Adalimumab for Enlarged Prostate

Overseen By Malgorzata Antoniak, Ph.D.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: NorthShore University HealthSystem

Must not be taking: TNF inhibitors, Chemotherapy

Disqualifiers: Autoimmune diseases, Cancer, Infections, others

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

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: 12

Duration: 24 weeks

70 Participants Needed

Trial Summary

What is the purpose of this trial?

Specific Aim 1. To evaluate the efficacy of TNF antagonist action in BPH/LUTS Specific Aim 2. Define the consequences of TNF antagonist therapy on prostate tissue Specific Aim 3. Identify genetic predictors to stratify patients with differential response to TNF-antagonist therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently on a TNF inhibitor or undergoing cancer therapy, you would not be eligible to participate.

Is adalimumab generally safe for humans?

Adalimumab (Humira) is generally considered safe for humans, but it can cause some side effects. Common side effects include reactions at the injection site and mild infections, while serious side effects, though rare, can include serious infections like tuberculosis, autoimmune diseases, and certain types of cancer. Patients should be screened and monitored closely during treatment. ^{1 2 3 4 5}

How does the drug Adalimumab differ from other treatments for enlarged prostate?

Adalimumab (Humira) is unique for treating an enlarged prostate because it is primarily an anti-inflammatory drug used for autoimmune conditions, unlike traditional treatments that focus on hormone manipulation or surgery. This novel approach may offer a different mechanism of action by targeting inflammation, which is not typically addressed by standard prostate treatments. ^{6 7 8 9 10}

Research Team

Alexander Glaser, MD

Principal Investigator

Endeavor Health

Simon W Hayward, Ph.D

Principal Investigator

Endeavor Health

Eligibility Criteria

Men aged 50-75 with a prostate volume ≥ 80mL and moderate to severe urinary symptoms (IPSS ≥ 8), diagnosed with BPH, scheduled for surgery, who haven't used TNF inhibitors like adalimumab before. Excludes those with catheter-dependent urinary retention, active infections or cancer, recent pelvic surgeries, autoimmune diseases, certain neurological/psychiatric disorders or substance abuse.

Inclusion Criteria

I have been diagnosed with an enlarged prostate.

I have never been treated with TNF inhibitors.

You are committed to residing in the study area for the next half-year.

Exclusion Criteria

I have visible blood in my urine.

I am currently undergoing chemotherapy or other cancer treatments.

I have been diagnosed with interstitial cystitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adalimumab 40 mg or placebo injection every 2 weeks

24 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adalimumab

Trial Overview The trial is testing the effectiveness of Adalimumab, a TNF blocker medication on men with enlarged prostates causing urinary issues. It aims to assess symptom relief post-treatment and identify genetic markers predicting patient response.

Participant Groups

Group I: Placebo Active Control 1 Intervention

placebo injection (saline) every 2 weeks.

Group II: adalimumab Active Control 1 Intervention

adalimumab 40 mg every 2 weeks

Adalimumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in United States as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis
• Hidradenitis suppurativa

Approved in Canada as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in Japan as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

NorthShore University HealthSystem

Lead Sponsor

Trials

134

Recruited

740,000+

Endeavor Health

Lead Sponsor

Trials

135

Recruited

742,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Adalimumab is an effective treatment for rheumatoid arthritis and is expected to be approved for other conditions like psoriasis and ankylosing spondylitis, with a favorable side effect profile compared to traditional treatments, as it does not require regular lab monitoring.

However, it carries a two-fold increased risk of serious infections, particularly tuberculosis, and should not be used during active infections; careful screening and monitoring for side effects are essential for safe use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of side effects. Scheinfeld, N.[2022]

Adalimumab is generally safe for treating psoriasis, with most side effects being mild, such as injection site reactions and upper respiratory infections, which typically do not require stopping the medication.

Serious adverse effects, although rare, can include severe infections and autoimmune conditions, highlighting the need for careful patient screening and monitoring during treatment and for five months afterward.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of adalimumab]. Ferran, M., Pujol, RM.[2015]

In a study of 100 patients with active psoriatic arthritis who did not respond adequately to DMARDs, adalimumab significantly improved symptoms, with 39% of patients achieving an ACR20 response compared to 16% in the placebo group after 12 weeks.

