PK/PD), safety, and preliminary efficacy of a single 3.75 mg dose of HHK001 (Leuprorelin Acetate Microspheres for Injection, an improved formulation) versus Enantone (Leuprorelin Acetate Microspheres for Injection) in patients with endometriosis. Approximately 20 patients will be enrolled and randomized in a 1:1 ratio to receive a single subcutaneous injection of HHK001 or Enantone. The post-dose blood sampling/follow-up period is 6 weeks for the Enantone group and 10 weeks for the HHK001 group.

Conditions

Endometriosis

Keywords

HHK001; Enantone; Leuprorelin Acetate; GnRH Agonist; Pharmacokinetics; Pharmacodynamics; Endometriosis

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax) of Leuprorelin

  Cmax of leuprorelin in plasma, determined by non-compartmental analysis of concentration-time data.

  Pre-dose on Day 1 and post-dose sampling: Day 1 (dense sampling), Days 2, 3, 5, 8, 11, 14, 21, 25, 29, 35, and 42 (both groups); additional sampling on Days 49, 57, 63, and 70 (HHK001 group only)

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of Leuprorelin

  AUC0-t of leuprorelin in plasma, determined by non-compartmental analysis of concentration-time data.

  Pre-dose on Day 1 and post-dose sampling: Day 1 (dense sampling), Days 2, 3, 5, 8, 11, 14, 21, 25, 29, 35, and 42 (both groups); additional sampling on Days 49, 57, 63, and 70 (HHK001 group only)

• Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Leuprorelin

  AUC0-inf of leuprorelin in plasma, determined by non-compartmental analysis of concentration-time data.

  Pre-dose on Day 1 and post-dose sampling: Day 1 (dense sampling), Days 2, 3, 5, 8, 11, 14, 21, 25, 29, 35, and 42 (both groups); additional sampling on Days 49, 57, 63, and 70 (HHK001 group only)

Secondary Outcomes (31)

• Time to Maximum Plasma Concentration (Tmax) of Leuprorelin

  Pre-dose on Day 1 and post-dose sampling: Day 1 (dense sampling), Days 2, 3, 5, 8, 11, 14, 21, 25, 29, 35, and 42 (both groups); additional sampling on Days 49, 57, 63, and 70 (HHK001 group only)

• Elimination Half-Life (t1/2) of Leuprorelin

  Pre-dose on Day 1 and post-dose sampling: Day 1 (dense sampling), Days 2, 3, 5, 8, 11, 14, 21, 25, 29, 35, and 42 (both groups); additional sampling on Days 49, 57, 63, and 70 (HHK001 group only)

• Apparent Clearance (CL/F) of Leuprorelin

  Pre-dose on Day 1 and post-dose sampling: Day 1 (dense sampling), Days 2, 3, 5, 8, 11, 14, 21, 25, 29, 35, and 42 (both groups); additional sampling on Days 49, 57, 63, and 70 (HHK001 group only)

• Apparent Volume of Distribution (Vd/F) of Leuprorelin

  Pre-dose on Day 1 and post-dose sampling: Day 1 (dense sampling), Days 2, 3, 5, 8, 11, 14, 21, 25, 29, 35, and 42 (both groups); additional sampling on Days 49, 57, 63, and 70 (HHK001 group only)

• Area Under the Curve From Time Zero to 7 Days (AUC0-7d) of Leuprorelin

  Pre-dose on Day 1 and post-dose sampling: Day 1 (dense sampling), Days 2, 3, 5, 8, 11, 14, 21, 25, 29, 35, and 42 (both groups); additional sampling on Days 49, 57, 63, and 70 (HHK001 group only)

Study Arms (2)

HHK001

EXPERIMENTAL

Participants receive a single subcutaneous injection of HHK001 (Leuprorelin Acetate Microspheres for Injection) 3.75 mg at the lower edge of the deltoid muscle of the upper arm on Day 1 to Day 5 of the menstrual period. Post-dose blood sampling and follow-up last 10 weeks (through Day 70). Approximately 10 participants.

Drug: HHK001 (Leuprorelin Acetate Microspheres for Injection)

Enantone

ACTIVE COMPARATOR

Participants receive a single subcutaneous injection of Enantone (Leuprorelin Acetate Microspheres for Injection) 3.75 mg at the lower edge of the deltoid muscle of the upper arm on Day 1 to Day 5 of the menstrual period. Post-dose blood sampling and follow-up last 6 weeks (through Day 42). Approximately 10 participants.

Drug: Enantone (Leuprorelin Acetate Microspheres for Injection)

Interventions

HHK001 (Leuprorelin Acetate Microspheres for Injection) DRUG

HHK001 is an improved formulation of Enantone; both are leuprorelin acetate microspheres for injection, a gonadotropin-releasing hormone (GnRH) agonist. A single dose of 3.75 mg is administered by subcutaneous injection at the lower edge of the deltoid muscle of the upper arm.

