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

Phase 1

Completed

Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Interventions: Drug: Sterile Normal Saline (0.9% NaCl)
Drug: ALN-CC5

Registration Number: NCT02352493

Lead Sponsor: Alnylam Pharmaceuticals

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 62

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sterile Normal Saline (0.9% NaCl)	Sterile Normal Saline (0.9% NaCl)	-
ALN-CC5	ALN-CC5	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	Part A: through day 658; Part B: through day 532; Part C: through day 280	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)

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Alternative Pathway (CAP)	Part A: through day 70; Part B: through day 140; Part C: through day 140	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.
Pharmacokinetic (PK) Effect of ALN-CC5: T Max (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	Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 23-mer.
Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (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	Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 23-mer.
Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (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	Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 25-mer.
Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in C5 Protein Levels	Part A: through day 70; Part B: through day 140; Part C: through day 140	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.
Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Classical Pathway (CCP)	Part A: through day 70; Part B: through day 140; Part C: through day 140	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.
Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (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	Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 23-mer.
Pharmacokinetic (PK) Effect of ALN-CC5: T Max (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	Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 25-mer.
Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (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	Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 25-mer.

Trial Locations

Locations (3): Richmond Pharmacology
🇬🇧
London, United Kingdom
Clinical Trial Site
🇬🇧
Leeds, United Kingdom
Covance Clinical Research Unit
🇬🇧
Leeds, United Kingdom