Progesterone for Infertility

(PROGRESS Trial)

Recruiting at 22 trial locations

Overseen By R&D Scientific Affairs

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: IBSA Institut Biochimique SA

Must not be taking: Insulin sensitizers, Vaginal medications

Disqualifiers: Diabetes, Endometriosis, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 10 weeks

680 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new injectable solution, Progesterone-IBSA, to assist with embryo implantation and early pregnancy in women facing infertility. It compares this treatment to an existing one, Crinone 8% (a progesterone vaginal gel), to determine if it performs equally well or better. The trial focuses on women who struggle to conceive despite having a healthy embryo ready for transfer. Ideal candidates are women aged 35 to 42 with a history of infertility and no more than two unsuccessful embryo transfers with healthy embryos. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for infertility.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications that might interfere with the study, such as insulin sensitizing agents, vaginal medications, and any hormonal treatments other than those specified in the protocol. If you are taking any of these, you may need to stop them before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that Progesterone-IBSA is generally safe for use in fertility treatments. Non-serious side effects occurred in about 42.6% of patients using Progesterone-IBSA, compared to 45.64% of those using Crinone, indicating similar safety levels for both treatments. Most side effects were not serious.

Research has shown that Crinone is safe and well-tolerated when used alone. Drug-related side effects occurred in about 14.4% of cases, including minor issues like vaginal discomfort.

Both treatments support pregnancy after embryo transfer. Studies suggest they are safe options with similar rates of mild side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Progesterone-IBSA Injectable Solution for infertility because it offers a novel delivery method. While most current treatments involve progesterone delivered intravaginally, Progesterone-IBSA is administered via subcutaneous injection, which could provide more consistent hormone levels. This method might enhance comfort and convenience for patients who find daily vaginal applications cumbersome. This new approach has the potential to improve the overall effectiveness and user experience compared to traditional options like Crinone.

What evidence suggests that this trial's treatments could be effective for infertility?

Research has shown that Progesterone-IBSA, a new injectable form of progesterone, effectively supports embryo implantation and early pregnancy. One study found it to be well-tolerated and as effective as traditional progesterone forms, such as Crinone. In this trial, participants in the investigational arm will receive Progesterone-IBSA, while Crinone, a vaginal gel used for the same purpose, is being studied in the comparator arm. Some studies have reported mixed results for Crinone, with some suggesting it might lower implantation rates, while others show similar pregnancy rates compared to other forms. In summary, both treatments in this trial are expected to support early pregnancy stages after embryo transfer, with Progesterone-IBSA showing promising results. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for premenopausal women aged 35-42 with a history of infertility, who have at least one euploid frozen blastocyst and less than three previous failed transfers. They must have normal menstrual cycles, not be breastfeeding or pregnant, and meet specific hormone levels. Exclusions include severe endometriosis, recurrent pregnancy loss, diabetes, liver/renal impairment, high grade cervical dysplasia, certain medication use within the last month.

Inclusion Criteria

I am seeking IVF due to infertility, being single, or in a same-sex relationship.

Subject has given written informed consent

Your body mass index (BMI) is less than 38 kg/m2.

Exclusion Criteria

I have a medical condition that prevents me from becoming pregnant.

I have a fibroid larger than 4 cm that changes the shape of my uterus or one that is over 5 cm.

My kidneys are not working well (low creatinine clearance).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active Progesterone-IBSA or Crinone 8% for luteal and early pregnancy support

10 weeks

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Long-term follow-up

Monitoring of delivery outcomes and adverse events related to the mother and newborn

2-4 weeks post expected delivery date

What Are the Treatments Tested in This Trial?

Interventions

• Progesterone-IBSA Injectable Solution
• Progesterone Vaginal Gel with Applicator

Trial Overview The study compares two forms of progesterone support for implantation after frozen embryo transfer: Progesterone-IBSA Injectable Solution versus Crinone Vaginal Gel. It's a multicenter trial where participants are randomly assigned to either treatment to assess which is more effective in supporting early pregnancy.

How Is the Trial Designed?

Group I: Investigational Experimental Treatment 2 Interventions

Progesterone-IBSA 25mg, twice daily (BID) subcutaneous (SC) injection every 12 hours and Crinone Placebo, once daily (QD) intravaginally.

