ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12624001371583

Ethics application status

Approved

Date submitted

21/09/2024

Date registered

18/11/2024

Date last updated

18/11/2024

Date data sharing statement initially provided

18/11/2024

Type of registration

Retrospectively registered

Titles & IDs

Public title

A Phase 1 Safety and Pharmacokinetics Study of GB-hMG in Healthy Women

Scientific title

A Phase 1, Single Dose Study to Evaluate the Safety and Pharmacokinetics of GB-hMG (Menotropins) for Subcutaneous Injection in Healthy Premenopausal Women

Secondary ID [1]

GBHMG-101

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Infertility

Condition category

Condition code

Reproductive Health and Childbirth

Fertility including in vitro fertilisation

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This is a phase 1, open-label, randomised, single-centre study to evaluate the safety, immunogenicity, pharmacokinetics, and pharmacodynamics of a single administration of GB-hMG in healthy premenopausal females.

Thirty eligible, healthy volunteers will be randomised to one of four single doses and receive one (1) subcutaneous (SC) injection of 150 international units (IU), 225 IU, 300 IU, or 450 IU, to evaluate the pharmacokinetics and dose proportionality of GB-hMG.

The dose will be administered via SC injection into the abdomen by an appropriately qualified, Good Clinical Practice (GCP)-trained, and experienced member of the study staff.

Participants will remain under observation at the CRU for 2 days after administration of study drug and will be discharged only after review by the Investigator (i.e., Study Day 3).

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

GB-hMG Dose Comparison between 150IU, 225IU, 300IU and 450IU.

Control group

Dose comparison

Outcomes

Primary outcome [1]

To assess the safety and tolerability profile of a single subcutaneous administration of GB-hMG at 4 dose levels in healthy premenopausal women.

Assessment method [1]

(1) Frequency and severity of all AEs, like injection site reactions, pain, inflammation.
(2) Prior to the administration of study intervention on Day 1, the injection site should be cleaned with an antiseptic pad, prepped, and examined to assure that the areas are not inflamed, infected, swollen, painful, or otherwise abnormal. After SC administration of study intervention, the injection site will be inspected for dermal response.
(3) Blood pressure and pulse rate will be measured after the participant has rested in sitting position for at least 3 min in a quiet setting without distractions (e.g., television, cell phones) using an Omron automated blood pressure and pulse rate monitor. Manual techniques will be used only if an automated device is not available. The acceptable systolic and diastolic blood pressure ranges are defined as between 90 and 130 mmHg, and between 50 and 80 mmHg, respectively. The acceptable pule rate range is defined as between 45 bpm and 100 bpm. Tympanic body temperature will also be assessed. If tympanic measurement is not possible, oral can also be accepted, as long as measurement is always performed the same way for the respective participant. The acceptable body temperature range is defined as between 35.5 °C and 37.7 °C. Respiratory rate will also be assessed. The acceptable respiratory rate is defined as between 12 rpm and 22 rpm. Vital signs may be repeated at the discretion of the Investigator to confirm out of range results.
(4) A complete physical examination will be conducted at Screening and will include, at a minimum, HEENT (head, ears, eyes, nose, and throat examination), general appearance, neck (including thyroid and nodes), cardiovascular, respiratory, gastrointestinal, renal, neurological, musculoskeletal, skin and other.
(5) A 12-lead electrocardiogram (ECG) will be performed (and the results recorded in the eCRF) to verify that the cardiac status of the participant before involvement in the study is sufficient to meet protocol entry criteria. The ECG will be performed with the participant in a supine position for 5 - 10 min, and if not tolerated, a semi-supine position. Site standard reference ranges will apply for all ECG assessments.
(6) Blood samples should be drawn after other safety assessments (e.g., vital signs, physical examination, ECG) have been completed. The Investigator or delegate must review the laboratory results, document this review, and record any clinically significant changes occurring during the study as an AE, as determined based on the Investigator or medical delegate’s judgement.

