LAD603 for Healthy Adults

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Almirall, S.A.

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called LAD603 in healthy adults to see if it is safe and how the body handles it. Researchers will give different doses to check for side effects and how the drug is processed.

Do I have to stop taking my current medications for this trial?

Yes, you must stop taking any medications, including over-the-counter ones, at least 14 days before the trial starts, unless the investigator decides they won't interfere with the study. Hormonal contraceptives and acetaminophen (up to 2 grams per day) are exceptions.

What data supports the idea that LAD603 for Healthy Adults is an effective drug?

The available research does not provide specific data on LAD603 for Healthy Adults. Instead, it focuses on other treatments for rheumatoid arthritis, such as upadacitinib and tofacitinib. Upadacitinib showed improvements in patient-reported outcomes, indicating it might be effective for those who did not respond well to other drugs. However, there is no direct information on LAD603's effectiveness. ^{1 2 3 4 5}

What safety data exists for the treatment LAD603?

The provided research does not contain specific safety data for LAD603. It discusses safety data related to antihypertensive trials, adverse drug reactions in older adults, and safety-related drug label changes for cardiometabolic agents, but none of these directly mention LAD603 or provide safety data for it. ^{6 7 8 9 10}

Is the treatment LAD603 a promising treatment for healthy adults?

The information provided does not directly mention LAD603 or its effects. However, it discusses the benefits of omega-3 fatty acids, which are known to improve muscle strength and reduce inflammation in older adults. If LAD603 is related to omega-3 fatty acids, it might be promising for improving muscle function and reducing inflammation. ^{11 12 13 14 15}

Research Team

Eligibility Criteria

This trial is for healthy adults who can participate in a study to assess the safety and effects of a new medication, LAD603. Specific eligibility details are not provided, but typically participants must meet certain health standards and have no conflicting medical conditions.

Inclusion Criteria

I am willing to join the study and have signed all necessary consent forms.

My BMI is between 18.5 and 29.9, and I weigh at least 60 kg.

I am a male who has had a vasectomy or will use contraception and avoid sperm donation during the study.

Exclusion Criteria

I have had cancer or a related disease in the last 5 years, except for certain skin cancers or cervical cancer in situ that were successfully treated.

I have a history of tuberculosis or have been in close contact with someone who has active tuberculosis.

My heart rate or blood pressure readings were abnormal during my initial check-up.

Treatment Details

Interventions

• LAD603 (Monoclonal Antibodies)

Trial Overview The study is testing LAD603 against a placebo to see how safe it is and how the body responds to different doses. It's divided into two parts: one where subjects receive a single dose, and another with multiple doses over time.

Participant Groups

Group I: Part 2: (LAD603) Cohort D Experimental Treatment 1 Intervention

Participants will receive multiple ascending dose of LAD603 SC injection on Days 1, 15, 18 and 22.

Group II: Part 2: (LAD603) Cohort C Experimental Treatment 1 Intervention

Participants will receive multiple ascending dose of LAD603 SC injection on Days 1, 15, 18 and 22.

Group III: Part 2: (LAD603) Cohort B Experimental Treatment 1 Intervention

Participants will receive multiple ascending dose of LAD603 SC injection on Days 1, 15, 18 and 22.

Group IV: Part 2: (LAD603) Cohort A Experimental Treatment 1 Intervention

Participants will receive multiple ascending dose of LAD603 SC injection on Days 1, 15, 18 and 22.

Group V: Part 1: (LAD603) Cohort 8 Experimental Treatment 1 Intervention

Participants will receive single ascending dose of LAD603 SC injection on Day 1.

Group VI: Part 1: (LAD603) Cohort 7 Experimental Treatment 1 Intervention

Participants will receive single ascending dose of LAD603 SC injection on Day 1.

Group VII: Part 1: (LAD603) Cohort 6 Experimental Treatment 1 Intervention

Participants will receive single ascending dose of LAD603 SC injection on Day 1.