Group II: Comparator Active Control 2 Interventions

Crinone 8%, 90 mg, QD intravaginally and Progesterone-IBSA Placebo, BID SC Injection every 12 hours

Progesterone-IBSA Injectable Solution is already approved in European Union, United States, Canada, Switzerland for the following indications:

Approved in European Union as Progesterone-IBSA for:

• Infertility
• Luteal phase support

Approved in United States as Progesterone-IBSA for:

• Investigational for luteal phase support and early pregnancy support

Approved in United States as Progesterone for:

• Contraception
• Control of abnormal uterine bleeding
• Maintenance of pregnancy
• Prevention of endometrial hyperplasia

Approved in Canada as Progesterone for:

• Contraception
• Control of abnormal uterine bleeding
• Maintenance of pregnancy
• Prevention of endometrial hyperplasia

Approved in Switzerland as Progesterone for:

• Contraception
• Control of abnormal uterine bleeding
• Maintenance of pregnancy
• Prevention of endometrial hyperplasia

Who Is Running the Clinical Trial?

IBSA Institut Biochimique SA

Lead Sponsor

Trials

42

Recruited

10,300+

Published Research Related to This Trial

A qualitative study involving 19 women undergoing Assisted Reproductive Technology (ART) treatments found that many preferred subcutaneous progesterone injections due to the convenience of once-daily administration and no vaginal discharge.

Despite the positive feedback on subcutaneous administration, some women still preferred vaginal progesterone due to concerns about self-injection and the inconvenience of carrying the medication, highlighting the importance of involving patients in the decision-making process regarding treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient attitudes towards and satisfaction with subcutaneous injection of progesterone versus vaginal administration in assisted reproductive technology treatment. Buhl Borgstrøm, M., Willum Adrian, S., Nøhr, B., et al.[2023]

In a study of 132 infertile patients undergoing IVF, both vaginal progesterone suppositories (Cyclogest) and tablets (Endometrin) showed no significant difference in perineal irritation after 14 days of use for luteal phase support.

However, more patients reported difficulty in administering Endometrin tablets compared to Cyclogest, indicating a potential convenience issue with the tablet form.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized comparison of side effects and patient convenience between Cyclogest suppositories and Endometrin tablets used for luteal phase support in IVF treatment. Ng, EH., Chan, CC., Tang, OS., et al.[2022]

In a study of 60 infertile patients, both Cyclogest vaginal suppositories and Crinone 8% vaginal gel were found to cause similar levels of perineal irritation, with about 20% of patients reporting this side effect.

However, significantly more patients using Cyclogest reported moderate to severe inconvenience related to administration, leaking, and interference with sexual activity, suggesting that Crinone gel may be a more user-friendly option for luteal support in IVF cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised comparison of side effects and patient inconvenience of two vaginal progesterone formulations used for luteal support in in vitro fertilisation cycles. Ng, EH., Miao, B., Cheung, W., et al.[2022]

In a study of 65 IVF patients, aqueous subcutaneous progesterone (Prolutex) showed comparable efficacy to vaginal progesterone (Crinone) for luteal support, with clinical pregnancy rates of 25.0% for Prolutex and 33.3% for Crinone, indicating no significant difference.

While Prolutex was associated with more local injection site pain, it resulted in less vaginal discharge and vulvar discomfort, suggesting it may be a preferable option for some patients seeking different administration routes for progesterone during IVF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of aqueous subcutaneous progesterone compared with vaginal progesterone as luteal support in in vitro fertilization: A randomized controlled study in Taiwan. Kao, TC., Tu, YA., Yang, PK., et al.[2022]

In a meta-analysis of two phase III trials involving 1435 IVF patients, subcutaneous progesterone did not show any significant difference in ongoing pregnancy rates or live birth rates compared to vaginal progesterone.

Both methods of progesterone administration had similar safety profiles, with no significant differences in the risk of ovarian hyperstimulation syndrome (OHSS), indicating that subcutaneous progesterone is a viable alternative for luteal phase support in IVF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials. Doblinger, J., Cometti, B., Trevisan, S., et al.[2022]

A new subcutaneous progesterone preparation offers the precise dosage of intramuscular injections while providing a more comfortable self-administration option, addressing the pain and complications associated with traditional methods.

