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Trial registered on ANZCTR


Registration number
ACTRN12619001593123
Ethics application status
Approved
Date submitted
27/09/2019
Date registered
19/11/2019
Date last updated
18/10/2023
Date data sharing statement initially provided
19/11/2019
Date results information initially provided
2/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
ELONVA FLARE PROTOCOL: a new approach for poor responders in superovulation for In Vitro Fertilisation (IVF).
Scientific title
ELONVA FLARE PROTOCOL: a new approach for poor responders in superovulation for IVF aiming to develop detailed pharmacokinetic (PK) and pharmacodynamic (PD) profiles for Elonva Flare cycles.
Secondary ID [1] 299271 0
None
Universal Trial Number (UTN)
N/A
Trial acronym
EFP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertility 314408 0
Condition category
Condition code
Reproductive Health and Childbirth 312742 312742 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will receive a single subcutaneous injection of 150 mcg corifollitropin alfa (Elonva).
The gonadotropin-releasing hormone (GnRH) agonist flare protocol will use a day two of menses start of self-administration of GnRH agonist medication; nafarelin (Synarel), 2 mg/mL, intranasal twice daily, followed by a day three administration of Elonva.
Participants in the GnRH antagonist arm will self-administer a subcutaneous injection of Elonva on day two of menses and Orgalutran 250mcg, once daily from day 5 of Elonva.

All participants will receive daily recombinant follicle stimulating hormone (FSH) medication (Puregon), subcutaneously, 250 IU from day 7 of Elonva.
All participants will receive a single “trigger” injection of recombinant human chorionic gonadotropin (hCG) Ovidrel 250mcg, subcutaneosly when trigger criteria are met.
In the unlikely eventuality of an excessive ovarian response is observed, those in the antagonist arm will receive leuprolide acetate (Lucrin) trigger, 2mg/0.4mls subcutaneously or the cycle will be cancelled.
Those in the agonist flare arm will receive a half dose of Ovidrel, 125 mcg subcutaneously or the cycle will be cancelled.
All participants will use vaginal progesterone, 200 mg twice daily for luteal support until pregnancy test.

Duration of each drug may vary based on each participants' individual response to the fertility medications. Length of stimulation is approximately between 8-12 days.

Each participants will receive close monitoring throughout the stimulation phase with blood tests and transvaginal pelvic ultrasounds. The fertility clinic nurses and research nurse will be in regular contact with each participant throughout the trial to monitor adherence.
Intervention code [1] 315858 0
Treatment: Drugs
Comparator / control treatment
Ten women will be treated with an Elonva flare cycle and ten women with be treated with an Elonva antagonist cycle (control group). Each participant will be asked to provide a daily peripheral blood sample from initiation of corifollitropin alfa for 5 days, then alternate days till day of trigger or until day of cancellation.
Control group
Active

Outcomes
Primary outcome [1] 321378 0
Pharmacokinetics profile (AUC and T1/2) for Elonva Flare Protocol cycles assessed by serum analysis,
Timepoint [1] 321378 0
Daily from initiation of corifollitropin alfa for 5 days then alternate days for up to 12 days post-enrolment.
Primary outcome [2] 321917 0
Effect of corrifollitropin alfa compered with daily recombinant FSH on circulating concentration of estradiol
Timepoint [2] 321917 0
Concentration at final blood test before hCG trigger
Primary outcome [3] 321973 0
Effect of corrifollitropin alfa compered with daily recombinant FSH on circulating concentration of FSH
Timepoint [3] 321973 0
Concentration at final blood test before hCG trigger
Secondary outcome [1] 374822 0
Proportion of live births each arm of the study
Timepoint [1] 374822 0
This secondary timepoint will be up to 9 months following the last recorded pregnancy.
Secondary outcome [2] 376708 0
Number of oocytes obtained after use of corrifollitropin compared with daily recombinant FSH
Timepoint [2] 376708 0
Day of oocyte collection

Eligibility
Key inclusion criteria
- Female patients who are defined as a poor responder, according to the Poseidon criteria. (Poseidon Group 2 -Subgroup 2a only, Poseidon Group 3 & Poseidon Group 4)
- Female aged between 21- 42 years
- BMI 18.0-35.0
- Requiring IVF or Intracytoplasmic Sperm Injection (ICSI) and planned fertilisation of oocytes and fresh embryo transfer
Minimum age
21 Years
Maximum age
42 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Egg freeze cycle
- Severe male factor defined as <1 million/mL
- Previous cancer treatment or any other exogenous factor affecting ovarian function
- PCO or PCOS according to Rotterdam criteria
- Patients with a significant pre-existing physical or mental health condition.
- Unable to fully give informed consent to participate