Group VIII: Part 1: (LAD603) Cohort 5 Experimental Treatment 1 Intervention

Participants will receive single ascending dose of LAD603 SC injection on Day 1.

Group IX: Part 1: (LAD603) Cohort 4 Experimental Treatment 1 Intervention

Participants will receive single ascending dose of LAD603 SC injection on Day 1.

Group X: Part 1: (LAD603) Cohort 3 Experimental Treatment 1 Intervention

Participants will receive single ascending dose of LAD603 SC injection on Day 1.

Group XI: Part 1: (LAD603) Cohort 2 Experimental Treatment 1 Intervention

Participants will receive single ascending dose of LAD603 SC injection on Day 1.

Group XII: Part 1: (LAD603) Cohort 1 Experimental Treatment 1 Intervention

Participants will receive single ascending dose of LAD603 SC injection on Day 1.

Group XIII: Part 2: Placebo Placebo Group 1 Intervention

Participants will receive multiple ascending dose of matching placebo SC injection on Days 1, 8 15, and 22.

Group XIV: Part 1: Placebo Placebo Group 1 Intervention

Participants will receive single ascending dose of matching placebo SC injection on Day 1.

Who Is Running the Clinical Trial?

Almirall, S.A.

Lead Sponsor

Trials

63

Recruited

19,200+

Carlos Gallardo Piqué

Almirall, S.A.

Chief Executive Officer since 2023

MS in Industrial Engineering from Universitat Politècnica de Catalunya, MBA from Stanford Graduate School of Business

Mercedes Diz

Almirall, S.A.

Chief Medical Officer since 2023

PhD in Biochemistry

Findings from Research

In a study of 498 patients with rheumatoid arthritis who did not respond adequately to biologic treatments, both doses of upadacitinib (15 mg and 30 mg) significantly improved patient-reported outcomes (PROs) such as pain, disability, and overall disease activity compared to placebo.

More patients taking upadacitinib reported clinically meaningful improvements in quality of life measures, with the number needed to treat (NNT) to achieve these improvements ranging from 4 to 7, indicating that upadacitinib is effective in enhancing the well-being of patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs. Strand, V., Schiff, M., Tundia, N., et al.[2023]

In a post hoc analysis of two phase III studies involving rheumatoid arthritis patients, early lack of improvement in disease activity after 1 or 3 months of tofacitinib treatment was linked to a low likelihood of achieving low disease activity (LDA) by month 6.

Specifically, patients who did not show significant improvement (CDAI ≥6) at month 3 had very low chances of reaching LDA at month 6, suggesting that early response to tofacitinib is crucial for determining the continuation of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Probability of Achieving Low Disease Activity at Month 6. van Vollenhoven, RF., Lee, EB., Fallon, L., et al.[2020]

In a study of 250 patients with active rheumatoid arthritis, the minimal clinically important improvements (MCIIs) in pain and physical functioning were found to be larger in groups receiving more effective treatments, such as prednisone, compared to those receiving less impactful interventions.

The study demonstrated that MCIIs are not fixed values but vary based on the responsiveness of the sample, indicating that higher treatment effectiveness leads to greater perceived improvements in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimates of minimal clinically important improvments vary with the responsiveness of the sample. Ward, MM., Alba, MI.[2023]

In a post hoc analysis of five phase 3 clinical trials involving 3117 patients with rheumatoid arthritis, upadacitinib treatment led to 32-52% of patients achieving remission as measured by the RAPID3 score after 60 weeks.

RAPID3 scores showed a strong correlation with other established disease activity measures (CDAI, SDAI, DAS28[CRP]), indicating that upadacitinib effectively reduces disease activity in rheumatoid arthritis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials. Bergman, M., Buch, MH., Tanaka, Y., et al.[2022]

The study determined the minimal clinically important difference (MCID) for the Aberrant Behaviour Checklist-Irritability (ABC-I), which is crucial for assessing improvements in aggressive behavior among individuals with intellectual disabilities, based on data from 15 randomized controlled trials.