Timepoint [1]

(1) All AEs and SAEs will be collected daily from informed consent until Day 14.
(2) The injection site will be checked at -1 hours pre-dose, 1, 2, 4, 6, 8, 12, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44 hours. Additional injection site assessments will be performed at 48, 72, 96, 120, 144, 192 hours, with a final injection site assessment performed on Day 14 at 312 hours.
(3) Vital Signs will be checked at Pre-dose (-1h), 1h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 192h, 312h.
(4) A complete physical examination at Screening and an abbreviated physical examination will be conducted on Day -1 (heart, lungs, abdomen, and skin). On all other study days where physical examination is required, a symptom-directed physical examination, under the discretion of the Investigator or delegate, will be performed.
(5) A 12-lead ECG at Screening, Day –1 (-24h) and Day 14 (312h).
(6) Pre-dose –1h, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 144, 192, 312 hours.

Secondary outcome [1]

To investigate the pharmacokinetic profile of GB-hMG

Timepoint [1]

Day 1 (treatment day) up until Day 9 (post dose). Blood samples collected at hours: -1, -0.5, -0.1, 1, 2, 4, 6, 8, 12, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, 72, 96, 120, 144, 192.

Secondary outcome [2]

To investigate the pharmacodynamic profile of GB-hMG

Timepoint [2]

Blood sample collected on post-dose Day 3 (72h)

Secondary outcome [3]

To assess immunogenicity of GB-hMG

Timepoint [3]

Blood sample collected on Day –1 (baseline screening, timepoint not defined as it can be any time before Study Drug administration) and Day 14 (312 h)

Eligibility

Key inclusion criteria

1. Healthy pre-menopausal female volunteers (18-42 years old) that will undergo pituitary suppression as part of the study. Healthy status will be determined by the Investigator based on medical history, gynaecological examinations, clinical laboratory results, vital signs, electrocardiogram measurements, and physical examination at Screening.
2. Participants willing and able to give personal signed informed consent and comply with all scheduled visits, drug administration plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Participants will have a Body Mass Index (BMI) of 18-38 kg/m2
4. Participants will have regular menstrual cycles of 24-35 days, as confirmed by participant and documented in the source documentation.
5. Participants will have a negative Cervical Screening Test or Pap Smear within 5 years if human papillomavirus (HPV) vaccinated or 3 years if not HPV vaccinated.
6. Participants will be taking an oral contraceptive pill (OCP) or be assessed as suitable and willing to take an OCP for a period of 2 weeks prior to receiving GnRH agonist.
7. Participants will have a Baseline transvaginal ultrasound (TVUS) showing no ovarian follicles/cysts greater than 11 mm after receiving OCPs (Day -11) and prior to check-in after conclusion of GnRH agonist treatment period (Day -1; window -3 days).
8. Participants will have Baseline (Day -1) serum FSH levels less than 4 IU/L, estradiol (E2) levels less than or equal to 50 pg/mL, and progesterone (P4) levels less than 1 ng/mL prior to receiving GB-hMG.
9. Participants who smoke no more than 2 cigarettes per day or equivalent per week (including e-cigarettes) can be included in the study. Note: Participants must discontinue smoking/use of nicotine-containing products from 48 hours before first study drug administration through Day 14.
10. Participants will not be lactating and must test negative for pregnancy prior to OCP and before and after receiving GnRH agonist.
11. Participants must use effective methods of contraception once they pass screening and agree to participate and at conclusion of the study as outlined below:

