PRIMA
(2013)Objective
To evaluate the efficacy and safety of Privigen (10% liquid IVIG stabilized with L-proline) for induction and maintenance treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP)
Study Summary
• IVIG-pretreated patients showed higher response (76.9%) than IVIG-naïve patients (46.7%)
• Improvements sustained across all secondary endpoints including grip strength and MRC sum score
Intervention
Privigen induction dose 2 g/kg body weight over 2-5 days, followed by up to 7 maintenance doses of 1 g/kg at 3-week intervals
Inclusion Criteria
Adults ≥18 years with definite or probable CIDP per EFNS/PNS guidelines; IVIG-naïve patients with progressive disease or IVIG-pretreated patients who deteriorated ≥1 INCAT point during washout
Study Design
Arms: Single-arm (Privigen IVIG), no control group; historical comparison to ICE study placebo arm
Patients per Arm: 28 enrolled, 25 completed
Outcome
• Median INCAT score improved from 3.5 to 2.5 points; median MRC sum score improved from 67.0 to 75.5 points
• Two serious adverse events of hemolysis during induction phase led to treatment discontinuation; both resolved without sequelae
Bottom Line
Privigen demonstrated efficacy in CIDP with a 60.7% responder rate based on adjusted INCAT score improvement, exceeding the predefined success threshold. IVIG-pretreated patients showed higher response rates than IVIG-naïve patients. Treatment was generally well-tolerated, though two cases of hemolysis during induction led to discontinuation.
Major Points
- Single-arm, open-label Phase III study using historical control comparison to ICE study placebo arm
- Primary endpoint met: 60.7% responder rate (95% CI: 42.4-76.4%) exceeded the predefined threshold of >35%
- IVIG-pretreated patients had higher responder rate (76.9%) than IVIG-naïve patients (46.7%)
- Of the 18 patients who ever responded, half (9/18) responded by Week 4 after induction and 16/18 responded by Week 10
- Median time to first INCAT response: 3 weeks for IVIG-pretreated vs. 18 weeks for IVIG-naïve patients
- Consistent improvements across all secondary endpoints: INCAT score, grip strength, and MRC sum score
- MRC-based responder rate was 82.1% (23/28 patients)
- Two serious adverse events of hemolysis during induction phase in patients with non-O blood groups
- Both hemolysis cases resolved after treatment discontinuation without need for transfusion
- Study suggests patients not responding by 6 weeks may still respond with continued treatment
Study Design
- Study Type
- Prospective, multicenter, single-arm, open-label Phase III study
- Randomization
- No
- Blinding
- None (open-label)
- Sample Size
- 28
- Follow-up
- 25 weeks (induction plus up to 7 maintenance doses at 3-week intervals)
- Centers
- 13
- Countries
- Germany, Belgium, Poland, France, Finland
Primary Outcome
Definition: Responder rate by adjusted INCAT score at completion; responder defined as ≥1 point improvement; success criterion: lower limit of 95% CI >35% (based on ICE study placebo arm)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - | - | - (42.41-76.43%) | Met success criterion (lower CI 42.4% > 35%) |
Limitations & Criticisms
- Single-arm design without concurrent control group limits causal inference
- Historical control comparison to ICE study placebo arm rather than randomized comparison
- Small sample size (n=28) limits generalizability
- Open-label design introduces potential bias in outcome assessment
- Success criterion based on historical data from different IVIG product
- Mixed population of IVIG-pretreated and IVIG-naïve patients complicates interpretation
- Washout design for IVIG-pretreated patients may have selected for treatment-dependent patients
- Short follow-up (25 weeks) does not assess long-term durability
- Higher responder rate in pretreated patients may reflect selection bias
- Two hemolysis SAEs highlight safety concerns with high-dose IVIG induction
Citation
J Peripher Nerv Syst 2013;18:130-140