The estimated MCID values varied significantly between methods, with a meta-analysis suggesting a range of 0.05 to 4.94, while anchor-based methods indicated a larger change of 6.6 to 16.6, highlighting the importance of method selection in interpreting intervention outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimation of the minimal clinically important difference on the Aberrant Behaviour Checklist-Irritability (ABC-I) for people with intellectual disabilities who display aggressive challenging behaviour: A triangulated approach. Hassiotis, A., Melville, C., Jahoda, A., et al.[2022]

Older-people's trials of antihypertensive drugs showed a higher rate of Serious Adverse Events (SAEs) compared to standard trials, with 0.18 versus 0.11 events per person per year, indicating that older participants may experience more complications during treatment.

The rate of hospitalizations and deaths in the community for those taking RAAS antihypertensives was significantly higher than the SAEs reported in both standard and older-people's trials, suggesting that trial results may not fully represent the risks faced by older patients in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Representativeness of antihypertensive trials: analysis of serious adverse events. Hanlon, P., Shah, A., Mair, F., et al.[2023]

From 2000 to 2016, the number of adverse drug reaction (ADR) reports for older adults increased significantly, with the highest rates observed in those aged 70-84, indicating a growing concern for drug safety in this age group.

Older adults experienced fatal outcomes from ADRs almost three times more often than younger adults, highlighting the need for careful monitoring, especially for commonly used medications like antithrombotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in older adults: a retrospective comparative analysis of spontaneous reports to the German Federal Institute for Drugs and Medical Devices. Dubrall, D., Just, KS., Schmid, M., et al.[2023]

A study of 55 large clinical trials involving over 402,000 patients found that 69% resulted in updates to the safety information on drug labels for cardiometabolic agents, indicating that these trials can provide valuable safety data post-approval.

However, the overall contribution of these trials to new safety information was limited, with only 35% leading to changes in adverse drug reactions, suggesting that selective safety data collection may not significantly enhance safety knowledge for drugs already studied extensively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety-Related Drug Label Changes Following Large Post-Marketing Cardiometabolic Trials: A Review of European Public Assessment Reports. Starokozhko, V., Tarrahi, F., Vrijlandt, PJWS., et al.[2023]

In a systematic review of 38 studies involving 2857 older adults, colistin-based therapy did not show a significant difference in 1-month mortality compared to other treatment regimens for infections.

However, colistin was associated with a higher likelihood of clinical failure and a significantly increased risk of acute kidney injury, indicating the need for careful monitoring of kidney function in elderly patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of colistin among older adults: a systematic review and meta-analysis. Margalit, I., Prendki, V., Tishler, O., et al.[2022]

From 1981 to 2002, the rate of hospital admissions due to adverse drug reactions (ADRs) in people aged 60 and over in Western Australia increased significantly, from 2.5 to 12.9 per 1000 person-years, with the most dramatic rise seen in patients aged 80 and older.

Cardiovascular agents were the most commonly implicated drugs in ADRs, with anticoagulants, cytotoxics, and antirheumatics also frequently causing issues, highlighting the need for updated clinical guidelines to address the rising trend in ADRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in older Australians, 1981-2002. Burgess, CL., Holman, CD., Satti, AG.[2020]

This systematic review aims to evaluate the effects of omega-3 polyunsaturated fatty acid supplementation on muscle mass, strength, inflammatory biomarkers, and physical activity in medically stable older adults, using data from randomized controlled trials.