The review discusses the pharmacokinetic and pharmacodynamic properties of this new formulation, supported by clinical evidence from two multicenter randomized trials, highlighting its potential for effective luteal support in infertility treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical and clinical development of a novel progesterone formulation. Cometti, B.[2015]

In a study involving 683 assisted reproduction technology patients, subcutaneous progesterone (Prolutex) demonstrated noninferiority to vaginal progesterone gel (Crinone) in ongoing pregnancy rates, with rates of 27.4% for Prolutex and 30.5% for Crinone, indicating both treatments are similarly effective for luteal phase support.

Both Prolutex and Crinone showed equivalent delivery and live birth rates, and the safety profiles were comparable, suggesting that Prolutex is a safe and well-tolerated alternative to Crinone for supporting pregnancies in ART patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous progesterone versus vaginal progesterone gel for luteal phase support in in vitro fertilization: a noninferiority randomized controlled study. Lockwood, G., Griesinger, G., Cometti, B.[2022]

Progesterone is crucial for supporting the luteal phase in assisted reproductive technologies like in-vitro fertilization and intrauterine insemination, highlighting its importance in fertility treatments.

While progesterone is commonly used to manage early pregnancy issues such as threatened abortion and recurrent miscarriage, the evidence for its effectiveness in these situations is not consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of progesterone in infertility and assisted reproduction. Ciampaglia, W., Cognigni, GE.[2015]

Progesterone and synthetic progestogens are crucial for maintaining pregnancy and are commonly prescribed to prevent issues like spontaneous preterm birth and pregnancy loss, especially in patients with recurrent pregnancy loss or threatened abortion.

The review highlights the various clinical scenarios where progestogens are used, including support during nonobstetric surgeries in pregnant women and as luteal support in infertility treatments, indicating their broad application in reproductive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of progestogens in pregnant and infertile patients. Ozlü, T., Güngör, AC., Dönmez, ME., et al.[2012]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11575947/

Clinical efficacy of Crinone on pregnancy outcomes in ... Our study shows that Crinone has no effect on biochemical and clinical pregnancies, but slightly reduces the rate of spontaneous abortions, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0015028299003647

Crinone 8% vaginal progesterone gel results in lower ... The use of Crinone 8% vaginal progesterone gel was associated with a lower implantation rate (16.6% versus 26.2%; odds ratio [OR] = 0.56; 95% confidence ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01959464?term=PROGESTERONE&aggFilters=results:with&viewType=Table&rank=3

NCT01959464 | Sexual Absorption of Vaginal Progesterone The secondary outcome variable will be the change in serum progesterone levels after coitus in the male partner comparing vaginal progesterone gel and placebo.

4. fertstert.org fertstert.org/article/S0015-0282(11)02794-4/abstract

Vaginal (Crinone 8%) gel vs. intramuscular progesterone ... Overall, patients who received vaginal P had higher pregnancy (70.9% vs. 64.2%) and delivery (51.7% vs. 45.4%) rates than did patients who received IMP.

5. academic.oup.com academic.oup.com/humrep/article/15/6/1284/2915562

Experience with progesterone gel for luteal support in a highly ... Based upon our findings, it is reasonable to conclude that luteal support from the vaginal progesterone gel appears to be as effective as i.m. progesterone, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32074281/

Efficacy, safety and tolerability of progesterone vaginal ... Drug-related AEs occurred with frequencies of 15.1% with progesterone vaginal pessaries and 14.4% with progesterone vaginal gel. Limitations, ...

7. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.16325?af=R

Multicenter cohort study of the effect of Crinone ... Conclusions. Use of Crinone progesterone vaginal gel alone is adequate in HRC-FBT and is not associated with any safety issues.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1472648318300555

Systematic review of the clinical efficacy of vaginal ... The aim was to compare the efficacy and safety of vaginal gel progesterone preparations (Crinone) with any other form of vaginal progesterone specifically for ...

9. fertstert.org fertstert.org/article/S0015-0282(02)04166-3/fulltext

The safety and efficacy of vaginal micronized progesterone ... Adverse events reported associated with vaginal administration of progesterone were leukorrea 0.8% and vaginal discomfort 0.4%. Conclusions: Single agent ...

10. journals.lww.com journals.lww.com/md-journal/fulltext/2024/11150/clinical_efficacy_of_crinone_on_pregnancy_outcomes.22.aspx

Clinical efficacy of Crinone on pregnancy outcomes in frozen This study demonstrated that the Crinone could protect women against spontaneous abortion, especially in patients who do not need HMG or in combination with ...