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)
Online randomisation through the secure platform called RedCAP.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Algorithm created by the UNSW Stats Central staff.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Fertility patients identifyed as poor responders, will be randomly allocated either two medication regimes, Elonva Flare or Elonva Antagonist.
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
This is an intense PK study, Ten women in each arm will allow for comparison of PK and PD profiles using non parametric statistics.
Sample size of twenty patients was chosen as this is a proof of concept study. No sample size calculations were performed as this is not required for this phase of the trial.
Should the results of this study be in favour of the EFP, then we will undertake a multicentre RCT to compare EFP with CFA with oocyte number as the primary outcome, using the data from the initial study to support a power calculation.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2020
Actual
5/05/2021
Date of last participant enrolment
Anticipated
1/04/2022
Actual
30/04/2023
Date of last data collection
Anticipated
31/10/2022
Actual
31/08/2023
Sample size
Target
20
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25658 0
Royal Hospital for Women - Randwick
Recruitment postcode(s) [1] 41482 0
2000 - The Rocks
Recruitment postcode(s) [2] 41481 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 303805 0
Commercial sector/Industry
Name [1] 303805 0
Merck, Sharp and Dohme
Country [1] 303805 0
Australia
Primary sponsor type
University
Name
UNSW
Address
UNSW Sydney
High St Kensington
NSW 2052 Australia
Country
Australia
Secondary sponsor category [1] 303928 0
None
Name [1] 303928 0
Address [1] 303928 0
Country [1] 303928 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304322 0
South Eastern Sydney Local Health District (SESLHD)
Ethics committee address [1] 304322 0
SESLHD HREC
District Executive Unit, Level 4
The Sutherland Hospital & Community Health Service
Cnr The Kingsway and Kareena Road
CARINGBAH NSW 2229
Ethics committee country [1] 304322 0
Australia
Date submitted for ethics approval [1] 304322 0
08/02/2021
Approval date [1] 304322 0
03/05/2021
Ethics approval number [1] 304322 0
2020/ETH03168

Summary
Brief summary
There is an unmet need for an effective way to treat poor responding patients to superovulation for IVF. We predict the Elonva Flare Protocol (EFP) may be an innovative way to treat fertility patients who are told their chances of conception are low.
We hypothesise that the unique PK/PD profile of Corifollitropin alfa (CFA) will maximise follicle stimulating hormone (FSH) exposure and follicular recruitment in the critical early follicular phase. Additionally, we hypothesise that the unique PK/PD properties of Elonva when combined with a short agonist flare cycle will maximise FSH exposure at the critical time of antral follicle recruitment, leading to a higher oocyte yield and improved pregnancy rate. EFP involves sufficiently fewer injections when compared with antagonists or long down regulated cycles. We predict that this will be attractive to patients, with less injection associated stress.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96534 0
Prof William Ledger
Address 96534 0
UNSW
School of Women's and Children's Health
Level 1, Royal Hospital for Women
Barker Street, RANDWICK NSW 2031
Country 96534 0
Australia
Phone 96534 0
+61 2 9382 6515
Fax 96534 0
Email 96534 0
w.ledger@unsw.edu.au
Contact person for public queries
Name 96535 0
Ms Prudence Sweeten
Address 96535 0
UNSW
School of Women's and Children's Health
Level 1, Royal Hospital for Women
Barker Street, RANDWICK NSW 2031
Country 96535 0
Australia
Phone 96535 0
+61 2 9382 6515
Fax 96535 0
Email 96535 0
p.sweeten@unsw.edu.au
Contact person for scientific queries
Name 96536 0
Dr Rachael Rodgers
Address 96536 0
UNSW
School of Women's and Children's Health
Level 1, Royal Hospital for Women
Barker Street, RANDWICK NSW 2031
Country 96536 0
Australia
Phone 96536 0
+61 2 9382 6515
Fax 96536 0
Email 96536 0
rachael.rodgers@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
4760Informed consent form  p.sweeten@unsw.edu.au


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 378369-(Uploaded-18-10-2023-16-12-39)-Basic results summary.pdf

Documents added automatically
No additional documents have been identified.