Testosterone Replacement for Hypogonadism

Recruiting at 17 trial locations

Overseen By Chief Medical Officer, MD, PhD

Age: < 18

Sex: Male

Trial Phase: Phase 3

Sponsor: Halozyme Therapeutics

Must be taking: Testosterone

Must not be taking: Antipsychotics, SSRIs, Glucocorticoids, others

Disqualifiers: Thyroid dysfunction, Hypertension, Tumors, 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

Compensation: Varies

Number of Visits: 4

Duration: 52 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of XYOSTED, a testosterone replacement therapy, on young males with hypogonadism, a condition where the body produces insufficient testosterone. The research focuses on the treatment's effectiveness in initiating or continuing puberty, as well as its safety and optimal dosage. Adolescent males aged 12 to under 18 with a known cause of low testosterone who require ongoing treatment to support puberty may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude participants who are currently taking certain medications like antipsychotics, SSRIs, and some others. It's best to discuss your specific medications with the study team to see if they might affect your eligibility.

Is there any evidence suggesting that XYOSTED is likely to be safe for humans?

Research has shown that XYOSTED, a treatment for low testosterone, has been tested for safety in people with hypogonadism. Some studies found that 25.6% of patients experienced side effects. The most common side effect was thicker blood, occurring in about 10% of patients. Serious issues, such as depression and even suicide attempts, were also reported during the research.

The FDA has approved XYOSTED for treating low testosterone in adults, indicating some proven safety. However, testosterone therapy can sometimes affect fertility, and this effect might be permanent. Prospective trial participants should discuss these possible side effects with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypogonadism?

Researchers are excited about XYOSTED for treating hypogonadism because it offers a unique delivery method compared to current options. Unlike traditional testosterone therapies that often require frequent intramuscular injections, XYOSTED is administered subcutaneously, which can be less painful and more convenient for patients. Additionally, XYOSTED provides a controlled release of testosterone enanthate, potentially improving hormone stability and reducing fluctuations in testosterone levels. These features may enhance patient compliance and overall treatment effectiveness.

What evidence suggests that XYOSTED might be an effective treatment for hypogonadism?

Research shows that XYOSTED, a testosterone injection, effectively treats adult men with low testosterone levels. Studies have found that testosterone treatments can initiate or sustain puberty in males with hypogonadism, a condition where the body produces insufficient testosterone. One study demonstrated significant benefits from testosterone treatment within the first year. Additionally, testosterone levels in patients receiving these treatments often remained within a normal range. This evidence suggests that XYOSTED could assist teenage boys with hypogonadism by regulating testosterone levels and supporting puberty. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for male adolescents aged 12 to under 18 with hypogonadism, weighing at least 40 kg and having a BMI-for-age above the 5th percentile. They must have been on a stable dose of prior testosterone treatment for at least three months if applicable, be willing to use contraception or practice abstinence, and have legal consent to participate.

Inclusion Criteria

My parent or guardian has agreed for me to join the study.

I am willing to agree to participate in the study.

My child's legal guardian agrees to follow and comply with the study requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive XYOSTED injections with dose adjustments based on testosterone levels and Tanner Stage

52 weeks

Regular visits for dose adjustments approximately every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XYOSTED

Trial Overview

The study tests XYOSTED as a testosterone replacement therapy over one year. It will assess how well it works in starting or continuing puberty, its safety profile, proper dosing levels, and effects on testosterone blood levels in boys with primary or secondary hypogonadism.

How Is the Trial Designed?

Group I: Participants Experimental Treatment 1 Intervention

XYOSTED Injection (Testosterone enanthate) 50mg / 0.5 mL, 75 mg/0.5 mL, 100 mg/0.5 mL

Who Is Running the Clinical Trial?

Halozyme Therapeutics

Lead Sponsor

Trials

47

Recruited

3,400+

Published Research Related to This Trial

Testosterone gel 1% significantly increased serum testosterone levels in adolescent boys with primary hypogonadism due to Klinefelter syndrome or anorchia, achieving pubertal levels after 6 months of treatment.

