Safety and Pharmacokinetics of TT30 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study Overview
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Brief Summary
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The purpose of this research study is to understand the safety, pharmacokinetics and pharmacodynamics of a single dose of TT30 (ALXN1102 and ALXN1103 formulations) when given IV (through a vein) or SC (under the skin) to patients with PNH.

Detailed Description
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This is an open-label, single-dose, dose-escalation study to assess the safety, tolerability, PK, PD, and immunogenicity of TT30 given as an IV infusion and as a SC injection in subjects with PNH or evidence of circulating PNH cells. Eligible subjects with PNH will be vaccinated with meningococcal vaccine at least two weeks prior to dosing (if not previously vaccinated or if revaccination is required). On study day 1, the subject will receive the single dose of TT30 as an IV infusion over 60 minutes or as a SC injection, and be followed with additional study evaluations over the next 59 days.

Official Title
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A Phase 1, Single Ascending Dose Study of the Safety and Pharmacokinetics of TT30 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Conditions
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Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention / Treatment
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* Drug: ALXN1102
* Drug: ALXN1103


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals at least 18 years of age with a diagnosis of PNH & vaccination against meningococcus. Exclusion Criteria: Abnormal renal or liver function History of meningococcal disease History of Guillain-Barre syndrome Known infection with HIV or Hepatitis B or C History of thrombotic events

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TT30 (ALXN1102 Formulation)<br>IV: 0.1, 0.3, and 1.0 mg/kg | Drug: ALXN1102<br>* Single Ascending Dose IV<br>|
| Experimental: TT30 (ALXN1103 Formulation)<br>IV: 3.0, 6.0, and 10.0 mg/kg SC: 1.0 and 3.0 mg/kg | Drug: ALXN1103<br>* Single Ascending Dose IV or SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of a single dose of TT30. | Safety and tolerability will be evaluated in all subjects by physical exam, vital signs, ECGs, laboratory changes over time, adverse events, and antibody development. | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize PK, PD and immunogenicity of a single dose of TT30. | Immunogenicity will be will be assessed using standard measures for these parameters. PK and PD will be assessed by using standard measures, including reticulocyte count and lactate dehydrogenase (LDH) levels. | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PNH