Table 2.

AAV hemophilia B clinical trials under the control of a liver-specific promoter.

Sponsor (ID)	Phase	Serotype	Cell Line	Transgene	Dose (vg/kg)	Enrolled n (planned)	FIX:C∞ (median)	# with ↑ ALT	Follow-up (years)	NCT Number
Avigen/CHOP	I/II	AAV2	Mammalian	F9-WT	8 × 1010	2	< 1	0/2	12–15	00076557
					4 × 1011	3	< 1	1/3
					2 × 1012	2	< 1	1/2
SJCRH/UCL	I	AAV8	Mammalian	co-sc-F9-WT	2 × 1011	2	1.4–2.2	0/2	8	00979238
					6 × 1011	2	2.1–2.9	0/2
					2 × 1012	6	2.9–7.2	4/6
uniQure (AMT-060)	I/II	AAV5	Insect	coF9-WT	5 × 1012	5	1.3–8.2 (5.3)	1/5	4	02396342
					2 × 1013	5	3.9–11.1 (7.1)	2/5
Spark (“Spark-9001”)	I/II	Spark-100	Mammalian	coF9-Padua	5 × 1011	10	14–81 (29.5)	2/10	> 3	02484092
Shire (“BAX 335”)	I/II	AAV8	Mammalian	co-sc-F9-Padua	2 × 1011	2	3.5*	NA	> 2.5	01687608
					1 × 1012	4	12.0*	NA
					3 × 1012	2	45*	2/4
Uniqure (AMT-061)	IIb	AAV5	Insect	coF9-Padua	2 × 1013	3	31.3–50.2 (40.8)	0/3	1–2	03489291△
Freeline (“FLT180a”)	I/II	AAVS3	Mammalian	coF9-Padua	4.5 × 1011	2	37–38	0/2	2	03369444
					7.5 × 1011	2	2–60	2/2φ	1
					9.75 × 1011	4	57–139	1/2φ	< 1
					1.5 × 1012	2	90–253	2/2φ	< 1
Dimension (“DTX 101”)	I/II	AAVrh10	Mammalian	coF9-WT	1.6 × 1012	3	1.67	NA	< 1	02618915
					5 × 1012	3	22.47	3/3<

^∞last available reported data, aPTT based clot assay values;

^*median peak FIX values, only two patients with sustained FIX activity beyond 1 year[50];

^φpatients required additional immunosuppression despite prophylactic steroids;

^△trial includes patients with neutralizing antibodies to AAV5

AAV, adeno-associated virus; ALT, alanine aminotransferase; co, codon-optimized; FIX, factor IX; NA: not available, NCT, national clinical trials; SJCRH, St. Jude Children’s Research Hospital; UCL, University College of London