Study of ALXN1820 in Healthy Adult Participants
Study Details
Study Description
Brief Summary
This is a Phase 1, randomized, double-blind, placebo-controlled single and multiple ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of ALXN1820 administered subcutaneously (SC) (ALXN1820 SC) and intravenously (IV) (ALXN1820 IV).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This study will include up to 10 different dosing cohorts, with each cohort consisting of 2 groups (ALXN1820 group, placebo group). Participants will be randomly assigned in a 3:1 ratio to each of these 2 groups, respectively, within all 10 cohorts, to receive either a single or multiple doses of ALXN1820 SC, a single dose of ALXN1820 IV, or a single or multiple doses of placebo.
The study will be conducted in healthy adult participants and will also include a multiple SC dose cohort in healthy participants of Japanese descent.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ALXN1820 Participants will receive ALXN1820 SC or ALXN1820 IV according to their assigned cohort. ALXN1820 SC will be evaluated in single and multiple ascending doses while ALXN1820 IV will be evaluated in a single dose cohort only. |
Drug: ALXN1820 SC
ALXN1820 SC will be administered as a manual SC push or SC infusion via a syringe pump. Doses will range from 12.5 milligrams (mg) to a maximum of 2250 mg. Multiple dosing duration will range from 3 to 5 weeks.
Drug: ALXN1820 IV
ALXN1820 IV (450 mg) will be administered as an IV infusion.
|
| Placebo Comparator: Placebo Participants will receive Placebo SC or Placebo IV according to their assigned cohort. |
Drug: Placebo SC
Placebo SC will be administered as a manual SC push or SC infusion via a syringe pump.
Drug: Placebo IV
Placebo IV will be administered as an IV infusion.
|
Outcome Measures
Primary Outcome Measures
- Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV [Up to 154 days postdose]
Adverse events will be assessed using the Common Terminology Criteria for Adverse Events, version 4.0.
Secondary Outcome Measures
- Area Under The Concentration-time Curve From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) Of Serum ALXN1820 For Single And Multiple Ascending Doses [Up to 154 days postdose]
- Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single And Multiple Ascending Doses [Up to 154 days postdose]
- Change From Baseline In Serum Concentrations Of Total And Free Properdin For ALXN1820 SC And ALXN1820 IV [Up to 154 days postdose]
- Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV [Up to 154 days postdose]
- Incidence Of Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV [Up to 154 days postdose]
- Absolute Bioavailability Of ALXN1820 SC [Up to 126 days postdose]
The absolute bioavailability for the ALXN1820 SC cohorts will be defined by the ratio of the geometric means for the AUC0-inf parameter for the ALXN1820 SC cohort over the ALXN1820 IV cohort after a single dose.
- Comparison Of Incidence Of TEAEs For ALXN1820 SC For Multiple Ascending Doses Between Healthy Non-Japanese Participants And Participants Of Japanese Descent [Up to 154 days postdose]
- Comparison Of AUCtau Of Serum ALXN1820 SC For Multiple Ascending Doses Between Healthy Non-Japanese Participants And Participants Of Japanese Descent [Up to 154 days postdose]
- Comparison Of Cmax Of Serum ALXN1820 SC For Multiple Ascending Doses Between Healthy Non-Japanese Participants And Participants Of Japanese Descent [Up to 154 days postdose]
- Comparison Of Incidence of ADAs To ALXN1820 SC Between Healthy Non-Japanese Participants And Participants Of Japanese Descent [Up to 154 days postdose]
- Comparison Of The Change From Baseline In CAP Activity Using The Wieslab AP Assay Between Healthy Non-Japanese Participants And Participants Of Japanese Descent For Multiple Ascending Doses Of ALXN1820 SC [Up to 154 days postdose]
- Comparison In The Change From Baseline In Serum Concentrations Of Total And Free Properdin Between Healthy Non-Japanese Participants And Participants Of Japanese Descent For Multiple Ascending Doses Of ALXN1820 SC [Up to 154 days postdose]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Body weight 50 to 100 kilograms (kg); body mass index 17 to 30 kg/meter squared.
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Cohort 9 only: Japanese participants (defined as those participants whose parents and grandparents are both Japanese and who have spent less than 5 years outside of Japan).
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Satisfactory medical assessment.
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Must follow protocol-specified contraception guidance while on treatment and for up to 6 months after last dose.
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Vaccination requirement:
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Vaccination with tetravalent meningococcal conjugate vaccine at least 56 days and not more than 2 years, 6 months prior to dosing;
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Vaccination with serogroup B meningococcal vaccine at least 56 days prior to dosing, with a booster at least 28 days prior to dosing, with at least 28 days between the first and second injections.
Exclusion Criteria:
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Current/recurrent diseases or relevant medical history.
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History of any Neisseria infection.
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Hepatitis B/C, human immunodeficiency virus.
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History of latent or active tuberculosis (TB), or positive TB test.
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Active systemic infection within 14 days of dosing.
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Risk of meningococcal infections due to living/working conditions.
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History of complement deficiency or complement activity below the reference range.
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Participation in a clinical study within 90 days or 5 half lives of the investigational agent (whichever is longer) before initiation of dosing on Day 1.
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Participation in more than 1 clinical study of a monoclonal antibody (mAb), or participation in a clinical study of a mAb within the 6 months or 5 half lives of the mAb (whichever is longer) prior to screening.
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Acquired complement deficiencies (for example, those receiving eculizumab).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Study Site | Herston | Australia | 4006 | |
| 2 | Clinical Study Site | London | United Kingdom | SE1 1YR |
Sponsors and Collaborators
- Alexion Pharmaceuticals
- Syneos Health
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALXN1820-HV-101