Adalimumab for Mucopolysaccharidosis

Recruiting at 1 trial location

Overseen By Eva Villa-Lopez

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

14 Participants Needed

Trial Summary

What is the purpose of this trial?

Randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of adalimumab compared to placebo on the change from baseline in joint and skeletal disease in children and adults with mucopolysaccharidosis (MPS) I, II or VI.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immune suppression therapy, you must have stopped it at least 1 year before joining the trial.

What data supports the effectiveness of the drug Adalimumab for Mucopolysaccharidosis?

Adalimumab has been shown to be effective in treating conditions like ankylosing spondylitis and juvenile idiopathic arthritis, where it helps reduce symptoms and improve quality of life. This suggests it might also be beneficial for other inflammatory conditions, although specific data for Mucopolysaccharidosis is not available. ^{1 2 3 4 5}

What is the safety profile of Adalimumab (Humira) in humans?

Adalimumab (Humira) is generally safe for humans, but it can cause mild side effects like injection site reactions and upper respiratory infections. Serious side effects are rare but include increased risk of infections like tuberculosis, autoimmune diseases, and certain cancers. Patients should be screened and monitored closely during treatment. ^{6 7 8 9 10}

How does the drug adalimumab differ from other treatments for mucopolysaccharidosis?

Adalimumab is unique because it is a fully human monoclonal antibody that targets and neutralizes tumor necrosis factor (TNF)-alpha, a protein involved in inflammation. While it is commonly used for conditions like rheumatoid arthritis and Crohn's disease, its use for mucopolysaccharidosis is novel, as there are no standard treatments specifically targeting this condition. ^{1 11 12 13 14}

Research Team

Lynda Polgreen, MD, MS

Principal Investigator

The Lundquist Institute at Harbor-UCLA Medical Center

Eligibility Criteria

This trial is for children and adults over 5 years old with Hurler Syndrome, Hunter Syndrome, or Maroteaux-Lamy Syndrome who have either been treated with ERT for at least a year or not treated at all. Participants must have joint motion limitations in at least 3 joints, weigh more than 15 kg, and experience significant pain.

Inclusion Criteria

Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided

I weigh at least 15 kilograms.

I experience more pain than most people do.

Exclusion Criteria

I had a stem cell transplant less than 2 years ago.

I have an active or chronic Hepatitis B infection.

I will not be exposed to live vaccines during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive adalimumab or placebo for 16 weeks to evaluate effects on joint and skeletal disease

16 weeks

Open-label

Participants receive open-label adalimumab treatment for 32 weeks

32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adalimumab

Trial Overview The study tests the safety and effectiveness of Adalimumab injections compared to saline solution (placebo) on joint and skeletal disease in patients with MPS I, II or VI. It's randomized and double-blind: participants don't know if they're getting the real drug or placebo.

Participant Groups

Group I: Open-label adalimumab Experimental Treatment 1 Intervention

Open-label extension of adalimumab dose

Group II: Adalimumab Experimental Treatment 1 Intervention

20 mg subQ every other week (weight 15to \<30 kg) 40 mg subQ every other week (weight ≥30 kg). Non-responders will be escalated to weekly dosing.

Group III: Placebo Placebo Group 1 Intervention

Saline placebo comparator

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?

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Lead Sponsor

Trials

105

Recruited

46,600+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Findings from Research

In a post hoc analysis of the GO-ALIVE study involving 112 ankylosing spondylitis patients, those with early disease showed significantly better responses to IV golimumab compared to those with late disease, indicating that earlier treatment may lead to more effective outcomes.

Patients with early disease experienced higher rates of improvement in disease activity measures at week 16, and while adverse events were reported, they were less frequent in early disease patients (46% vs. 61% in late disease), suggesting a favorable safety profile for early treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Intravenous Golimumab in Ankylosing Spondylitis Patients With Early and Late Disease Through One Year of the GO-ALIVE Study. Deodhar, AA., Shiff, NJ., Gong, C., et al.[2023]

In a study involving 838 patients with polyarticular-course juvenile idiopathic arthritis, adalimumab (ADA) was found to be well tolerated, with no deaths or malignancies reported over a 7-year period.

