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

Paroxysmal Nocturnal Hemoglobinuria (PNH) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02352493
• Other study ID #: ALN-CC5-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2015
• Est. completion date: August 2017

Study information

• Verified date: March 2020
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: August 2017
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention

Drug:
• ALN-CC5
Single or multiple doses of ALN-CC5 by subcutaneous (sc) injection
• Sterile Normal Saline (0.9% NaCl)
calculated volume to match active comparator

Locations

Country	Name	City	State
Spain	Clinical Trial Site	Barcelona
United Kingdom	Clinical Trial Site	Leeds
United Kingdom	Covance Clinical Research Unit	Leeds
United Kingdom	Richmond Pharmacology	London

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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