Clinical trial NCT02352493: A Phase 1/2 Study of an Investigational Drug, ALN-CC5, in Healthy Adult Volunteers and Patients With PNH
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: PNH
RNAi therapeutic
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-02-02
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Part A: through day 658; Part B: through day 532; Part C: through day 280
Secondary outcomes:
measure: Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Alternative Pathway (CAP)
timeFrame: Part A: through day 70; Part B: through day 140; Part C: through day 140
measure: Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Classical Pathway (CCP)
timeFrame: Part A: through day 70; Part B: through day 140; Part C: through day 140
measure: Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in C5 Protein Levels
timeFrame: Part A: through day 70; Part B: through day 140; Part C: through day 140
measure: Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (25-mer)
timeFrame: 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
measure: Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (23-mer)
timeFrame: 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
measure: Pharmacokinetic (PK) Effect of ALN-CC5: T Max (25-mer)
timeFrame: 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
measure: Pharmacokinetic (PK) Effect of ALN-CC5: T Max (23-mer)
timeFrame: 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
measure: Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (25-mer)
timeFrame: 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
measure: Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (23-mer)
timeFrame: 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
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Leeds
country: United Kingdom
facility: Clinical Trial Site
city: Leeds
country: United Kingdom
facility: Covance Clinical Research Unit
city: London
country: United Kingdom
facility: Richmond Pharmacology
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Nader Najafian, MD
role: STUDY_DIRECTOR
References:
citation: Badri P, Jiang X, Borodovsky A, Najafian N, Kim J, Clausen VA, Goel V, Habtemariam B, Robbie GJ. Pharmacokinetic and Pharmacodynamic Properties of Cemdisiran, an RNAi Therapeutic Targeting Complement Component 5, in Healthy Subjects and Patients with Paroxysmal Nocturnal Hemoglobinuria. Clin Pharmacokinet. 2021 Mar;60(3):365-378. doi: 10.1007/s40262-020-00940-9.