Patients starting treatment with ADA ± methotrexate showed a trend towards lower disease activity compared to those on methotrexate alone, suggesting ADA may be more effective in managing symptoms in the first year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Adalimumab in Patients With Polyarticular Course of Juvenile Idiopathic Arthritis: STRIVE Registry Seven-Year Interim Results. Brunner, HI., Nanda, K., Toth, M., et al.[2020]

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 involving 15,132 patients with rheumatoid arthritis, adalimumab was found to have a well-established safety profile, with serious infections occurring at a low rate of 4.7 events per 100 patient-years and no significant laboratory abnormalities compared to placebo.

The analysis also indicated that pregnancy outcomes for women exposed to adalimumab were similar to those of unexposed women with rheumatoid arthritis and healthy women, with no increased risk of major birth defects or spontaneous abortions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Burmester, GR., Landewé, R., Genovese, MC., et al.[2022]

In a study of 403 ankylosing spondylitis patients treated with adalimumab over 24 weeks, there was a significant reduction in disease activity, with a mean decrease of 2.0 in BASDAI scores, indicating effective treatment.

The safety profile was acceptable, with serious adverse drug reactions occurring in 3.79% of patients, which aligns with findings from previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of adalimumab for treatment of ankylosing spondylitis in Japan. Kobayashi, S., Kashiwagi, T., Kimura, J.[2020]

Adalimumab has been shown to be generally safe and well tolerated in patients with rheumatoid arthritis, based on safety data from over 10,000 patients and 12,506 patient-years of exposure in clinical trials.

The rate of serious infections was consistent with previous reports, and after implementing tuberculosis screening, the incidence of TB cases decreased significantly, indicating effective monitoring and management of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Schiff, MH., Burmester, GR., Kent, JD., et al.[2022]

Adalimumab, a monoclonal antibody that targets TNF-alpha, has been shown to significantly improve symptoms of rheumatoid arthritis in patients who did not respond adequately to other treatments, with higher response rates (ACR20, ACR50, ACR70) compared to placebo over 24-52 weeks.

The treatment not only provides rapid and sustained efficacy but also slows down joint damage and enhances quality of life, making it a valuable option for adults with active rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of its use in rheumatoid arthritis. Bang, LM., Keating, GM.[2018]

Adalimumab (ADA) is an effective treatment for rheumatoid arthritis (RA) and other inflammatory conditions, and can be used alone or with other medications like methotrexate.

This study compares the safety and effectiveness of ADA with other TNF-α inhibitors, etanercept and infliximab, highlighting the need for more direct comparisons in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab in the treatment of rheumatoid arthritis. Voulgari, PV., Kaltsonoudis, E., Papagoras, C., et al.[2022]

References

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

Adalimumab is effective and well tolerated in treating patients with ankylosing spondylitis who have advanced spinal fusion. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement. [2021]

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

Efficacy and Safety of Intravenous Golimumab in Ankylosing Spondylitis Patients With Early and Late Disease Through One Year of the GO-ALIVE Study. [2023]

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

Safety and Effectiveness of Adalimumab in Patients With Polyarticular Course of Juvenile Idiopathic Arthritis: STRIVE Registry Seven-Year Interim Results. [2020]

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

Randomized, placebo controlled and double-blind trials of efficacy and safety of adalimumab for treating ankylosing spondylitis: a meta-analysis. [2018]

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

Adalimumab: a review of side effects. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

[Safety of adalimumab]. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of adalimumab for treatment of ankylosing spondylitis in Japan. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of its use in rheumatoid arthritis. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Guidance on the use of adalimumab for juvenile idiopathic arthritis in Japan. [2016]

13. England pubmed.ncbi.nlm.nih.gov

Adalimumab in the treatment of rheumatoid arthritis. [2022]

14. England pubmed.ncbi.nlm.nih.gov

VITALITY: impact of adalimumab on health and disability outcomes in patients with Crohn's disease, rheumatoid arthritis, or psoriasis treated in clinical practice in New Zealand. [2020]