Prior to Screening and until Day -26 (use method A or B below):
A. Established use of oral hormonal methods of contraception, and
I. A barrier method (i.e., condom or diaphragm)
II. Male partner vasectomised at least 6 months prior to the Screening visit (the partner is the sole sexual partner of the woman of childbearing potential and the
vasectomised partner has received medical assessment of the surgical success
(verbal confirmation of male partner/s vasectomy is acceptable)
III. Abstinence
B. Non-hormonal intrauterine device (IUD)/ intrauterine system (IUS), and
I. A barrier method (i.e., condom or diaphragm)
II. Male partner vasectomised at least 6 months prior to the Screening visit (the partner is the sole sexual partner of the woman of childbearing potential and the
vasectomised partner has received medical assessment of the surgical success (verbal confirmation of male partner/s vasectomy is acceptable)
III. Abstinence

Pretreatment (OCP) Day -25 to Day -12
A. OCP, and
I. A barrier method (i.e., condom or diaphragm)
II. Male partner vasectomised at least 6 months prior to the Screening visit (the partner is the sole sexual partner of the woman of childbearing potential and the
vasectomised partner has received medical assessment of the surgical success (verbal confirmation of male partner/s vasectomy is acceptable)
III. Abstinence

On Study Day -11 to Day 14 (use methods A, B, C, or D below):
A. Non-hormonal IUD/IUS
B. Male partner vasectomised at least 6 months prior to the Screening visit (the partner is the sole sexual partner of the woman of childbearing potential and the vasectomised partner has received medical assessment of the surgical success (verbal confirmation of male partner/s vasectomy is acceptable)
C. Abstinence
D. A barrier method (i.e., condom or diaphragm)

Post EOS/Day 14:
From Day 14 until 28 days after receiving GB-hMG, the participant may return to using hormonal contraception including having an IUD/IUS inserted, depot injection per the following options (A or B):
A. OCP, and
I. A barrier method (i.e., condom or diaphragm)
II. Male partner vasectomised at least 6 months prior to the Screening visit (the partner is the sole sexual partner of the woman of childbearing potential and the
vasectomised partner has received medical assessment of the surgical success (verbal confirmation of male partner/s vasectomy is acceptable)
III. Abstinence
B. Non-hormonal or hormonal IUD/ IUS, and
I. A barrier method (i.e., condom or diaphragm)
II. Male partner vasectomised at least 6 months prior to the Screening visit (the partner is the sole sexual partner of the woman of childbearing potential and the vasectomised partner has received medical assessment of the surgical success (verbal confirmation of male partner/s vasectomy is acceptable)
III. Abstinence