Also known as: HHK001

HHK001

Enantone (Leuprorelin Acetate Microspheres for Injection) DRUG

Enantone is leuprorelin acetate microspheres for injection, a gonadotropin-releasing hormone (GnRH) agonist, used as the active comparator. A single dose of 3.75 mg is administered by subcutaneous injection at the lower edge of the deltoid muscle of the upper arm.

Also known as: Enantone, Leuprorelin

Enantone

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntarily sign the informed consent form;
• Female, aged 18-45 years, body weight \>= 40 kg, body mass index 19-28 kg/m2;
• The most recent menstrual cycle before screening is 21-35 days;
• Diagnosed with endometriosis (previously diagnosed by histopathology, or confirmed by ultrasound or magnetic resonance imaging during screening); participants with concomitant adenomyosis or uterine fibroids are eligible; and assessed by the investigator as suitable for GnRH agonist therapy (no other therapeutic interventions allowed from the start of screening \[except rescue medication\]);
• Cervical cytology (TCT/LCT) result shows no intraepithelial lesion or malignancy (NILM) \[results from this study center within 1 year before screening are acceptable\];
• No plans for childbearing, oocyte cryopreservation, or oocyte donation from the start of screening until 3 months after dosing, and agreement to use effective contraception (complete abstinence, barrier methods, or non-medicated intrauterine device; no contraceptive medications allowed).

You may not qualify if:

• Allergy to GnRH agonists/antagonists (e.g., leuprorelin, triptorelin, goserelin, cetrorelix, ganirelix, degarelix), or a history of allergy to \>= 3 substances, or currently in an allergic state;
• Contraindications to the rescue medication (ibuprofen) (e.g., allergy to non-steroidal anti-inflammatory drugs, active peptic ulcer, or other conditions assessed by the investigator as contraindications);
• Current or previous osteoporosis/osteopenia, pituitary tumor, epilepsy, depressive disorder, thromboembolic events (e.g., myocardial infarction, cerebral infarction, deep vein thrombosis, pulmonary embolism), malignant tumors, abnormal uterine bleeding of unknown nature, or other conditions assessed by the investigator as unsuitable for this trial (e.g., diseases with acute/chronic pain, coagulation disorders, mental disorders, and various severe or unstable diseases);
• Receipt of GnRH agonists/antagonists (including investigational products in clinical trials) within 12 weeks before screening or during screening;
• Receipt of medications that may significantly affect hypothalamic-pituitary-gonadal axis hormone levels within 4 weeks before screening or during screening, such as estrogens/progestins/androgens and their derivatives/receptor modulators, aromatase inhibitors, etc.;
• Receipt of traditional Chinese medicine for endometriosis within 4 weeks before screening or during screening;
• Last treatment with an investigational product (drug or device) in a previous clinical trial \<= 4 weeks before screening (or \<= 12 weeks or 5 half-lives for therapeutic biological products, whichever is longer), or not yet withdrawn from another interventional clinical trial before enrollment;
• Previous surgery of the hypothalamus or pituitary gland;
• Any surgery within 4 weeks before screening or during screening (except endometriosis-related surgery), or planned surgery or invasive procedures after enrollment;
• History of miscarriage within 4 weeks before screening or during screening;
• Screening examination results meeting any of the following: systolic blood pressure \>= 160 mmHg, diastolic blood pressure \>= 100 mmHg, platelet count \<= 90 x 10\^9/L, hemoglobin \<= 80 g/L, alanine aminotransferase \>= 2 x ULN, aspartate aminotransferase \>= 2 x ULN, total bilirubin \>= 1.5 x ULN, serum creatinine \>= 1.5 x ULN, glycated hemoglobin (HbA1c) \>= 8.0%, Z-score \<= -2.0 at any site on dual-energy X-ray absorptiometry, hepatitis B surface antigen positive with HBV DNA \> ULN, hepatitis C virus antibody positive, human immunodeficiency virus antibody positive, or positive syphilis serology;
• Abnormal skin at the proposed injection sites (left and right upper arms) that affects dosing or assessment of injection site reactions (e.g., skin lesions, rashes);
• Acute blood loss or blood donation \>= 400 mL within 4 weeks before screening or during screening, or planned blood donation after enrollment;
• History of blood phobia, needle phobia, or difficult venous blood collection;
• History of alcohol dependence, drug abuse, or drug addiction;

Sponsors & Collaborators

• The Third Xiangya Hospital of Central South University: lead
• Zhuhai Huahaikang Pharmaceutical Technology Co., Ltd.: collaborator

MeSH Terms

Conditions

Endometriosis

Interventions

Injections; Leuprolide

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

Huang Jie

CONTACT

+86 731 8991 8665; cellahuang1988@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Pharmacology

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 28, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 28, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share