Progesterone for Infertility

(PROGRESS Trial)

Recruiting at 17 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

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority clinical study in women aged 35 to 42 years. This study will investigate the safety and efficacy of Progesterone-IBSA to support euploid embryo blastocyst implantation and early pregnancy after frozen embryo transfer (FET) in a modified natural cycle as a treatment for infertile women. Subjects will be randomized to receive either active Progesterone-IBSA or Crinone 8% for luteal and early pregnancy support and these two groups will be compared.

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.

What data supports the effectiveness of the drug Progesterone-IBSA Injectable Solution for infertility?

Research shows that subcutaneous progesterone, like Progesterone-IBSA, is effective and safe for supporting the luteal phase in IVF treatments, which is crucial for successful embryo implantation and pregnancy. ^{1 2 3 4 5}

Is progesterone safe for use in humans?

Research shows that progesterone, whether given as an injection or vaginally, is generally safe for use in supporting fertility treatments like IVF. Studies have compared different forms of progesterone and found them to be well-tolerated with manageable side effects. ^{1 2 3 5 6}

How is the drug Progesterone-IBSA Injectable Solution unique for treating infertility?

Progesterone-IBSA Injectable Solution is unique because it combines the precise dosage of an injectable form with the comfort of a subcutaneous (under the skin) self-administration, avoiding the pain and complications of intramuscular injections and the discomfort of vaginal applications. ^{1 4 7 8 9}

Eligibility Criteria

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

Subject has given written informed consent

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

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]

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]

References

1. China (Republic : 1949- ) 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. [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Subcutaneous progesterone versus vaginal progesterone gel for luteal phase support in in vitro fertilization: a noninferiority randomized controlled study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. Ireland 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. [2022]

6. Ireland 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. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Patient attitudes towards and satisfaction with subcutaneous injection of progesterone versus vaginal administration in assisted reproductive technology treatment. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Use of progestogens in pregnant and infertile patients. [2012]

9. United States pubmed.ncbi.nlm.nih.gov

Clinical use of progesterone in infertility and assisted reproduction. [2015]