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

Alnylam Pharmaceuticals62 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Interventions

ALN-CC5DRUG

Single or multiple doses of ALN-CC5 by subcutaneous (sc) injection

Sterile Normal Saline (0.9% NaCl)DRUG

calculated volume to match active comparator

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (4)

Clinical Trial Site

Barcelona, Spain

Clinical Trial Site

Leeds, United Kingdom

Covance Clinical Research Unit

Leeds, United Kingdom

Richmond Pharmacology

London, United Kingdom

Outcomes

Primary Outcomes

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)

Time frame: Part A: through day 658; Part B: through day 532; Part C: through day 280

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Part A: through day 70; Part B: through day 140; Part C: through day 140

Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (25-mer)

Data from ClinicalTrials.gov

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