LAD603 for Healthy Adults

Overseen By Laura Vidal Gispert

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Almirall, S.A.

Must not be taking: Antimicrobials, Antivirals, Antiparasitics, Antiprotozoals

Disqualifiers: Cancer, Cardiovascular, Hepatitis, others

Compensation: Varies

Number of Visits: 5

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LAD603 to determine its safety and tolerance in the body. Researchers will examine how the treatment behaves and whether it triggers any unwanted immune reactions. The trial includes different groups, with some receiving various doses of LAD603 and others receiving a placebo (a substance with no active drug). It targets healthy adults who are comfortable with study requirements and have no significant health issues. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Will I have to stop taking my current medications?

Yes, participants must stop taking any medications, including over-the-counter ones, at least 14 days before the study starts, unless the study doctor decides it won't interfere with the study or affect safety. Hormonal contraceptives and acetaminophen (up to 2 grams per day) are allowed.

Is there any evidence suggesting that LAD603 is likely to be safe for humans?

Research shows that earlier studies on LAD603 found it safe and well-tolerated in humans when given as a single dose. Participants did not experience serious side effects with a small amount of the treatment. Common side effects of similar treatments include fever, tiredness, diarrhea, and immune-related issues like thyroid problems or lung inflammation. Monitoring these side effects is important, but they are usually manageable.

This trial is in its early phase, focusing on safety. While LAD603 appears promising, researchers are still carefully studying its safety in humans. So far, earlier studies have shown no evidence of severe side effects at the tested doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about LAD603 because it introduces a novel mechanism of action that sets it apart from typical treatments for various conditions, which usually include established drugs or therapies that have been used for years. LAD603 is administered as a subcutaneous injection, potentially offering a more targeted and efficient delivery compared to oral medications or intravenous therapies. This approach could lead to faster onset of effects and improved patient compliance due to the convenience of the injection method. Additionally, the ascending dosage strategy in the trial aims to optimize effectiveness while monitoring safety, which could lead to more personalized treatment regimens in the future.

What evidence suggests that LAD603 could be effective?

Researchers are studying LAD603 to determine its safety and how the body processes it. In this trial, participants will join different treatment arms, receiving either single or multiple ascending doses of LAD603 or a placebo. Researchers are testing this drug in healthy adults at various doses to understand its effects better. Current studies focus on safety and dosage, so there is no specific information yet on its effectiveness for any medical condition. However, researchers are interested in its potential, and these early tests are crucial for future research. Understanding how LAD603 works in healthy individuals is a key step toward exploring its future benefits. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Single Ascending Dose

Participants receive single ascending doses of LAD603 or placebo

8 weeks

1 visit per cohort (in-person)

Part 2: Multiple Ascending Dose

Participants receive multiple ascending doses of LAD603 or placebo

14 weeks

4 visits (in-person) on Days 1, 8, 15, and 22

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LAD603

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

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 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]

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]

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 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]

Citations

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A Single and Multiple Ascending Dose Study of LAD603 in ... This is a 2-part study. Part 1 will comprise up to 8 cohorts of healthy adult participants and investigate single ascending doses of LAD603.

2. withpower.com withpower.com/trial/phase-1-healthy-subjects-hs-11-2023-f465b

LAD603 for Healthy Adults 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 ...

3. go.drugbank.com go.drugbank.com/conditions/DBCOND0114743

Healthy Volunteers (HV) (DBCOND0114743) A Single and Multiple Ascending Dose Study of LAD603 in Healthy Subjects. LAD603. treatment, 1, recruiting. NCT03653897. Performance of the ID-Cap System, an ...

4. linknovate.com linknovate.com/clinical-trial/a-phase-1-randomized-2-part-single-blind-placebo-controlled-single-and-multiple-ascending-dose-study-to-assess-safety-tolerability-pharmacokinetics-immunogenicity-and-pharmacodynamics-of-lad603-in-healthy-adult-subjects-521083/?text=participant

A Phase 1 Randomized, 2-part, Single-blind, Placebo ... This is a 2-part study. Part 1 will comprise up to 8 cohorts of healthy adult participants and investigate single ascending doses of LAD603. Part 2 will ...

5. clinconnect.io clinconnect.io/trials/NCT03237832

A Phase 1 Study of ARN-6039 (NCT03237832 ... - ClinConnect This Phase 1 study intends to determine the safety and tolerability of ARN-6039 in healthy subjects.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11270294/

Adverse Events of PD-1, PD-L1, CTLA-4, and LAG-3 ... Consistently reported AEs included pyrexia, fatigue, diarrhea, and immune-related AEs such as hypothyroidism and pneumonitis and are congruent ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39051335/

Adverse Events of PD-1, PD-L1, CTLA-4, and LAG-3 ... This study aimed to identify the 25 most prevalent adverse events (AEs) associated with FDA-approved immune checkpoint inhibitors ...

8. pharmacy.wsu.edu pharmacy.wsu.edu/documents/2022/04/dic-newsletter-03-2022.pdf/

Drug Information Center Highlights of FDA Activities – 3/1/22 Severe Adverse Effects. Serious adverse reactions occurred in 36% of patients: hemorrhage, musculoskeletal pain, sepsis, anemia, urinary tract infection ...