Adalimumab was well tolerated, with similar rates of serious adverse events between the treatment and placebo groups, and no serious infections reported during therapy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. Genovese, MC., Mease, PJ., Thomson, GT., et al.[2022]

Adalimumab effectively targets and neutralizes tumor necrosis factor (TNF), a key player in psoriatic arthritis (PsA), leading to significant reductions in both joint and skin symptoms in clinical trials.

The treatment not only improved symptoms but also inhibited structural damage and enhanced patients' quality of life and disability measures, with a good safety profile reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab: an anti-TNF agent for the treatment of psoriatic arthritis. Mease, PJ.[2019]

In a study of 2057 patients with moderately to severely active Crohn's disease, adalimumab (Humira) significantly improved disease outcomes over 6 years, with remission rates increasing from 29% at baseline to 75% by year 6.

The treatment was associated with low rates of serious infections and no new safety concerns, indicating that adalimumab is both effective and safe for long-term use in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab Effectiveness Up to Six Years in Adalimumab-naïve Patients with Crohn's Disease: Results of the PYRAMID Registry. Loftus, EV., Reinisch, W., Panaccione, R., et al.[2020]

In a pilot phase II study involving eight Black men with metastatic castrate-resistant prostate cancer (mCRPC), the PD-L1 inhibitor avelumab did not achieve the primary endpoint of a 50% reduction in prostate-specific antigen (PSA) levels after 8 weeks, indicating a lack of clinical efficacy.

The study was halted early due to safety concerns, as patients experienced rapid clinical progression, with a median time to PSA progression of only 35 days, suggesting that avelumab may not be a suitable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Black Patients with Metastatic Castrate-Resistant Prostate Cancer Have a Shorter Time Interval Between PSA and Clinical Progression on Novel Hormonal Therapies plus Avelumab. Hawkins, CM., Barata, PC., Cotogno, P., et al.[2023]

Combining atezolizumab, an anti-PD-L1 immunotherapy, with enzalutamide, an androgen receptor antagonist, did not improve survival rates in patients with metastatic prostate cancer.

Further research is needed to understand the mechanisms of resistance to immunotherapy in the prostate tumor microenvironment, which may help improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer. Siddiqui, BA., Subudhi, SK., Sharma, P.[2023]

Immunotherapy shows promise as a new treatment option for metastatic prostate cancer, potentially delaying disease progression with minimal toxicity compared to traditional therapies like chemotherapy and androgen-deprivation therapy.

Current phase III clinical trials are exploring various immunotherapy strategies, including immune-modulating agents and combination therapies, indicating a growing interest in developing safer and more effective treatments for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for prostate cancer - recent progress in clinical trials. Kipp, RT., McNeel, DG.[2007]

The IMbassador250 trial involving 759 men with metastatic castration-resistant prostate cancer found that adding atezolizumab to enzalutamide did not improve overall survival, although it had an acceptable safety profile.

However, patients with high levels of PD-L1 expression and certain immune gene signatures showed longer progression-free survival, suggesting that careful patient selection could enhance the effectiveness of immune checkpoint inhibitors in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Powles, T., Yuen, KC., Gillessen, S., et al.[2023]

This systematic review analyzed 24 prostate cancer patients and found that immunotherapies, particularly IMM-101, showed promising results with a mean overall survival (OS) of 56 months, indicating potential benefits for patients.

Among the immunotherapies studied, Pembrolizumab and IMM-101 were the most commonly used, highlighting their relevance in the treatment landscape for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. Ashraf, MU., Farwa, U., Siddiqa, M., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of side effects. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

[Safety of adalimumab]. [2015]

3. Canada pubmed.ncbi.nlm.nih.gov

Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Adalimumab: an anti-TNF agent for the treatment of psoriatic arthritis. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Adalimumab Effectiveness Up to Six Years in Adalimumab-naïve Patients with Crohn's Disease: Results of the PYRAMID Registry. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Black Patients with Metastatic Castrate-Resistant Prostate Cancer Have a Shorter Time Interval Between PSA and Clinical Progression on Novel Hormonal Therapies plus Avelumab. [2023]

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

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer. [2023]

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

Immunotherapy for prostate cancer - recent progress in clinical trials. [2007]

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

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. [2023]

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

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. [2023]