The treatment was generally safe, with cough being the most common adverse event reported, affecting 8 out of 29 participants, while no significant changes were observed in other hormone levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open-label, observational study of testosterone gel (1%) in the treatment of adolescent boys with klinefelter syndrome or anorchia. Rogol, AD., Swerdloff, RS., Reiter, EO., et al.[2013]

Testosterone is crucial for male health, with deficiencies leading to serious issues like reduced bone density, changes in body composition, and negative effects on mood and sexual function; androgen replacement therapy has been shown to improve these conditions significantly.

While androgen replacement is clearly beneficial for men with overt hypogonadism, the benefits for those with milder deficiencies or elderly men are less certain, and there is no established biochemical threshold for when treatment should begin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone deficiency and replacement. Howell, S., Shalet, S.[2018]

Androgen replacement therapy using parenteral testosterone esters, like testosterone enanthate or cypionate, is the most effective and safe treatment for male hypogonadism, helping to maintain normal sexual characteristics and function.

For men with secondary hypogonadism who wish to preserve fertility, gonadotropin therapy (starting with hCG) can stimulate natural testosterone production and spermatogenesis, although it is more complex and expensive than testosterone replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy of male hypogonadism. Matsumoto, AM.[2013]

Testosterone levels naturally decline with age, leading to many men experiencing low testosterone levels, or hypogonadism, which can be treated effectively with testosterone replacement therapies.

Recent developments, such as the Testogel and long-acting testosterone undecanoate injections, have shown promising results in maintaining stable testosterone levels and improving symptoms of hypogonadism, with a good safety profile over extended periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone supplementation: what and how to give. Jockenhövel, F.[2013]

Testosterone replacement therapy (TRT) shows promise for treating hypogonadism in older men, but significant safety concerns remain unresolved due to a lack of large-scale randomized trials comparing untreated hypogonadism with long-term TRT use.

Meta-analyses have identified key adverse events associated with TRT, including polycythemia, increased prostate-related events, and a slight reduction in HDL cholesterol, but the overall safety and utility of TRT continue to be debated in the medical community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of health risks of low testosterone and testosterone administration. Jia, H., Sullivan, CT., McCoy, SC., et al.[2022]

Androgen replacement therapy for male hypogonadism has been shown to improve sexual function, mood, muscle mass, and bone density in most men, confirming its efficacy as a treatment.

The safety of androgen treatment, especially in older men, remains uncertain, highlighting the need for careful consideration of potential risks alongside the benefits of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in male hormone substitution therapy. Qoubaitary, A., Swerdloff, RS., Wang, C.[2019]

Testosterone replacement therapy (TRT) is beneficial for older men with frank hypogonadism, leading to increased muscle mass, strength, and improved sexual function, but its use in men with low testosterone without symptoms remains controversial.

While TRT has established risks such as polycythemia and potential cardiovascular issues, it does not increase the risk of prostate cancer, and recent meta-analysis suggests that intramuscular TRT may have a better cardiovascular risk profile compared to oral or transdermal options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injection of testosterone may be safer and more effective than transdermal administration for combating loss of muscle and bone in older men. Borst, SE., Yarrow, JF.[2023]

In a study involving 999 men with hypogonadism over 2-3 years, testosterone replacement therapy (TRT) did not show a statistically significant increase in cardiovascular (CV) events compared to untreated men, suggesting that TRT may be safe in terms of CV health.

The study found that age and a history of cardiovascular issues were more significant predictors of new CV events than TRT use, indicating that underlying health conditions play a larger role in cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME). Maggi, M., Wu, FC., Jones, TH., et al.[2017]

In a study involving 5246 men aged 45 to 80 with hypogonadism and cardiovascular risk, testosterone-replacement therapy was found to be noninferior to placebo regarding major adverse cardiac events, indicating it does not significantly increase cardiovascular risk.

However, the testosterone group experienced a higher incidence of certain side effects, including atrial fibrillation, acute kidney injury, and pulmonary embolism, suggesting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Safety of Testosterone-Replacement Therapy. Lincoff, AM., Bhasin, S., Flevaris, P., et al.[2023]

In a study of 165 men with secondary hypogonadism undergoing testosterone replacement therapy (TRT), there was no significant difference in the risk of myocardial infarction (MI), stroke (CVA), or all-cause mortality compared to a matched control group of 210 men not receiving TRT.