Minimum age

18 Years

Maximum age

42 Years

Sex

Females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Any concomitant disease, condition, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the Investigator or Sponsor, pose an unacceptable risk to the participant in the study or interfere with the interpretation of study data. Particular attention should be given to history or evidence of clinically significant cardiovascular, pulmonary (except for resolved childhood asthma), hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, autoimmune diseases, dermatologic, neurologic, oncologic, and psychiatric disease (except for mild depression and anxiety).
2. History of (or current) endocrine abnormalities such as hyperprolactinaemia, polycystic ovary syndrome, and any evidence of ovarian dysfunction.
3. Positive alcohol breath test and/or urine drug test. The urine drug test will be considered positive if any of the following are detected in the urine: Methamphetamine, opiates,
cocaine, cannabis, phencyclidine, benzodiazepines, barbiturates, methadone, tricyclic antidepressants, and amphetamine.
4. Regular alcohol consumption defined as greater than 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL glass of wine). Participant is unwilling to abstain from alcohol beginning 48 hours prior to admission to the CRU through Day 14.
5. Uncontrolled hypertension or blood pressures defined as systolic blood pressure (BP) greater than 130 mmHg or less than 90 mmHg and/or diastolic BP greater than 80 mmHg or less than 50 mmHg. Blood pressure and heart rate will be measured in a sitting position following 5 minutes rest. Two repeats will be allowed at the discretion of the Investigator. Please note that BP well controlled with BP lowering agents is allowed at the discretion of the Investigator.
6. Use of medications that will interfere with OCP metabolism including antibiotics, anticonvulsants, antifungals, and herbal supplements (during OCP treatment phase).
7. Any contraindication or hypersensitivity to gonadotropin, GnRH agonist therapy, or OCPs or any formulation components thereof.
8. Any tattoos or scars that might impact assessment of incident severity rating, as judged by the Investigator.
9. Participant is pregnant or lactating or intending to become pregnant or donate ova before, during, or within 28 days after receiving GB-hMG.
10. Participants must have clinical laboratory values within normal ranges or less than 3 times upper limit of normal (ULN) as specified by the testing laboratory, unless deemed not clinically significant (NCS) by the Investigator. Repeat testing at Screening is acceptable once more if it is not less than two weeks or not more than two months afterward for out-of-range values following approval by the Investigator or delegate.
11. Impaired renal function as determined by the Investigator, based on an estimated eGFR less than 90 mL/min/1.73 m2 at Screening.
12. Has an established diagnosis of Type 1 or Type 2 diabetes mellitus, as indicated by use of diabetes medication, HbA1C greater than 6.4% or fasting glucose greater than or equal to 97.3 mg/dL (5.4 mmol/L).
13. Participants must test negative for hepatitis B surface antigen, hepatitis C antibodies, and HIV-1 and HIV-2 antibodies at Screening.
14. Active malignancy and/or history of malignancy in the past 5 years, with the exception of completely excised non-melanoma skin cancer or low grade cervical intraepithelial
neoplasia.
15. Participants must not have fever (body temperature greater than 37.7°C) within 2 days of receiving study intervention.
16. Participant has received any experimental drug within 30 days and/or 5 half-lives of the experimental drug, whichever is longer, prior to Screening. Participants who are off
treatment of the experimental drug and are on observation/long term follow up will be considered on a case-by-case basis.
17. Participant has donated or lost 470 mL or more of his or her blood volume (including plasmapheresis) or had a transfusion of any blood product within 12 weeks prior to
Screening

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Central randomisation via the interactive web response system (IWRS) module of the study database (Viedoc).

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Permuted block randomisation

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

25/10/2024

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Granata Bio Pty Ltd

Address [1]

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Accelagen Pty Ltd

Address

Country

Australia

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

Granata Bio Pty Ltd

Address [1]

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Human Research Ethics Committee D

Ethics committee address [1]

https://bellberry.com.au/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

28/08/2024

Approval date [1]

27/09/2024

Ethics approval number [1]

Summary

Brief summary

This is a phase 1, open-label, randomised, single-centre study to evaluate the safety, immunogenicity, pharmacokinetics, and pharmacodynamics of a single administration of GB-hMG in healthy premenopausal females. 

Thirty eligible, healthy volunteers will be randomised to one of four single doses and receive one (1) subcutaneous (SC) injection of 150 international units (IU), 225 IU, 300 IU, or 450 IU, to evaluate the pharmacokinetics and dose proportionality of GB-hMG.

GB-hMG contains follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotropin (hCG). FSH, hCG and LH are produced by your body as part of your regular hormonal cycles. It is thought that GB-hMG will be able to stimulate the ovaries to increase fertility and ability to produce healthy ova.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Jessica Gehlert

Address

CMAX Clinical Research Pty Ltd Ground Floor, 21-24 North Terrace Adelaide, South Australia 5000

Country

Australia

Phone

+61 0421 311 443

Fax

jessica.gehlert@cmax.com.au

Contact person for public queries

Name

Briohny Johnson

Address

CMAX Clinical Research Pty Ltd Ground Floor, 21-24 North Terrace Adelaide, South Australia 5000

Country

Australia

Phone

+61 8 7088 7900

Fax

Briohny.johnson@cmax.com.au

Contact person for scientific queries

Name

Jessica Gehlert

Address

CMAX Clinical Research Pty Ltd Ground Floor, 21-24 North Terrace Adelaide, South Australia 5000

Country

Australia

Phone

+61 0421 311 443

Fax

jessica.gehlert@cmax.com.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Privacy and intellectual property considerations

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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