Pegvisomant for Growth Hormone Excess

Overseen By Samah M Agabein, M.D.

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Must be taking: Somatostatin analogues, Dopamine agonists

Must not be taking: Opioids

Disqualifiers: Liver abnormalities, Pregnancy, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 60 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug pegvisomant can help children and teenagers with gigantism, a condition where excessive growth hormone causes abnormal growth and other health issues. The goal is to determine if pegvisomant, which blocks the effects of growth hormone, can serve as an effective treatment for those who have not found success with current methods. Participants should be aged 2 to 18 and have experienced unsuccessful results with standard treatments like surgery or radiation. 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.

Will I have to stop taking my current medications?

If you are taking medications for growth hormone excess, you can continue them as long as the dose is stable. If you want to stop those medications, you need a 6-week break before starting the trial.

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

Research has shown that pegvisomant is a safe treatment option. Studies involving patients with acromegaly, a condition similar to gigantism, have found it to be well-tolerated. Specifically, data from ACROSTUDY, which examined pegvisomant use in acromegaly patients, found it to be effective and safe over time. Another study with 251 patients in Japan supported these findings. These studies suggest that pegvisomant is generally safe for treating growth hormone issues. However, since researchers are still studying its use in children with gigantism, participating in a clinical trial is important to better understand its safety for this specific group. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for growth hormone excess, like somatostatin analogs and dopamine agonists, work by reducing the production of growth hormone. But pegvisomant works differently; it acts as a growth hormone receptor antagonist. This means that instead of stopping the production of growth hormone, it blocks the hormone's effects at its target sites in the body. Researchers are excited about pegvisomant because it offers a novel approach that directly targets and neutralizes excess growth hormone activity, potentially providing more effective symptom control for patients.

What evidence suggests that pegvisomant might be an effective treatment for growth hormone excess?

Research shows that pegvisomant effectively treats conditions with excess growth hormone, such as acromegaly. In studies involving individuals with acromegaly, pegvisomant has normalized levels of IGF-I, a key marker of growth hormone activity. Long-term evidence indicates that it is both safe and effective, making it a promising option for managing excess growth hormone. Pegvisomant blocks the action of growth hormone, helping to control abnormal growth. Although not specifically approved for gigantism, its success in treating similar conditions suggests potential benefits for those with growth hormone issues. Participants in this trial will receive pegvisomant to further evaluate its effectiveness. ^{4 6 7 8 9}

Who Is on the Research Team?

Karim A Calis, Pharm.D.

Principal Investigator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Are You a Good Fit for This Trial?

This trial is for children and teens aged 2-18 with growth hormone excess, typically causing abnormal growth (gigantism), who haven't had success with standard treatments or can't use them. They must be willing to stop other GH treatments before starting the study drug, agree to certain birth control methods if applicable, have a local doctor for regular check-ups, and not have liver issues or current opioid use.

Inclusion Criteria

I am willing to stop my current GH excess treatments for 6 weeks before starting pegvisomant.

I am between 2 and 17 years old.

Able to provide consent/assent if developmentally appropriate

Exclusion Criteria

Positive pregnancy test in females, current pregnancy and/or female patients who are breastfeeding

Patients with any medical, physical, psychiatric, or social condition, which, in the opinion of the investigators, would make participation in this protocol not in their best interest

My liver tests are three times above the normal range.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Participants undergo baseline assessments including medical history, physical exam, and initial drug administration

1 week

1 visit (in-person, overnight stay)

Treatment

Participants receive daily injections of pegvisomant and undergo regular monitoring including monthly local doctor visits for height, weight, and blood tests

60 weeks

3 main visits (baseline, 6-month, 12-month), monthly local visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pegvisomant

Trial Overview The trial tests Pegvisomant's safety and effectiveness in managing excessive growth hormone in kids. Over 60 weeks, participants will visit at least three times for medical exams, questionnaires, heart/liver tests, MRI scans with dye injection, hand X-rays and learn to self-inject the drug daily at home.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 1 Intervention

Intervention arm, Patient received pegvisomant

Pegvisomant is already approved in United States, European Union for the following indications:

Approved in United States as Somavert for:

• Acromegaly

Approved in European Union as Somavert for:

• Acromegaly

Who Is Running the Clinical Trial?

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Lead Sponsor

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Pegvisomant effectively normalizes serum IGF-I levels in 97% of patients with acromegaly, which is crucial for managing the disease's activity.

The drug is beneficial for patients who do not respond well to somatostatin analogs and may also be particularly advantageous for those with acromegaly and diabetes mellitus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of pituitary tumors: pegvisomant. Paisley, AN., Drake, WM.[2018]

Pegvisomant is an effective second-line treatment for acromegaly, specifically designed to block the action of growth hormone (GH) by targeting its receptor, and it can be used alone or with somatostatin analogues to manage elevated GH levels.