The findings suggest that TRT does not have a protective or harmful effect on cardiovascular events in hypogonadal men, indicating that TRT may be safe in this population regarding cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone replacement therapy and the risk of adverse cardiovascular outcomes and mortality. Pantalone, KM., George, J., Ji, X., et al.[2022]

Exogenous testosterone is an established treatment for hypogonadism, with various modified analogs developed to improve pharmacokinetics and delivery methods, including transdermal therapies and long-acting injectables.

Current trends indicate a shift towards transdermal therapies and long-acting injectables as preferred options for testosterone replacement, aiming for safer, more effective, and patient-friendly treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The latest options and future agents for treating male hypogonadism. Edelstein, D., Sivanandy, M., Shahani, S., et al.[2019]

Testosterone treatment for male hypogonadism is highly effective and has evolved significantly, with new transdermal gels and injectable formulations providing more stable and physiological testosterone levels compared to older methods.

Recent advancements, such as mucoadhesive buccal tablets and long-acting injectable testosterone undecanoate, offer patients more convenient options for treatment, potentially improving adherence and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone treatment comes of age: new options for hypogonadal men. Nieschlag, E.[2022]

In a study involving 200 men, including 47 untreated hypogonadal men and 78 men receiving testosterone therapy, it was found that testosterone treatment resulted in prostate volume and PSA levels similar to those of normal age-matched men.

The results suggest that testosterone therapy does not lead to significant prostate enlargement in hypogonadal men, indicating that concerns about prostate growth should not prevent these men from receiving testosterone substitution therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Behre, HM., Bohmeyer, J., Nieschlag, E.[2019]

In a study of 30 hypogonadal men using 40 mg/day transdermal testosterone gel, serum testosterone levels peaked significantly at 2 hours after application but dropped notably by 23 hours, indicating the need for careful monitoring of testosterone levels throughout the day.

The findings suggest that measuring testosterone levels at both peak and trough times can help optimize testosterone replacement therapy, ensuring levels remain within a normal physiological range and preventing excessively high levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring testosterone replacement therapy with transdermal gel: when and how? Sansone, A., Sansone, M., Selleri, R., et al.[2020]

The clinical practice guidelines provide a comprehensive approach for diagnosing and treating hypogonadism in adult males, emphasizing the importance of initial hormonal evaluations and various diagnostic tests to tailor treatment effectively.

Testosterone replacement therapy is recommended for men with primary testicular failure and those with gonadotropin deficiency, while options for preserving fertility in hypogonadotropic patients include gonadal stimulation therapies and assisted reproductive technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update. Petak, SM., Nankin, HR., Spark, RF., et al.[2022]

Citations

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Prescribing Testosterone | XYOSTED® Health Care Provider

XYOSTED® is a virtually pain-free testosterone replacement for adult males who have low or no testosterone due to certain medical conditions.

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52 Week Study of Safety, PK, & Efficacy of XYOSTED® for ...

The study aims to determine the effectiveness of XYOSTED measured by continuation or induction of puberty in addition to XYOSTED dosage, safety and testosterone ...

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accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2019/209863Orig1s000StatR.pdf

Statistical Review(s)

The one submitted study provides evidence demonstrating the efficacy of Xyosted (testosterone enanthate) injection for the treatment of adult ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3188848/

Onset of effects of testosterone treatment and time span ...

A study administering testosterone enanthate, 200 mg/2 weeks observed major effects to occur over the first 12 months of testosterone administration, thereafter ...

5.

academic.oup.com

academic.oup.com/jsm/article/16/11/1741/6980701

Safety of a New Subcutaneous Testosterone Enanthate Auto ...

T trough levels ranged from 300−650 ng/dL (10.4−22.5 nmol/L) in 82.4% and 83.2% of patients at weeks 12 and 26, respectively. Of the 965 ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2019/209863Orig1s000MedR.pdf

Clinical Review(s) - accessdata.fda.gov

2) Two cases of suicide attempt (including one completed suicide) and two cases of depression were reported in the Xyosted development program; ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4774360/

Efficacy and safety of testosterone replacement therapy in ...

The purpose of the present meta-analysis was to evaluate the efficacy and safety of testosterone replacement therapy in men with hypogonadism.

8.

xyosted.com

xyosted.com/hcp

Prescribing Testosterone | XYOSTED® Health Care Provider

Reduced fertility is observed in some men taking testosterone replacement therapy. The impact on fertility may be irreversible. Pediatric Use—Safety and ...