The review will synthesize findings from various studies to determine the efficacy of omega-3 supplementation, with outcomes including muscle strength and inflammatory markers, providing valuable insights into its potential benefits for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dietary omega-3 fatty acid supplementation on frailty-related phenotypes in older adults: a systematic review and meta-analysis protocol. Stocks, J., Valdes, AM.[2021]

In a 6-month randomized controlled trial involving 63 healthy older adults, supplementation with 4 g/day of omega-3 polyunsaturated fatty acids (n3-PUFA) led to a significant increase in muscle strength compared to a corn oil placebo, with a 7.5% increase in strength for the n3-PUFA group versus 3.1% for the placebo group.

Despite the improvements in muscle strength, n3-PUFA supplementation did not significantly affect mitochondrial function or the acute exercise response, indicating that while it may help with muscle function, its effects on overall muscle metabolism and exercise responsiveness may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Trial of the Effects of Dietary n3-PUFAs on Skeletal Muscle Function and Acute Exercise Response in Healthy Older Adults. Kunz, HE., Michie, KL., Gries, KJ., et al.[2023]

In a study of 130 postmenopausal women, those with sarcopenic obesity (SO) had significantly higher levels of the inflammatory marker IL-6 compared to those without SO, indicating a link between SO and inflammation.

Both IL-6 and CRP levels were correlated with body composition metrics such as fat mass and waist circumference, suggesting that higher inflammation may contribute to the health risks associated with SO in older women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between sarcopenic obesity-related phenotypes and inflammatory markers in postmenopausal women. Dutra, MT., Avelar, BP., Souza, VC., et al.[2022]

In a study of 463 older adults aged 70-79, no significant relationship was found between IL-6 gene variations and levels of the inflammatory cytokine IL-6, muscle strength, or frailty, suggesting that these genetic factors may not influence these health outcomes.

Further analysis in a separate cohort of 266 individuals confirmed the lack of association, indicating that elevated IL-6 levels and related health issues in older women may not be linked to genetic variations in the IL-6 gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women. Walston, J., Arking, DE., Fallin, D., et al.[2022]

In a study comparing 6-month-old and 24-month-old male mice, researchers found that certain metabolites derived from polyunsaturated fatty acids, particularly arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, were significantly higher in the skeletal muscle of older, sarcopenic mice.

The identification of nine specific metabolites that accumulate in aged muscle may help to better understand the mechanisms behind sarcopenia, potentially leading to new strategies for addressing age-related muscle loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accumulation of polyunsaturated fatty acid-derived metabolites in the sarcopenic muscle of aging mice. Kadoguchi, T., Shimada, K., Fukui, N., et al.[2023]

References

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

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs. [2023]

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

Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Probability of Achieving Low Disease Activity at Month 6. [2020]

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

Estimates of minimal clinically important improvments vary with the responsiveness of the sample. [2023]

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

Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials. [2022]

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

Estimation of the minimal clinically important difference on the Aberrant Behaviour Checklist-Irritability (ABC-I) for people with intellectual disabilities who display aggressive challenging behaviour: A triangulated approach. [2022]

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

Representativeness of antihypertensive trials: analysis of serious adverse events. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in older adults: a retrospective comparative analysis of spontaneous reports to the German Federal Institute for Drugs and Medical Devices. [2023]

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

Safety-Related Drug Label Changes Following Large Post-Marketing Cardiometabolic Trials: A Review of European Public Assessment Reports. [2023]

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

Effectiveness and safety of colistin among older adults: a systematic review and meta-analysis. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in older Australians, 1981-2002. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Effect of dietary omega-3 fatty acid supplementation on frailty-related phenotypes in older adults: a systematic review and meta-analysis protocol. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

A Randomized Trial of the Effects of Dietary n3-PUFAs on Skeletal Muscle Function and Acute Exercise Response in Healthy Older Adults. [2023]

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

Relationship between sarcopenic obesity-related phenotypes and inflammatory markers in postmenopausal women. [2022]

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

IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women. [2022]

15. Japan pubmed.ncbi.nlm.nih.gov

Accumulation of polyunsaturated fatty acid-derived metabolites in the sarcopenic muscle of aging mice. [2023]