Preliminary studies suggest that pegvisomant may also improve insulin sensitivity in type 1 diabetes and could potentially play a role in cancer treatment and diagnosing GH deficiency, although these applications need further research to confirm their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegvisomant: current and potential novel therapeutic applications. Thankamony, GN., Dunger, DB., Acerini, CL.[2021]

In the German Pegvisomant Observational Study (GPOS) involving 263 patients with acromegaly, pegvisomant treatment led to normalization of disease activity in most patients and improved glucose metabolism, demonstrating its efficacy as a growth hormone-receptor antagonist.

The safety profile of pegvisomant was favorable, with tumor growth rates similar to those seen with somatostatin analogues, and while some patients experienced transaminase elevations, these were mostly transient and resolved without long-term issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience from the German pegvisomant observational study. Strasburger, CJ., Buchfelder, M., Droste, M., et al.[2016]

Pegvisomant is a growth hormone receptor antagonist that has shown to be highly effective in treating acromegaly, a condition caused by excess growth hormone.

Initial results indicate that pegvisomant is the most effective treatment for achieving biochemical control of the disease, as measured by levels of circulating IGF-I.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic effects of GH antagonism in patients with acromegaly. Trainer, PJ.[2019]

Pegvisomant, a pegylated form of the mutant growth hormone B2036, retains the ability to bind to growth hormone receptors but prevents proper signaling, making it an effective antagonist.

Despite having lower antagonistic activity than its unpegylated counterpart, pegvisomant's significantly reduced clearance rate allows it to be an effective treatment for conditions like acromegaly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegvisomant: structure and function. Pradhananga, S., Wilkinson, I., Ross, RJ.[2021]

Pegvisomant acts as a competitive antagonist to the growth hormone receptor, which may provide therapeutic benefits in conditions like acromegaly and potentially in cancer treatment.

Initial studies have shown pegvisomant's in vitro effectiveness against meningioma and in vivo effectiveness against colon and breast cancer cell lines, suggesting its potential as an antineoplastic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer and the potential place for growth hormone receptor antagonist therapy. Friend, KE.[2021]

Pegvisomant, a growth hormone receptor antagonist introduced in 2004, provides an effective treatment option for patients with acromegaly who do not respond adequately to surgery, radiation, or other medical therapies, demonstrating good tolerance and safety based on the Acrostudy database.

Clinical trials are underway to explore the combination of pegvisomant with somatostatin analogs, which may enhance treatment efficacy and expand the potential uses of growth hormone receptor antagonists beyond acromegaly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Growth hormone receptor antagonist in the treatment of acromegaly]. Hubina, E., Tóth, A., Kovács, GL., et al.[2016]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35022929/

Patient-reported outcomes in patients with acromegaly ... Overall, patients treated with PEGV had small improvements in PASQ. While IGF-I normalization increased with PEGV treatment, IGF-I control ...

2. somavert.pfizerpro.com somavert.pfizerpro.com/decades-of-results

Decades of Results Publication of data for 710 patients who received SOMAVERT ... Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1521690X24000642

Growth hormone receptor antagonist pegvisomant and its ... Sufficient longitudinal follow-up data suggest that it can be deemed both safe and effective. It is the drug with the greatest potential for achieving an ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27932529/

Effectiveness of first-line pegvisomant monotherapy in ... Objective: To examine the effectiveness and safety of primary pegvisomant monotherapy. Design: Retrospective analysis of data extracted from ACROSTUDY (global ...

5. academic.oup.com academic.oup.com/ejendo/article/185/4/525/6654392

More than a decade of real-world experience of pegvisomant ... This comprehensive review of the complete cohort in ACROSTUDY confirmed the overall favourable benefit-to-risk profile and high efficacy of PEGV as mono- and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22362824/

Long-term safety of pegvisomant in patients with acromegaly Data entered and evaluated in ACROSTUDY indicate that pegvisomant is an effective and safe medical treatment in patients with acromegaly.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31723069/

Long-term safety and treatment outcomes of pegvisomant ... Data for 251 patients with acromegaly treated with pegvisomant were collected from 119 institutions nationwide in Japan. Eighty-five patients ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03882034

Safety and Efficacy of Pegvisomant in Children With ... The objectives of the proposed study are to characterize the efficacy of pegvisomant as indicated by adequate control of the IGF-1 levels.

9. somavert.pfizerpro.com somavert.pfizerpro.com/efficacy-safety/acrostudy

ACROSTUDY | Pfizer for Professionals Open-label, global, non-interventional, postmarketing surveillance study open to acromegaly patients treated with SOMAVERT (pegvisomant)*; Primary purpose ...