A Phase 1/2 Study of an Investigational Drug, ALN-CC5, in Healthy Adult Volunteers and Patients With PNH

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-CC5 in healthy adult volunteers and subjects with PNH

Official Title
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A Phase 1/2 Single-ascending and Multiple-ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-CC5 in Healthy Adult Volunteers and Patients With Paroxysmal Nocturnal Hemoglobinuria

Conditions
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Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention / Treatment
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* Drug: ALN-CC5
* Drug: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adequate complete blood counts, liver and renal function 12-lead electrocardiogram (ECG) within normal limits Female subjects of child bearing potential agreeing to use a protocol specified method of contraception Male subjects agreeing to use protocol specified methods of contraception Willing to provide written informed consent and willing to comply with study requirements Exclusion Criteria: Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study History of multiple drug allergies or intolerance to subcutaneous injection Parts A and B of the study: Used prescription medications within 14 days or 7 half-lives of administration of the first dose of study drug. History of meningococcal infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALN-CC5<br> | Drug: ALN-CC5<br>* Single or multiple doses of ALN-CC5 by subcutaneous (sc) injection<br>|
| Placebo Comparator: Sterile Normal Saline (0.9% NaCl)<br> | Drug: Sterile Normal Saline (0.9% NaCl)<br>* calculated volume to match active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Adverse events were reported for single-ascending doses (SAD) or multiple ascending doses (MAD) of ALN-CC5 when administered to healthy adult subjects and of multiple doses (MD) in patients with paroxysmal nocturnal hemoglobinuria (PNH) | Part A: through day 658; Part B: through day 532; Part C: through day 280 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Alternative Pathway (CAP) | Complement activity was measured in serum samples collected at timepoints throughout the study using the CAP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CAP from baseline. | Part A: through day 70; Part B: through day 140; Part C: through day 140 | 
| Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Classical Pathway (CCP) | Complement activity was measured in serum samples collected at time points throughout the study using the CCP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CCP from baseline. | Part A: through day 70; Part B: through day 140; Part C: through day 140 | 
| Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in C5 Protein Levels | Total C5 protein levels were measured in serum samples collected at time points throughout the study using a mass spectrometry-based method. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in C5 protein level from baseline. | Part A: through day 70; Part B: through day 140; Part C: through day 140 | 
| Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (25-mer) | Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 25-mer. | Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84 | 
| Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (23-mer) | Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 23-mer. | Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84 | 
| Pharmacokinetic (PK) Effect of ALN-CC5: T Max (25-mer) | Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 25-mer. | Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84 | 
| Pharmacokinetic (PK) Effect of ALN-CC5: T Max (23-mer) | Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 23-mer. | Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84 | 
| Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (25-mer) | Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 25-mer. | Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84 | 
| Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (23-mer) | Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 23-mer. | Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84 | 

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